Brown-fat-mediated tumour suppression by cold-altered global metabolism.

Glucose uptake is essential for cancer glycolysis and is involved in non-shivering thermogenesis of adipose tissues1-6. Most cancers use glycolysis to harness energy for their infinite growth, invasion and metastasis2,7,8. Activation of thermogenic metabolism in brown adipose tissue (BAT) by cold and drugs instigates blood glucose uptake in adipocytes4,5,9. However, the functional effects of the global metabolic changes associated with BAT activation on tumour growth are unclear. Here we show that exposure of tumour-bearing mice to cold conditions markedly inhibits the growth of various types of solid tumours, including clinically untreatable cancers such as pancreatic cancers. Mechanistically, cold-induced BAT activation substantially decreases blood glucose and impedes the glycolysis-based metabolism in cancer cells. The removal of BAT and feeding on a high-glucose diet under cold exposure restore tumour growth, and genetic deletion of Ucp1-the key mediator for BAT-thermogenesis-ablates the cold-triggered anticancer effect. In a pilot human study, mild cold exposure activates a substantial amount of BAT in both healthy humans and a patient with cancer with mitigated glucose uptake in the tumour tissue. These findings provide a previously undescribed concept and paradigm for cancer therapy that uses a simple and effective approach. We anticipate that cold exposure and activation of BAT through any other approach, such as drugs and devices either alone or in combination with other anticancer therapeutics, will provide a general approach for the effective treatment of various cancers.

Suppressing Zn pulverization with three-dimensional inert-cation diversion dam for long-life Zn metal batteries.

Tremendous attention has been paid to the water-associated side reactions and zinc (Zn) dendrite growth on the electrode-electrolyte interface. However, the Zn pulverization that can cause continuous depletion of active Zn metal and exacerbate hydrogen evolution is severely neglected. Here, we disclose that the excessive Zn feeding that causes incomplete crystallization is responsible for Zn pulverization formation through analyzing the thermodynamic and kinetics process of Zn deposition. On the basis, we introduce 1-ethyl-3-methylimidazolium cations (EMIm+) into the electrolyte to form a Galton-board-like three-dimensional inert-cation (3DIC) region. Modeling test shows that the 3DIC EMIm+ can induce the Zn2+ flux to follow in a Gauss distribution, thus acting as elastic sites to buffer the perpendicular diffusion of Zn2+ and direct the lateral diffusion, thus effectively avoiding the local Zn2+ accumulation and irreversible crystal formation. Consequently, anti-pulverized Zn metal deposition behavior is achieved with an average Coulombic efficiency of 99.6% at 5 mA cm-2 over 2,000 cycles and superb stability in symmetric cell over 1,200 h at -30 °C. Furthermore, the Zn||KVOH pouch cell can stably cycle over 1,200 cycles at 2 A g-1 and maintain a capacity of up to 12 mAh.

Quantitative assessment of near-infrared fluorescent proteins.

Recent progress in fluorescent protein development has generated a large diversity of near-infrared fluorescent proteins (NIR FPs), which are rapidly becoming popular probes for a variety of imaging applications. However, the diversity of NIR FPs poses a challenge for end-users in choosing the optimal one for a given application. Here we conducted a systematic and quantitative assessment of intracellular brightness, photostability, oligomeric state, chemical stability and cytotoxicity of 22 NIR FPs in cultured mammalian cells and primary mouse neurons and identified a set of top-performing FPs including emiRFP670, miRFP680, miRFP713 and miRFP720, which can cover a majority of imaging applications. The top-performing proteins were further validated for in vivo imaging of neurons in Caenorhabditis elegans, zebrafish, and mice as well as in mice liver. We also assessed the applicability of the selected NIR FPs for multicolor imaging of fusions, expansion microscopy and two-photon imaging.

KRAS mutation-driven angiopoietin 2 bestows anti-VEGF resistance in epithelial carcinomas.

