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Engineered Mycobacterium tuberculosis antigen assembly into core-shell nanobeads for diagnosis of tuberculosis

Sheffee NS, Rubio-Reyes P, Mirabal M, Calero R, Carrillo-Calvet H, Chen S, et al.

Nanomedicine, 2021 06;34:102374.
PMID: 33675981 DOI: 10.1016/j.nano.2021.102374

Despite recent advances in diagnosis, tuberculosis (TB) remains one of the ten leading causes of death worldwide. Here, we engineered Mycobacterium tuberculosis (Mtb) proteins (ESAT6, CFP10, and MTB7.7) to self-assemble into core-shell nanobeads for enhanced TB diagnosis. Respective purified Mtb antigen-coated polyester beads were characterized and their functionality in TB diagnosis was tested in whole blood cytokine release assays. Sensitivity and specificity were studied in 11 pulmonary TB patients (PTB) and 26 healthy individuals composed of 14 Tuberculin Skin Test negative (TSTn) and 12 TST positive (TSTp). The production of 6 cytokines was determined (IFNγ, IP10, IL2, TNFα, CCL3, and CCL11). To differentiate PTB from healthy individuals (TSTp + TSTn), the best individual cytokines were IL2 and CCL11 (>80% sensitivity and specificity) and the best combination was IP10 + IL2 (>90% sensitivity and specificity). We describe an innovative approach using full-length antigens attached to biopolyester nanobeads enabling sensitive and specific detection of human TB.
Fulltext Enhanced Contextual Fear Memory and Elevated Astroglial Glutamate Synthase Activity in Hippocampal CA1 BChE shRNA Knockdown Mice

Chen S, Lin Z, Tan KL, Chen R, Su W, Zhao H, et al.

Front Psychiatry, 2020;11:564843.
PMID: 33061920 DOI: 10.3389/fpsyt.2020.564843

Butyrylcholinesterase (BChE) efficiently hydrolyzes acetylcholine (ACh) at high concentrations when acetylcholinesterase (AChE) is substrate-inhibited. Recent studies have shown that BChE also has a function that is independent of ACh, but it has not been fully explored. Low BChE expression is accompanied with higher stress-induced aggression and ghrelin levels in stress models, and BChE knockout mice exhibit cognitive and memory impairments. However, the role of BChE in posttraumatic stress disorder (PTSD) remains unclear. In the present study, we investigated the role of BChE in contextual fear memory and its regulatory effect on the expression of factors related to the glutamate (Glu)-glutamine (Gln) cycle via knockdown studies. We used AAVs and lentiviruses to knockdown BChE expression in the mouse hippocampal CA1 region and C8D1A astrocytes. Our behavioral data from those mice injected with AAV-shBChE in the hippocampal CA1 region showed strengthened fear memory and increased dendritic spine density. Elevated Glu levels and glutamine synthetase (GS) enzyme activity were detected in contextual fear conditioned-BChE knockdown animals and astrocytes. We observed that an AAV-shBChE induced lowering of BChE expression in the hippocampus CA1 region enhanced contextual fear memory expression and promoted the astrocytic Glu-Gln cycle but did not elevate ACh-hydrolyzing activity. This study provides new insight into the regulatory role of BChE in cognition and suggests potential target for stress-related psychiatric disorder such as PTSD where patients experience fear after exposure to severe life-threatening traumatic events.
Fulltext Estimating prevalence of subjective cognitive decline in and across international cohort studies of aging: a COSMIC study

Röhr S, Pabst A, Riedel-Heller SG, Jessen F, Turana Y, Handajani YS, et al.

Alzheimers Res Ther, 2020 12 18;12(1):167.
PMID: 33339532 DOI: 10.1186/s13195-020-00734-y

BACKGROUND: Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer's disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts.
METHODS: We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence.
RESULTS: The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3-24.4%) and IRT (25.6%, 95%CI = 25.1-26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1-7.0%, to 52.7%, 95%CI = 47.4-58.0%; IRT: 7.8%, 95%CI = 6.8-8.9%, to 52.7%, 95%CI = 47.4-58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades.
CONCLUSIONS: SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field.
Ethnic differences in the Goodenough-Harris draw-a-man and draw-a-woman tests

