Clinical characteristics of extracorporeal cardiopulmonary resuscitation in China: a multicenter retrospective study.

PURPOSE: Extracorporeal cardiopulmonary resuscitation (ECPR) might markedly increase the survival of selected patients with refractory cardiac arrest. But the application situation and indications remained unclear. MATERIALS AND METHODS: We respectively reviwed all adult patients who underwent ECPR from January 2017 to March 2021. Patient characteristics, initiation and management of ECMO, complications, and outcomes were collected and compared between the survivors and nonsurvivors. LASSO regression was used to screen risk factors. Multivariate logistic regression was performed with several parameters screened by LASSO regression. RESULTS: Data were reported from 42 ECMO centers covering 19 provinces of China. A total of 648 patients were included in the study, including 491 (75.8%) males. There were 11 ECPR centers in 2017, and the number increased to 42 in 2020. The number of patients received ECPR increased from 33 in 2017 to 274 in 2020, and the survival rate increased from 24.2% to 33.6%. Neurological complications, renal replacement therapy, epinephrine dosage after ECMO, recovery of spontaneous circulation before ECMO, lactate clearance and shockable rhythm were risk factors independently associated with outcomes of whole process. Sex, recovery of spontaneous circulation before ECMO, lactate, shockable rhythm and causes of arrest were pre-ECMO risk factors independently affecting outcomes. CONCLUSIONS: From January 2017 to March 2021, the numbers of ECPR centers and cases in mainland China increased gradually over time, as well as the survival rate. Pre-ECMO risk factors, especially recovery of spontaneous circulation before ECMO, shockable rhythm and lactate, are as important as post-ECMO management,. Neurological complications are vital risk factors after ECMO that deserved close attention. TRIAL REGISTRATION: NCT04158479, registered on 2019/11/08. https://clinicaltrials.gov/NCT04158479.

Identification of VEGFs-related gene signature for predicting microangiogenesis and hepatocellular carcinoma prognosis.

Microangiogenesis is an important prognostic factor in various cancers, including hepatocellular carcinoma (HCC). The Vascular Endothelial Growth Factor (VEGF) has been shown to contribute to tumor angiogenesis. Recently, several studies have investigated the regulation of VEGF production by a single gene, with few researchers exploring all genes that affect VEGF production. In this study, we comprehensively analyzed all genes affecting VEGF production in HCC and developed a risk model and gene-based risk score based on VEGF production. Moreover, the model's predictive capacity on prognosis of HCCs was verified using training and validation datasets. The developed model showed good prediction of the overall survival rate. Patients with a higher risk score experienced poor outcomes compared to those with a lower risk score. Furthermore, we identified the immunological causes of the poor prognosis of patients with high-risk scores comparing with those with low-risk scores.

Severe Pain and Postoperative Effects during Hysterosalpingography: A Meta-Analysis.

Background: We aimed to evaluate the impact of pain on patients during Hysterosalpingography (HSG). Methods: PubMed, PMC and other journals were searched for randomized controlled trials (RCTS) on HSG. Appropriate articles were selected for inclusion and reasonable exclusion according to keywords. Following a thorough review of the relevant literature, the process of literature screening was conducted in accordance with the aforementioned criteria. The methodological quality of the studies was assessed using the risk of bias assessment tool developed by the Cochrane Collaboration. Meta-analysis was conducted using RevMan 5.4.1 software. Results: Twelve studies were included, including 1530 cases in the experimental group and 1545 cases in the control group. The literature summarizes the basic information of patients during HSG and makes statistics on the differences in visual analog scale (VAS) and pain perception. The findings from the HSG examination revealed a lack of significant association between patients' pain sensation and their age and BMI. However, the duration of pregnancy in patients decreased following HSG treatment (95%CI (-18.84 to -3.58), P=0.004).Compared with conventional testing, HSG could effectively reduce the pregnancy time of patients (95%CI (-18.84, -3.58), P=0.004), reduce the VAS of patients (95%CI (-4.73, -1.51), P=0.0001), and increase the number of patients without pain (95%CI (1.80, 10.43), P=0.001). Conclusion: During the HSG examination, acceptable pain avoidance is generated and can be relieved over time. At present, there is no effective alternative method, so the patient should cooperate with the doctor to complete the examination, to relieve the pain.

Conditional deletion of Zeb1 in Csf1r+ cells reduces inflammatory response of the cornea to alkali burn.