Defining reliable surrogate markers and overcoming drug resistance are the most challenging issues for improving therapeutic outcomes of antiangiogenic drugs (AADs) in cancer patients. At the time of this writing, no biomarkers are clinically available to predict AAD therapeutic benefits and drug resistance. Here, we uncovered a unique mechanism of AAD resistance in epithelial carcinomas with KRAS mutations that targeted angiopoietin 2 (ANG2) to circumvent antivascular endothelial growth factor (anti-VEGF) responses. Mechanistically, KRAS mutations up-regulated the FOXC2 transcription factor that directly elevated ANG2 expression at the transcriptional level. ANG2 bestowed anti-VEGF resistance as an alternative pathway to augment VEGF-independent tumor angiogenesis. Most colorectal and pancreatic cancers with KRAS mutations were intrinsically resistant to monotherapies of anti-VEGF or anti-ANG2 drugs. However, combination therapy with anti-VEGF and anti-ANG2 drugs produced synergistic and potent anticancer effects in KRAS-mutated cancers. Together, these data demonstrate that KRAS mutations in tumors serve as a predictive marker for anti-VEGF resistance and are susceptible to combination therapy with anti-VEGF and anti-ANG2 drugs.

Generation of mega brown adipose tissue in adults by controlling brown adipocyte differentiation in vivo.

Brown adipose tissue (BAT) is a highly specialized adipose tissue in its immobile location and size during the entire adulthood. In response to cold exposure and other ß3-adrenoreceptor stimuli, BAT commits energy consumption by nonshivering thermogenesis (NST). However, the molecular machinery in controlling the BAT mass in adults is unknown. Here, we show our surprising findings that the BAT mass and functions can be manipulated in adult animals by controlling BAT adipocyte differentiation in vivo. Platelet-derived growth factor receptor α (PDGFα) expressed in BAT progenitor cells served a signaling function to avert adipose progenitor differentiation. Genetic and pharmacological loss-of-function of PDGFRα eliminated the differentiation barrier and permitted progenitor cell differentiation to mature and functional BAT adipocytes. Consequently, an enlarged BAT mass (megaBAT) was created by PDGFRα inhibition owing to increases of brown adipocyte numbers. Under cold exposure, a microRNA-485 (miR-485) was identified as a master suppressor of the PDGFRα signaling, and delivery of miR-485 also produced megaBAT in adult animals. Noticeably, megaBAT markedly improved global metabolism, insulin sensitivity, high-fat-diet (HFD)-induced obesity, and diabetes by enhancing NST. Together, our findings demonstrate that the adult BAT mass can be increased by blocking the previously unprecedented inhibitory signaling for BAT progenitor cell differentiation. Thus, blocking the PDGFRα for the generation of megaBAT provides an attractive strategy for treating obesity and type 2 diabetes mellitus (T2DM).

Targeting adenosine A2A receptors for early intervention of retinopathy of prematurity.

Retinopathy of prematurity (ROP) continues to pose a significant threat to the vision of numerous children worldwide, primarily owing to the increased survival rates of premature infants. The pathologies of ROP are mainly linked to impaired vascularization as a result of hyperoxia, leading to subsequent neovascularization. Existing treatments, including anti-vascular endothelial growth factor (VEGF) therapies, have thus far been limited to addressing pathological angiogenesis at advanced ROP stages, inevitably leading to adverse side effects. Intervention to promote physiological angiogenesis during the initial stages could hold the potential to prevent ROP. Adenosine A2A receptors (A2AR) have been identified in various ocular cell types, exhibiting distinct densities and functionally intricate connections with oxygen metabolism. In this review, we discuss experimental evidence that strongly underscores the pivotal role of A2AR in ROP. In particular, A2AR blockade may represent an effective treatment strategy, mitigating retinal vascular loss by reversing hyperoxia-mediated cellular proliferation inhibition and curtailing hypoxia-mediated neovascularization in oxygen-induced retinopathy (OIR). These effects stem from the interplay of endothelium, neuronal and glial cells, and novel molecular pathways (notably promoting TGF-ß signaling) at the hyperoxia phase. We propose that pharmacological targeting of A2AR signaling may confer an early intervention for ROP with distinct therapeutic benefits and mechanisms than the anti-VEGF therapy.