Dugdale AE, Chen ST

Arch Dis Child, 1979 Nov;54(11):880-5.
PMID: 393181

The draw-a-man (DAM) and draw-a-woman (DAW) tests were given to 307 schoolchildren in Petaling Jaya, Malaysia. The children were ethnically Malay, Chinese, or Indian (Tamil), and all came from lower socioeconomic groups. The standard scores of the Chinese children averaged 118 in the DAM and 112 in the DAW tests. These scores were significantly better than the American standards. Malay children scored significantly lower than Chinese, and Tamil children scored lower again. The nutritional status of the children had no influence on the scores. Chinese and Tamil children scored better in the DAM than the DAW, while in Malay boys the reverse was true. Malay children tended to emphasise clothing in the DAM, but Chinese and Tamil children scored better on items relating to facial features and body proportions. The Goodenough-Harris draw-a-person tests are obviously not culture-free, but the causes of ethnic differences have not been elucidated.
Evidence for the Higgs Boson Decay to a Z Boson and a Photon at the LHC

Aad G, Abbott B, Abeling K, Abicht NJ, Abidi SH, Aboulhorma A, et al.

Phys Rev Lett, 2024 Jan 12;132(2):021803.
PMID: 38277607 DOI: 10.1103/PhysRevLett.132.021803

The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140 fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.
Fulltext Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model

Botelho D, Leo BF, Massa C, Sarkar S, Tetley T, Chung KF, et al.

Front Pharmacol, 2018;9:213.
PMID: 29632485 DOI: 10.3389/fphar.2018.00213

Here we examine the organ level toxicology of both carbon black (CB) and silver nanoparticles (AgNP). We aim to determine metal-specific effects to respiratory function, inflammation and potential interactions with lung lining fluid (LLF). C57Bl6/J male mice were intratracheally instilled with saline (control), low (0.05 μg/g) or high (0.5 μg/g) doses of either AgNP or CB 15 nm nanospheres. Lung histology, cytology, surfactant composition and function, inflammatory gene expression, and pulmonary function were measured at 1, 3, and 7 days post-exposure. Acutely, high dose CB resulted in an inflammatory response, increased neutrophilia and cytokine production, without alteration in surfactant composition or respiratory mechanics. Low dose CB had no effect. Neither low nor high dose AgNPs resulted in an acute inflammatory response, but there was an increase in work of breathing. Three days post-exposure with CB, a persistent neutrophilia was noted. High dose AgNP resulted in an elevated number of macrophages and invasion of lymphocytes. Additionally, AgNP treated mice displayed increased expression of IL1B, IL6, CCL2, and IL10. However, there were no significant changes in respiratory mechanics. At day 7, inflammation had resolved in AgNP-treated mice, but tissue stiffness and resistance were significantly decreased, which was accompanied by an increase in surfactant protein D (SP-D) content. These data demonstrate that the presence of metal alters the response of the lung to nanoparticle exposure. AgNP-surfactant interactions may alter respiratory function and result in a delayed immune response, potentially due to modified airway epithelial cell function.
Expression and characterization of anticoagulant activity of salivary protein alALP from Asian tiger mosquito Aedes albopictus

Li XP, Lin D, Zhang Y, Chen SQ, Bai HQ, Zhang SN, et al.

Trop Biomed, 2020 Mar 01;37(1):116-126.
PMID: 33612723

Several bioactive molecules isolated from the saliva of blood-sucking arthropods, such as mosquitoes, have been shown to exhibit potential anticoagulant function. We have previously identified a 30kDa allergen named Aegyptin-like protein (alALP), which is highly homologous to Aegyptin, from the salivary glands of female Aedes albopictus (Asian tiger mosquito). In this study, we identified the conserved functional domain of alALP by using bioinformatic tools, and expressed the His-tagged alALP recombinant protein in sf9 insect cells by generation and transfection of a baculoviral expression plasmid carrying the fulllength cDNA of alALP. We purified this recombinant protein and examined its function on the inhibition of blood coagulation. The results showed that the purified His-alALP prolonged the Activated Partial Thromboplastin Time (APTT), Prothrombin Time (PT) and Thrombin Time (TT) in vitro as well as the Bleeding Time (BT) in vivo, which suggest that alALP could be a novel anticoagulant.
Feeding Artemia franciscana (Kellogg) larvae with bacterial heat shock protein, protects from Vibrio campbellii infection

Sung YY, Ashame MF, Chen S, Macrae TH, Sorgeloos P, Bossier P

J Fish Dis, 2009 Aug;32(8):675-85.
PMID: 19515074 DOI: 10.1111/j.1365-2761.2009.01046.x