ZEB1 is an essential factor in embryonic development. In adults, it is often highly expressed in malignant tumors with low expression in normal tissues. The major biological function of ZEB1 in developing embryos and progressing cancers is to transdifferentiate cells from an epithelial to mesenchymal phenotype; but what roles ZEB1 plays in normal adult tissues are largely unknown. We previously reported that the reduction of Zeb1 in monoallelic global knockout (Zeb1+/-) mice reduced corneal inflammation-associated neovascularization following alkali burn. To uncover the cellular mechanism underlying the Zeb1 regulation of corneal inflammation, we functionally deleted Zeb1 alleles in Csf1r+ myeloid cells using a conditional knockout (cKO) strategy and found that Zeb1 cKO reduced leukocytes in the cornea after alkali burn. The reduction of immune cells was due to their increased apoptotic rate and linked to a Zeb1-downregulated apoptotic pathway. We conclude that Zeb1 facilitates corneal inflammatory response by maintaining Csf1r+ cell viability.

Esmolol increases the fecal abundance of Lactobacillus in a rat model of sepsis.

BACKGROUND: Disorders of the gut microbiome could be responsible for the progression of multiple organ dysfunction syndrome. In this study, we examined the effect of esmolol on the gut microbiome in a rat model of sepsis induced by cecal ligation and puncture (CLP). METHODS: The animals (n = 32) were randomly divided into 3 groups: Sham group (sham operation + normal saline treatment, n = 8), CLP group (cecal ligation and puncture + normal saline treatment, n = 12), and CLP + ESM group (cecal ligation and puncture + esmolol treatment, n = 12). After 24 h, feces in the colon were collected for 16S rRNA gene sequencing and nitric oxide analysis. In addition, colon was removed for immunohistochemical staining of inducible nitric oxide synthase (iNOS). RESULTS: Four rats in the CLP group and two rats in the CLP + ESM group died. The abundance of Lactobacillus in the CLP + ESM group was higher than CLP group (P = 0.048). In the linear discriminant analysis effect size analysis, Norank f Muribaculaceae, Escherichia-Shigella and Lactobacillus were the predominant bacteria in the Sham group, CLP group and CLP + ESM group, respectively. The iNOS expression in colonocytes stained by brown in the CLP group were much more than Sham group (P = 0.001). Compared to CLP group, the iNOS expression in colonocytes reduced after esmolol treatment (P = 0.013). The concentration of nitric oxide in colon feces was different in Sham group, CLP group and CLP + ESM group (1.31 ± 0.15µmmol/l vs. 1.98 ± 0.27µmmol/l vs. 1.51 ± 0.14µmmol/l, P = 0.001). In addition, the concentration of nitric oxide in CLP group was higher than Sham group (P = 0.001) or CLP + ESM group (P = 0.001). CONCLUSIONS: Esmolol increased the fecal abundance of Lactobacillus in a rat model of sepsis. Moreover, esmolol reduced the iNOS expression of colonocytes and the nitric oxide concentration of colon feces.

Nasal Endoscopic Incision and Drainage Transnasal Retropterygoid Approach to Upper Parapharyngeal Abscess: A Novel Technique.

Parapharyngeal infection is a well-known disease of otorhinolaryngologists. Rapid onset, short duration, severe symptoms, and manifestations such as sore throat and dysphagia are common characteristics treated primarily by surgical incision and drainage. Traditional surgical approaches encompass endoscopic transoral/nasal, transparotid, transcervical, or a combination thereof. We report a novel technique of nasal endoscopic incision and drainage transnasal retropterygoid approach to an upper parapharyngeal abscess. This report presents a case of a 14-year-old man presented with severe right neck and head pain, who was found to have an upper parapharyngeal abscess during a nasal endoscopic parapharyngeal exploration via a retropterygoid approach. The intraoperative frozen section revealed chronic mucosal inflammation and mild to moderate dysplasia of the squamous epithelium, but no carcinoma.

Artificial intelligence techniques for ground fault line selection in power systems: State-of-the-art and research challenges.

In modern power systems, efficient ground fault line selection is crucial for maintaining stability and reliability within distribution networks, especially given the increasing demand for energy and integration of renewable energy sources. This systematic review aims to examine various artificial intelligence (AI) techniques employed in ground fault line selection, encompassing artificial neural networks, support vector machines, decision trees, fuzzy logic, genetic algorithms, and other emerging methods. This review separately discusses the application, strengths, limitations, and successful case studies of each technique, providing valuable insights for researchers and professionals in the field. Furthermore, this review investigates challenges faced by current AI approaches, such as data collection, algorithm performance, and real-time requirements. Lastly, the review highlights future trends and potential avenues for further research in the field, focusing on the promising potential of deep learning, big data analytics, and edge computing to further improve ground fault line selection in distribution networks, ultimately enhancing their overall efficiency, resilience, and adaptability to evolving demands.