Assessing the Content and Effect of Web-Based Decision Aids for Postmastectomy Breast Reconstruction: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Web-based decision aids have been shown to have a positive effect when used to improve the quality of decision-making for women facing postmastectomy breast reconstruction (PMBR). However, the existing findings regarding these interventions are still incongruent, and the overall effect is unclear. OBJECTIVE: We aimed to assess the content of web-based decision aids and its impact on decision-related outcomes (ie, decision conflict, decision regret, informed choice, and knowledge), psychological-related outcomes (ie, satisfaction and anxiety), and surgical decision-making in women facing PMBR. METHODS: This systematic review and meta-analysis followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 6 databases, PubMed, Embase, Cochrane Library, CINAHL, PsycINFO, and Web of Science Core Collection, were searched starting at the time of establishment of the databases to May 2023, and an updated search was conducted on April 1, 2024. MeSH (Medical Subject Headings) terms and text words were used. The Cochrane Risk of Bias Tool for randomized controlled trials was used to assess the risk of bias. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: In total, 7 studies included 579 women and were published between 2008 and 2023, and the sample size in each study ranged from 26 to 222. The results showed that web-based decision aids used audio and video to present the pros and cons of PMBR versus no PMBR, implants versus flaps, and immediate versus delayed PMBR and the appearance and feel of the PMBR results and the expected recovery time with photographs of actual patients. Web-based decision aids help improve PMBR knowledge, decisional conflict (mean difference [MD]=-5.43, 95% CI -8.87 to -1.99; P=.002), and satisfaction (standardized MD=0.48, 95% CI 0.00 to 0.95; P=.05) but have no effect on informed choice (MD=-2.80, 95% CI -8.54 to 2.94; P=.34), decision regret (MD=-1.55, 95% CI -6.00 to 2.90 P=.49), or anxiety (standardized MD=0.04, 95% CI -0.50 to 0.58; P=.88). The overall Grading of Recommendations, Assessment, Development, and Evaluation quality of the evidence was low. CONCLUSIONS: The findings suggest that the web-based decision aids provide a modern, low-cost, and high dissemination rate effective method to promote the improved quality of decision-making in women undergoing PMBR. TRIAL REGISTRATION: PROSPERO CRD42023450496; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=450496.

Research advances in microfluidic collection and detection of virus, bacterial, and fungal bioaerosols.

Bioaerosols are airborne suspensions of fine solid or liquid particles containing biological substances such as viruses, bacteria, cellular debris, fungal spores, mycelium, and byproducts of microbial metabolism. The global Coronavirus disease 2019 (COVID-19) pandemic and the previous emergence of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and influenza have increased the need for reliable and effective monitoring tools for bioaerosols. Bioaerosol collection and detection have aroused considerable attention. Current bioaerosol sampling and detection techniques suffer from long response time, low sensitivity, and high costs, and these drawbacks have forced the development of novel monitoring strategies. Microfluidic technique is considered a breakthrough for high performance analysis of bioaerosols. In recent years, several emerging methods based on microfluidics have been developed and reported for collection and detection of bioaerosols. The unique advantages of microfluidic technique have enabled the integration of bioaerosol collection and detection, which has a higher efficiency over conventional methods. This review focused on the research progress of bioaerosol collection and detection methods based on microfluidic techniques, with special attention on virus aerosols and bacterial aerosols. Different from the existing reviews, this work took a unique perspective of the targets to be collected and detected in bioaerosols, which would provide a direct index of bioaerosol categories readers may be interested in. We also discussed integrated microfluidic monitoring system for bioaerosols. Additionally, the application of bioaerosol detection in biomedicine was presented. Finally, the current challenges in the field of bioaerosol monitoring are presented and an outlook given of future developments.

Effectiveness of shared decision-making for mode of delivery after caesarean section: A systematic review and meta-analysis of randomized controlled trials.