Among their numerous physiological effects, heat shock proteins (Hsps) are potent immunomodulators, a characteristic reflecting their potential as therapeutic agents and which led to their application in combating infection. As an example, the up-regulation of endogenous Hsp70 in the branchiopod crustacean Artemia franciscana (Kellogg) is concurrent with shielding against bacterial infection. To better understand this protective mechanism, gnotobiotic Artemia were fed with Escherichia coli treated to over-produce different prokaryotic Hsps. This was shown to increase larval resistance to experimental Vibrio campbellii exposure. Immunoprobing of Western blots showed that the enhanced resistance to V. campbellii correlated with DnaK production in E coli. A definitive role for DnaK was then demonstrated by feeding Artemia larvae with transformed bacteria over-producing only this protein, although other Hsps such as DnaJ and grpE also provided tolerance against Vibrio infection. Feeding of bacteria synthesizing selected Hsps is therefore suggested as an alternative to antibiotic use as a means of enhancing resistance of Artemia larvae to bacterial infection, which may have potential applications in aquaculture.
First Report of Fruit Rot of Loquat Caused by an Alternaria sp. in Taiwan

Ko Y, Liu CW, Chen SS, Chen CY, Yao KS, Maruthasalam S, et al.

Plant Dis, 2010 Apr;94(4):481.
PMID: 30754488 DOI: 10.1094/PDIS-94-4-0481B

During March 2007, a fruit rot disease was observed in several loquat (Eriobotrya japonica (Thunberg) Lindley) fields located in Taichung, Nantou, and Miaoli counties. Loquat is a valuable fruit crop grown predominantly in central Taiwan, and hence, even a minor yield loss by this new disease is economically significant. Symptoms on fruits initially appeared as small lesions (<1 mm) that later developed into light-to-dark brown, circular, larger (7 mm), sunken lesions, indicating invasion of a pathogen into the fruit. Pieces of rotted fruit tissue (1 × 1 × 1 mm) were immersed for 1 min in 3% commercial bleach, followed by 70% ethanol, cultured on potato dextrose agar (PDA), and incubated under constant fluorescent light (185 ± 35 μE·m-2·s-1) at 24°C for 2 days. Three single conidial isolates (AS1 to AS3) were selected and used in morphological and pathogenicity studies. All three isolates were identified as an Alternaria sp. (1-3) and formed abundant, dark brown mycelium when cultured on PDA with light at 24°C. Conidiophores were 60 to 89 × 3 to 5 μm, densely fasciculate, cylindrical, simple or branched, and had distinct conidial scars. Conidia were 12 to 74 × 6 to 14 μm, golden brown, straight or curved, obclavate with beaks measuring half the length of the conidium, and observed in chains of 10 or more spores with four to seven transverse septa and several longitudinal septa. Pathogenicity tests were conducted twice by inoculating eight surface-sterilized wounded or unwounded fruits with each of the three isolates in each experiment. Two cuts (1 × 1 × 1 mm) were made on each fruit 3 cm apart with a sterile scalpel, and a 300-μl spore suspension (2 × 105 conidia per ml) was placed on each wound. Similarly, a 300-μl spore suspension was placed on unwounded fruits and air dried for 5 min. Control fruits were similarly treated with sterile water. Inoculated fruits were enclosed in a plastic bag and kept at 24 ± 1°C. Symptoms of soft rot were observed on 60% (unwounded) and 100% (wounded) of inoculated fruits 5 days after inoculation, while control fruits did not develop disease symptoms. Reisolation from the symptomatic fruits consistently yielded an Alternaria sp. This fungus previously has been reported as the causal agent of fruit rot or black spot of papaya, mango, kiwifruit, pear, and carambola from Australia, India, Malaysia, South Africa, and the United States (1-3). To our knowledge, this is the first report of fruit rot of loquat caused by an Alternaria sp. in Taiwan. To manage this disease, growers may resort to fungicidal sprays followed by bagging of fruits to reduce pre- and postharvest losses. References: (1) A. L. Jones and H. S. Aldwinckle. Compendium of Apple and Pear Diseases. The American Phytopathological Society. St. Paul, MN, 1990. (2) R. C. Ploetz. Diseases of Tropical Fruit Crops. CABI Publishing. Wallingford, Oxfordshire, UK, 2003. (3) R. C. Ploetz et al. Compendium of Tropical Fruit Diseases. The American Phytopathological Society. St. Paul, MN, 1994.
Frequent loss of CD10 expression in follicular lymphoma with leukaemic presentation

Chen SW, Chang ST, Hsieh YC, Kuo CC, Wu HC, Feng YH, et al.