Temporal transcriptome features identify early skeletal commitment during human epiphysis development at single-cell resolution.

Human epiphyseal development has been mainly investigated through radiological and histological approaches, uncovering few details of cellular temporal genetic alternations. Using single-cell RNA sequencing, we investigated the dynamic transcriptome changes during post-conception weeks (PCWs) 15-25 of human distal femoral epiphysis cells. We find epiphyseal cells contain multiple subtypes distinguished by specific markers, gene signatures, Gene Ontology (GO) enrichment analysis, and gene set variation analysis (GSVA). We identify the populations committed to cartilage or ossification at this time, although the secondary ossification centers (SOCs) have not formed. We describe the temporal alternation in transcriptional expression utilizing trajectories, transcriptional regulatory networks, and intercellular communication analyses. Moreover, we find the emergence of the ossification-committed population is correlated with the COL2A1-(ITGA2/11+ITGB1) signaling. NOTCH signaling may contribute to the formation of cartilage canals and ossification via NOTCH signaling. Our findings will advance the understanding of single-cell genetic changes underlying fetal epiphysis development.

Decellularized Porcine Conjunctiva in Treating Severe Symblepharon.

This prospective study aimed to evaluate the effectiveness of decellularized porcine conjunctiva (DPC) in the management of severe symblepharon. Sixteen patients with severe symblepharon were enrolled in this study. After symblepharon lysis and Mitomycin C (MMC) application, tarsus defects were covered with residual autologous conjunctiva (AC), autologous oral mucosa (AOM), or DPC throughout the fornix, and DPC was used for all the exposed sclera. The outcomes were classified as complete success, partial success, or failure. Six symblepharon patients had chemical burns and ten had thermal burns. Tarsus defects were covered with DPC, AC, and AOM in two, three, and eleven cases, respectively. After an average follow-up of 20.0 ± 6 months, the anatomical outcomes observed were complete successes in twelve (three with AC+DPC, four with AC+AOM+DPC, and five with AOM+DPC) (75%) cases, partial successes in three (one with AOM+DPC and two with DPC+DPC) (18.75%) cases, and failure in one (with AOM+DPC) (6.25%) case. Before surgery, the depth of the narrowest part of the conjunctival sac was 0.59 ± 0.76 mm (range, 0-2 mm), tear fluid quantity (Schirmer II tests) was 12.5 ± 2.26 mm (range, 10-16 mm), and the distance of the eye rotation toward the opposite direction of the symblepharon was 3.75 ± 1.39 mm (range, 2-7 mm). The fornix depths increased to 7.53 ± 1.64 mm (range, 3-9 mm), eye movement was significantly improved, and the distance of eye movement reaching 6.56 ± 1.24 mm (range, 4-8 mm) 1 month after the operation; the postoperative Schirmer II test (12.06 ± 2.90 mm, range, 6-17 mm) was similar to that before surgery. Goblet cells were finally found in fifteen patients by conjunctival impression cytology in the transplantation area of DPC, except for one patient who failed. DPC could be considered an alternative for ocular surface reconstruction of severe symblepharon. Covering tarsal defects with autologous mucosa is necessary for extensive reconstruction of the ocular surface.

hsa_circ_0051428 Facilitates the Progression of Thyroid Cancer by Sponging miR-1248 to Up-Regulate FN1.

Evidence displays that circular RNAs (circRNAs) are considerable mediators of numerous processes in cancer development. Given that many circRNAs are not functionally characterized, our aim was to explore the function and mechanisms of circ_0051428 in thyroid cancer (TC). The analysis of circ_0051428, miR-1248 and FN1 mRNA expression was conducted using real-time quantitative polymerase chain reaction. Cell growth was observed using CCK-8 and colony formation assays. Cell migration was investigated using wound healing assay. Cell apoptosis was identified by the expression of apoptosis-related proteins (Bax and Bcl-2) using Western blotting. Animal models were established to testify the role of circ_0051428 in vivo. The assumed binding between miR-1248 and circ_0051428 or FN1 was identified using dual-luciferase reporter or RIP assay. circ_0051428 exhibits an abnormally elevated expression in TC. circ_0051428 deficiency caused inhibition of TC cell proliferation, migration, clonogenic capacity, and inhibition of tumor growth in vivo. circ_0051428 directly targeted miR-1248, and FN1 was a target downstream of circ_0051428/miR-1248 axis. circ_0051428 could sponge miR-1248 to upregulate FN1. Furthermore, miR-1248 downregulation recovered circ_0051428 deficiency-suppressed cancer cell proliferation, survival and migration. Besides, the repressive effects of FN1 knockdown on cancer cell growth, survival and migration were also partly abolished by miR-1248 downregulation. circ_0051428 targeted miR-1248 to modulate FN1 expression, thereby facilitating the malignant progression of TC, which contributed to the understanding of the molecular mechanism of TC development.