AIM: To review the content, format and effectiveness of shared decision-making interventions for mode of delivery after caesarean section for pregnant women. DESIGN: Systematic review and meta-analysis. METHODS: Six databases (PubMed, Web of science Core Collection, Cochrance Network, Embase, CINAHL, PsycINFO) were searched starting at the time of establishment of the database to May 2023. Following the PRISMAs and use Review Manager 5.3 software for meta-analysis. Two review authors independently assessed the quality of the studies using the risk of bias 2 tool. The protocol was registered in PROSPERO (CRD42023410536). RESULTS: The search strategy obtained 1675 references. After abstract and full text screening, a total of seven studies were included. Shared decision-making interventions include decision aids and counselling that can help pregnant women analyse the pros and cons of various options and help them make decisions that are consistent with their values. The pooled results showed that shared decision-making intervention alleviated decisional conflicts regarding mode of delivery after caesarean section, but had no effect on knowledge and informed choice. CONCLUSION: The results of our review suggest that shared decision-making is an effective intervention to improve the quality of decision-making about the mode of delivery of pregnant women after caesarean section. However, due to the low quality of the evidence, it is recommended that more studies be conducted in the future to improve the quality of the evidence. CORRELATION WITH CLINICAL PRACTICE: This systematic review and meta-analysis provides evidence for the effectiveness of shared decision-making for mode of delivery after cesarean section and may provide a basis for the development of intervention to promote the participation of pregnant women in the decision-making process.

Genome-Wide Identification, Characterization and Experimental Expression Analysis of CNGC Gene Family in Gossypium.

Cyclic nucleotide-gated ion channels (CNGCs) are channel proteins for calcium ions, and have been reported to play important roles in regulating survival and environmental response of various plants. However, little is known about how the CNGC family works in Gossypium. In this study, 173 CNGC genes, which were identified from two diploid and five tetraploid Gossypium species, were classified into four groups by phylogenetic analysis. The collinearity results demonstrated that CNGC genes are integrally conservative among Gossypium species, but four gene losses and three simple translocations were detected, which is beneficial to analyzing the evolution of CNGCs in Gossypium. The various cis-acting regulatory elements in the CNGCs' upstream sequences revealed their possible functions in responding to multiple stimuli such as hormonal changes and abiotic stresses. In addition, expression levels of 14 CNGC genes changed significantly after being treated with various hormones. The findings in this study will contribute to understanding the function of the CNGC family in cotton, and lay a foundation for unraveling the molecular mechanism of cotton plants' response to hormonal changes.

Microfluidic Preparation of pH-Responsive Microsphere Fibers and Their Controlled Drug Release Properties.

In this study, a capillary microfluidic device was constructed, and sodium alginate solution and a pH-sensitive hydrophobic polymer (p(BMA-co-DAMA-co-MMA)) solution were introduced into the device for the preparation of hydrogel fibers loaded with polymer microspheres. The structure of the microsphere fiber, including the size and spacing of the microspheres, could be controlled by flow rate, and the microspheres were able to degrade and release cargo responding to acidic pH conditions. By modification with carboxymethylcellulose (CMC), alginate hydrogel exhibited enhanced pH sensitivity (shrunk in acidic while swollen in basic condition). This led to an impact on the diffusion rate of the molecules released from the inner microspheres. The microsphere fiber showed dramatic and negligible degradation and drug release in tumor cell (i.e., A431 and A549 cells) and normal cell environments, respectively. These results indicated that the microsphere fiber prepared in this study showed selective drug release in acidic environments, such as tumor and inflammation sites, which could be applied as a smart surgical dressing with normal tissue protective properties.

Inflammatory cell-derived CXCL3 promotes pancreatic cancer metastasis through a novel myofibroblast-hijacked cancer escape mechanism.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy and lacks effective treatment. We aimed to understand molecular mechanisms of the intertwined interactions between tumour stromal components in metastasis and to provide a new paradigm for PDAC therapy. DESIGN: Two unselected cohorts of 154 and 20 patients with PDAC were subjected to correlation between interleukin (IL)-33 and CXCL3 levels and survivals. Unbiased expression profiling, and genetic and pharmacological gain-of-function and loss-of-function approaches were employed to identify molecular signalling in tumour-associated macrophages (TAMs) and myofibroblastic cancer-associated fibroblasts (myoCAFs). The role of the IL-33-ST2-CXCL3-CXCR2 axis in PDAC metastasis was evaluated in three clinically relevant mouse PDAC models. RESULTS: IL-33 was specifically elevated in human PDACs and positively correlated with tumour inflammation in human patients with PDAC. CXCL3 was highly upregulated in IL-33-stimulated macrophages that were the primary source of CXCL3. CXCL3 was correlated with poor survival in human patients with PDAC. Mechanistically, activation of the IL-33-ST2-MYC pathway attributed to high CXCL3 production. The highest level of CXCL3 was found in PDAC relative to other cancer types and its receptor CXCR2 was almost exclusively expressed in CAFs. Activation of CXCR2 by CXCL3 induced a CAF-to-myoCAF transition and α-smooth muscle actin (α-SMA) was uniquely upregulated by the CXCL3-CXCR2 signalling. Type III collagen was identified as the CXCL3-CXCR2-targeted adhesive molecule responsible for myoCAF-driven PDAC metastasis. CONCLUSIONS: Our work provides novel mechanistic insights into understanding PDAC metastasis by the TAM-CAF interaction and targeting each of these signalling components would provide an attractive and new paradigm for treating pancreatic cancer.