Malays J Pathol, 2020 Aug;42(2):237-243.
PMID: 32860376

INTRODUCTION: Follicular lymphoma (FL) is usually a nodal lymphoma expressing CD10, rarely with leukaemic presentation (FL-LP).
MATERIALS AND METHODS: We searched for FL-LP in our institution from 2000 to 2018 and characterised the neoplastic cells by flow cytometry, immunohistochemistry and fluorescence in situ hybridization. Thirteen (6.1%) of 212 FL cases were FL-LP, all de novo neoplasms. The leukaemic cells were small in 12 cases and large in one. All had concurrent FL, mostly (92%; 12/13) low-grade. The single case with large leukaemic cells had a concurrent primary splenic low-grade FL and a double-hit large B-cell lymphoma in the marrow.
RESULTS: CD10 was expressed in the leukaemic cells in 38% (5/13) cases by flow cytometry and in 77% (10/13) cases in tumours (p= 0.0471). IGH/BCL2 reciprocal translocation was identified in 85% (11/13) cases. Most patients were treated with chemotherapy. In a median follow-up time of 36 months, nine patients were in complete remission. The 2- and 5-year survival rates were at 100% and 83%, respectively. In this study, we characterised a series of de novo FL-LP in Taiwan. All patients had concurrent nodal and/or tissue tumours, which might suggest that these patients seek medical help too late.
CONCLUSION: The lower CD10 expression rate by flow cytometry than by immunohistochemistry might be due to different epitopes for these assays. Alternatively, loss of CD10 expression might play a role in the pathogenesis of leukaemic change. The clinical course of FL-LP could be aggressive, but a significant proportion of the patients obtained complete remission with chemotherapy.
Fulltext Genetic Connections and Convergent Evolution of Tropical Indigenous Peoples in Asia

Deng L, Pan Y, Wang Y, Chen H, Yuan K, Chen S, et al.

Mol Biol Evol, 2022 Feb 03;39(2).
PMID: 34940850 DOI: 10.1093/molbev/msab361

Tropical indigenous peoples in Asia (TIA) attract much attention for their unique appearance, whereas their genetic history and adaptive evolution remain mysteries. We conducted a comprehensive study to characterize the genetic distinction and connection of broad geographical TIAs. Despite the diverse genetic makeup and large interarea genetic differentiation between the TIA groups, we identified a basal Asian ancestry (bASN) specifically shared by these populations. The bASN ancestry was relatively enriched in ancient Asian human genomes dated as early as ∼50,000 years before the present and diminished in more recent history. Notably, the bASN ancestry is unlikely to be derived from archaic hominins. Instead, we suggest it may be better modeled as a survived lineage of the initial peopling of Asia. Shared adaptations inherited from the ancient Asian ancestry were detected among the TIA groups (e.g., LIMS1 for hair morphology, and COL24A1 for bone formation), and they are enriched in neurological functions either at an identical locus (e.g., NKAIN3), or different loci in an identical gene (e.g., TENM4). The bASN ancestry could also have formed the substrate of the genetic architecture of the dark pigmentation observed in the TIA peoples. We hypothesize that phenotypic convergence of the dark pigmentation in TIAs could have resulted from parallel (e.g., DDB1/DAK) or genetic convergence driven by admixture (e.g., MTHFD1 and RAD18), new mutations (e.g., STK11), or notably purifying selection (e.g., MC1R). Our results provide new insights into the initial peopling of Asia and an advanced understanding of the phenotypic convergence of the TIA peoples.
Fulltext Genetic diversity of geographically distinct Streptococcus dysgalactiae isolates from fish

Abdelsalam M, Eissa AE, Chen SC

J Adv Res, 2015 Mar;6(2):233-8.
PMID: 25750757 DOI: 10.1016/j.jare.2013.12.003

Streptococcus dysgalactiae is an emerging pathogen of fish. Clinically, infection is characterized by the development of necrotic lesions at the caudal peduncle of infected fishes. The pathogen has been recently isolated from different fish species in many countries. Twenty S. dysgalactiae isolates collected from Japan, Taiwan, Malaysia and Indonesia were molecularly characterized by biased sinusoidal field gel electrophoresis (BSFGE) using SmaI enzyme, and tuf gene sequencing analysis. DNA sequencing of ten S. dysgalactiae revealed no genetic variation in the tuf amplicons, except for three strains. The restriction patterns of chromosomal DNA measured by BSFGE were differentiated into six distinct types and one subtype among collected strains. To our knowledge, this report gives the first snapshot of S. dysgalactiae isolates collected from different countries that are localized geographically and differed on a multinational level. This genetic unrelatedness among different isolates might suggest a high recombination rate and low genetic stability.
Fulltext Growth charts based on longitudinal study of Malaysian children from birth to six years

Chen ST

Med J Malaysia, 1985 Jun;40(2):80-9.
PMID: 3834290

Percentile growth charts of weight, length and head circumference, from birth to six years of age, for boys and girls, are presented. These can be used to monitor the growth of Malaysian children.
Growth of arm circumference and triceps skinfold of Malay children from birth to six years of age