Genome-wide identification of quantitative trait loci for morpho-agronomic and yield-related traits in foxtail millet (Setaria italica) across multi-environments.

Foxtail millet (Setaria italica) is an ideal model of genetic system for functional genomics of the Panicoideae crop. Identification of QTL responsible for morpho-agronomic and yield-related traits facilitates dissection of genetic control and breeding in cereal crops. Here, based on a Yugu1 × Longgu7 RIL population and genome-wide resequencing data, an updated linkage map harboring 2297 bin and 74 SSR markers was constructed, spanning 1315.1 cM with an average distance of 0.56 cM between adjacent markers. A total of 221 QTL for 17 morpho-agronomic and yield-related traits explaining 5.5 ~ 36% of phenotypic variation were identified across multi-environments. Of these, 109 QTL were detected in two to nine environments, including the most stable qLMS6.1 harboring a promising candidate gene Seita.6G250500, of which 70 were repeatedly identified in different trials in the same geographic location, suggesting that foxtail millet has more identical genetic modules under the similar ecological environment. One hundred-thirty QTL with overlapping intervals formed 22 QTL clusters. Furthermore, six superior recombinant inbred lines, RIL35, RIL48, RIL77, RIL80, RIL115 and RIL125 with transgressive inheritance and enrichment of favorable alleles in plant height, tiller, panicle morphology and yield related-traits were screened by hierarchical cluster. These identified QTL, QTL clusters and superior lines lay ground for further gene-trait association studies and breeding practice in foxtail millet.

Choroid plexus-selective inactivation of adenosine A2A receptors protects against T cell infiltration and experimental autoimmune encephalomyelitis.

BACKGROUND: Multiple sclerosis (MS) is one of the most common autoimmune disorders characterized by the infiltration of immune cells into the brain and demyelination. The unwanted immunosuppressive side effect of therapeutically successful natalizumab led us to focus on the choroid plexus (CP), a key site for the first wave of immune cell infiltration in experimental autoimmune encephalomyelitis (EAE), for the control of immune cells trafficking. Adenosine A2A receptor (A2AR) is emerging as a potential pharmacological target to control EAE pathogenesis. However, the cellular basis for the A2AR-mediated protection remains undetermined. METHODS: In the EAE model, we assessed A2AR expression and leukocyte trafficking determinants in the CP by immunohistochemistry and qPCR analyses. We determined the effect of the A2AR antagonist KW6002 treatment at days 8-12 or 8-14 post-immunization on T cell infiltration across the CP and EAE pathology. We determined the critical role of the CP-A2AR on T cell infiltration and EAE pathology by focal knock-down of CP-A2AR via intracerebroventricular injection of CRE-TAT recombinase into the A2ARflox/flox mice. In the cultured CP epithelium, we also evaluated the effect of overexpression of A2ARs or the A2AR agonist CGS21680 treatment on the CP permeability and lymphocytes migration. RESULTS: We found the specific upregulation of A2AR in the CP associated with enhanced CP gateway activity peaked at day 12 post-immunization in EAE mice. Furthermore, the KW6002 treatment at days 8-12 or 8-14 post-immunization reduced T cell trafficking across the CP and attenuated EAE pathology. Importantly, focal CP-A2AR knock-down attenuated the pathogenic infiltration of Th17+ cells across the CP via inhibiting the CCR6-CCL20 axis through NFκB/STAT3 pathway and protected against EAE pathology. Lastly, activation of A2AR in the cultured epithelium by A2AR overexpression or CGS21680 treatment increased the permeability of the CP epithelium and facilitated lymphocytes migration. CONCLUSION: These findings define the CP niche as one of the primary sites of A2AR action, whereby A2AR antagonists confer protection against EAE pathology. Thus, pharmacological targeting of the CP-A2AR represents a novel therapeutic strategy for MS by controlling immune cell trafficking across CP.

Non-coding RNAs in polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: Genetic, environmental and epigenetical factors may play important roles in the pathogenesis of polycystic ovary syndrome (PCOS), however the etiology of PCOS remains unclear. Studies indicated that non-coding RNAs (ncRNAs) were involved in the occurrence and development of PCOS. Thus, we aim to perform a systematic review and meta-analysis to investigate the presence and dysregulated expression of ncRNAs in human PCOS. METHODS: We searched in PubMed, Medline, Web of Science and Embase until July 2019 and summarized all eligible publications focusing on microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and small interfering RNAs (siRNAs) in PCOS. RESULTS: Sixty-seven articles were included in our systematic review and 9 articles were included in meta-analysis. There is little overlap between studies when comparing miRNA profiles. Sensitivity analysis showed that the expression of miR-93 was upregulated in PCOS patients (WMD 0.75, P < 0.00001), without heterogeneity among remaining studies (I2 = 0%). CONCLUSION: A large number of ncRNAs with altered levels were observed in plasma, serum, follicular fluid, granulosa cells or other issues from PCOS patients. Aberrant ncRNAs expression in PCOS may lead to aberrant steroidogenesis, adipocyte dysfunction, altered ovarian cell proliferation and/or apoptosis and have the potential to be used as diagnostic biomarkers.

Amino Acids in the Nutrition and Production of Sheep and Goats.

In sheep and goats, amino acid nutrition is essential for the maintenance of health and productivity. In this review, we analysed literature, mostly from the past two decades, focusing on assessment of amino acid requirements, especially on the balance of amino acid profiles between ruminal microbial protein and animal production protein (foetal growth, body weight gain, milk and wool). Our aim was to identify amino acids that might limit genetic potential for production. We propose that much attention should be paid to amino acid nutrition of individuals with greater abilities to produce meat, milk or wool, or to nourish large litters. Moreover, research is warranted to identify interactions among amino acids, particularly these amino acids that can send positive and negative signals at the same time.

Analysis of Differentially Expressed Genes of Chrysoperla sinica Related to Flight Capacity by Transcriptome.

The lacewing Chrysoperla sinica (Tjeder) is a common natural enemy of many insect pests in China and is frequently employed for biological control programs. Adults make migratory flights after emergence, which reduces their effectiveness as biological control agents. Previously, we proved that 2-d-old unmated females exhibited significantly stronger flight ability than 3-d-old ones. Meanwhile, 3-d-old unmated adults flew significantly longer distances than mated ones. In this study, Illumina RNA sequencing was performed to characterize differentially expressed genes (DEGs) between virgin and mated adults of different ages in a single female strain of C. sinica. In total, 713,563,726 clean reads were obtained and de novo assembled into 109,165 unigenes with an average length of 847 bp (N50 of 1,754 bp), among which 4,382 (4.01%) unigenes matched known proteins. Based on these annotations, many putative transcripts were related to C. sinica's flight capacity and muscle structure, energy supply, growth, development, environmental adaptability, and metabolism of nutritional components and bioactive components. In addition, the differential expression of transcripts between different ages and mating status were analyzed, and DEGs participating in flight capacity and muscles were detected, including glutathione hydrolase, NAD-specific glutamate dehydrogenase, aminopeptidase, and acidic amino acid decarboxylase. The DEGs with functions associated with flight capacity and muscles exhibited higher transcript levels for younger (2 d--old) virgins. This comprehensive C. sinica transcriptomic data provide a foundation for a better understanding of the molecular mechanisms underlying the flight capacity to meet the physiological demands of flight muscles in C. sinica.

2,3,5,6-Tetramethylpyrazine improves diet-induced whole-body insulin resistance via suppressing white adipose tissue lipolysis in mice.