Chen ST

J Singapore Paediatr Soc, 1990;32(3-4):87-96.
PMID: 2133762

126 Malaysian children, 65 boys and 61 girls from higher income families were followed-up regularly from birth to six years of age in the University Hospital, Kuala Lumpur. The study shows that for boys and girls, there is a progressive increase in the left mid-upper arm circumference from birth to six years of age. However the rate of growth is not even, being most rapid during the first four month of infancy, then rapidly decreases during the middle third of infancy and thereafter it decreases slowly and by the second year of life, there is hardly any increase in the arm circumference. The left triceps skinfold thickness curves for boys and girls rise rapidly after birth to reach a peak at about three to five months before commencing to decline and then flatten off from the second year of life. The study also shows that on the whole, boys have slightly bigger arm circumference than girls during the first two years of life. From two years of age, girls on the average have more fat than boys. However this difference is statistically not significant at the ages tested. This paper also presents the left mid-upper arm circumference and left triceps skinfold percentile charts of Malaysian boys and girls from birth to six years of age.
Growth of head circumference of Malaysian infants and pre-school children

Chen ST

J Singapore Paediatr Soc, 1990;32(3-4):81-6.
PMID: 2133761

126 Malaysian children, 65 boys and 61 girls from higher income families were followed-up regularly from birth to six years of age in the University Hospital, Kuala Lumpur. The study confirms the observations of previous studies that growth velocity of head circumference is most rapid during the first few months of infancy and then decreases so that by the fifth year of life the increment is minimal. It also confirms the fact that boys have bigger head circumferences than girls. The paper also presents the head circumference distance and velocity percentile charts which can be used to monitor the head circumference of Malaysian children.
Growth of weight, length and crown-rump length of Malaysian infants and pre-school children

Chen ST

J Singapore Paediatr Soc, 1990;32(3-4):65-80.
PMID: 2133760

126 Malaysian children, 65 boys and 61 girls from higher income families were followed-up regularly from birth to six years of age in the University Hospital, Kuala Lumpur. Their physical growth, development, dietary and illness patterns were measured at each visit. The study confirms the observations of previous studies that boys are, on the average, heavier and taller than girls and that Asians are smaller in size with relatively shorter legs compared with children of European ancestry. These racial differences are due to a combination of genetic and environmental differences. Since there are genetic differences in the size and shape of children, standards applicable to the specific population should be used to obtain the best results when assessing the health of an individual child. The growth charts presented in this paper can be used as standards to monitor the growth of Asian infants and pre-school children.
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.

Autophagy, 2016;12(1):1-222.
PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1

Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.

Autophagy, 2021 Jan;17(1):1-382.
PMID: 33634751 DOI: 10.1080/15548627.2020.1797280

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
Fulltext Head circumference of Malaysian school children

Chen ST

Med J Malaysia, 1985 Jun;40(2):90-4.
PMID: 3834291

Percentile head circumference charts, from six to eleven years of age, for boys and girls are presented. These can be used to monitor the head circumference of Malaysian children.
Heat stress reduces brown adipose tissue activity by exacerbating mitochondrial damage in type 2 diabetic mice

Lai P, Zhang L, Qiu Y, Ren J, Sun X, Zhang T, et al.

J Therm Biol, 2024 Jan;119:103799.
PMID: 38342042 DOI: 10.1016/j.jtherbio.2024.103799

Epidemiological evidence shows that diabetic patients are susceptible to high temperature weather, and brown adipose tissue (BAT) activity is closely related to type 2 diabetes (T2DM). Activation of BAT under cold stress helps improve T2DM. However, the impact of high temperature on the activity of BAT is still unclear. The study aimed to investigate the impact of heat stress on glucose and lipid metabolism in T2DM mice by influencing BAT activity. High-fat feeding and injecting streptozotocin (STZ) induced model of T2DM mice. All mice were randomly divided into three groups: a normal(N) group, a diabetes (DM) group and a heat stress diabetes (DMHS) group. The DMHS group received heat stress intervention for 3 days. Fasting blood glucose, fasting serum insulin and blood lipids were measured in all three groups. The activity of BAT was assessed by using quantitative real-time PCR (qRT-PCR), electron microscopy, and PET CT. Furthermore, the UHPLC-Q-TOF MS technique was employed to perform metabolomics analysis of BAT on both DM group and DMHS group. The results of this study indicated that heat stress aggravated the dysregulation of glucose and lipid metabolism, exacerbated mitochondrial dysfunction in BAT and reduced the activity of BAT in T2DM mice. This may be related to the abnormal accumulation of branched-chain amino acids (BCAAs) in the mitochondria of BAT.

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