Ectopic lipid accumulation in skeletal muscle and liver arises when nutrient storage systems are exposed to chronic energy surplus, leading to whole-body insulin resistance and metabolic disorders. One recent study has shown 2,3,5,6-tetramethylpyrazine (TMP), highly enriched in roasted foodstuffs, such as cocoa and peanuts, significantly decreases blood lipids levels and ameliorates ApoE-defect induced atherosclerosis suggesting a potent role of TMP in lipid dysregulation improvement. Here, we evaluated the impact of TMP treatment on high fat diet (HFD)-induced insulin resistance. Using hyperinsulinemic-euglycemic mouse clamp, we demonstrated 4-week TMP treatment improved whole-body insulin resistance in HFD-fed mice through suppressing lipolysis in white adipose tissue associated with reduced triglyceride in liver and improved glucose uptake in skeletal muscle. Collectively, our work provides proof-of-concept data to support the development of white adipose tissue-targeted medicine for the treatment of metabolic disorder.

EtMIC3 and its receptors BAG1 and ENDOUL are essential for site-specific invasion of Eimeria tenella in chickens.

Avian coccidian parasites exhibit a high degree of site specificity in different Eimeria species. Although the underlying mechanism is unclear, an increasing body of evidence suggests that site specificity is due to the interaction between microneme proteins (MICs) and their receptors on the surface of target host cells. In this study, the binding ability of E. tenella MICs (EtMICs) to different intestinal tissue was observed by immunofluorescence to identify the key surface molecule on the parasite responsible for the site specificity. Subsequently, we identified the corresponding host-cell receptors by yeast two-hybrid screening and glutathione-S-transferase pull-down experiments and the distribution of these receptors was observed by immunofluorescence in chicken intestinal tissues. Finally, we evaluated the efficacy of receptor antiserum against the infection of E. tenella in chickens. The results showed that EtMIC3 could only bind to the caecum while EtMIC1, EtMIC2, and EtAMA1 did not bind to any other intestinal tissues. Anti-serum to EtMIC3 was able to block the invasion of sporozoites with a blocking rate of 66.3%. The receptors for EtMIC3 were BCL2-associated athanogene 1 (BAG1) and Endonuclease polyU-specific-like (ENDOUL), which were mainly distributed in the caecum. BAG1 and ENDOUL receptor antiserum reduced weight loss and oocyst output following E. tenella infection, showing partial inhibition of E. tenella infection. These data elucidate the mechanism of site specificity for Eimeria infection and reveal a potential therapeutic avenue.

Risk and protective factors for burnout among physicians from standardized residency training programs in Shanghai: a cross-sectional study.

BACKGROUND: High burnout has been reported in physician populations. Although the standardized residency training (SRT) in China includes components that might put residents at a higher risk for burnout, the burnout of Chinese medical residents is unknown. This study aimed to evaluate the prevalence of burnout and the associated risk and protective factors for medical residents in the SRT program in Shanghai, China. METHODS: This study was a prospective cross-sectional design. A random sampling strategy was used to recruit 330 resident physicians from four SRT sites in Shanghai, and 318 completed questionnaires were returned. Respondents completed a self-made questionnaire including demographic and work characteristics, four burnout and wellness-specific surveys. Bivariate analyses and hierarchical multiple regression models were used to analyze factors associated with three sub-scales of burn out separately. RESULTS: The overall burnout rate was 71.4%. Low level rate of personal accomplishment (PA) was extremely high at 69.5%. Night shift experience, high occupational stress, and low social support were significant predictors, which explained 49.1% variance of emotional exhaustion (EE) (F = 26.528, P < 0.01). Factors that significantly predicted depersonalization (DP) included male gender, senior residents, night shift experience, high occupational stress, and low psychological empathy, which explained 51.5% variance totally (F = 29.004, P < 0.01). Senior residents, high income, low occupational stress, and high empathy were also significant predictors of decreased personal achievement (PA), which explained 18.4% variance totally (F = 12.897, P < 0.01). CONCLUSIONS: There was a high burnout rate among SRT residents in Shanghai. Occupational stress and several work-related factors were significant and strong risk factors for burnout, while empathy and social support were mild protective factors. Decreased work-related demands and increased access to resources could assist residents in reducing their work stress and improving their well-being.