Zeb1 facilitates corneal epithelial wound healing by maintaining corneal epithelial cell viability and mobility.

The cornea is the outmost ocular tissue and plays an important role in protecting the eye from environmental insults. Corneal epithelial wounding provokes pain and fear and contributes to the most ocular trauma emergency assessments worldwide. ZEB1 is an essential transcription factor in development; but its roles in adult tissues are not clear. We identify Zeb1 is an intrinsic factor that facilitates corneal epithelial wound healing. In this study, we demonstrate that monoallelic deletion of Zeb1 significantly expedites corneal cell death and inhibits corneal epithelial EMT-related cell migration upon an epithelial debridement. We provide evidence that Zeb1-regulation of corneal epithelial wound healing is through the repression of genes required for Tnfa-induced epithelial cell death and the induction of genes beneficial for epithelial cell migration. We suggest utilizing TNF-α antagonists would reduce TNF/TNFR1-induced cell death in the corneal epithelium and inflammation in the corneal stroma to help corneal wound healing.

Cholinergic regulation of vascular endothelial function by human ChAT+ T cells.

Endothelial dysfunction and impaired vasodilation are linked with adverse cardiovascular events. T lymphocytes expressing choline acetyltransferase (ChAT), the enzyme catalyzing biosynthesis of the vasorelaxant acetylcholine (ACh), regulate vasodilation and are integral to the cholinergic antiinflammatory pathway in an inflammatory reflex in mice. Here, we found that human T cell ChAT mRNA expression was induced by T cell activation involving the PI3K signaling cascade. Mechanistically, we identified that ChAT mRNA expression was induced following the attenuation of RE-1 Silencing Transcription factor REST-mediated methylation of the ChAT promoter, and that ChAT mRNA expression levels were up-regulated by GATA3 in human T cells. In functional experiments, T cell-derived ACh increased endothelial nitric oxide-synthase activity, promoted vasorelaxation, and reduced vascular endothelial activation and promoted barrier integrity by a cholinergic mechanism. Further, we observed that survival in a cohort of patients with severe circulatory failure correlated with their relative frequency of ChAT +CD4+ T cells in blood. These findings on ChAT+ human T cells provide a mechanism for cholinergic immune regulation of vascular endothelial function in human inflammation.

Mechanism analysis of hydroxypropyl guar gum degradation in fracture flowback fluid by homogeneous sono-Fenton process.

An effective hybrid system was applied as the first report for the successful treatment of key pollutants (hydroxypropyl guar gum, HPG) in fracturing flowback fluid, and the synergistic index of the hybrid system was 20.45. In this regard, chemical oxygen demand (COD) removal ratio was evaluated with various influencing operating factors including reaction time, H2O2 concentration, Fe2+ concentration, ultrasonic power, initial pH, and temperature. The optimal operating parameters by single-factor analysis method were: the pH of 3.0, the H2O2 concentration of 80 mM, the Fe2+ concentration of 5 mM, the ultrasonic power of 180 W, the ultrasonic frequency of 20-25 kHz, the temperature of 39 â„ƒ, the reaction time of 30 min, and the COD removal rate reached 81.15 %, which was permissible to discharge surface water sources based on the environmental standards. A possible mechanism for HPG degradation and the generation of reactive species was proposed. Results of quenching tests showed that various impacts of the decomposition rate by addition of scavengers had followed the order of EDTA-2Na < BQ < t-BuOH, therefore OH radicals had a dominant role in destructing the HPG. Based on the kinetic study, it was concluded that Chan Kinetic Model was more appropriate to describe the degradation of HPG. Identification of intermediates by GC-MS showed that a wide range of recalcitrant compounds was removed and/or degraded into small molecular compounds effectively after treatment. Under the optimal conditions, the sono-Fenton system was used to treat the fracturing flowback fluid with the initial COD value of 675.21 mg/L, and the COD value decreased to 80.83 mg/L after 60 min treatment, which was in line with the marine sewage discharge standard. In conclusion, sono-Fenton system can be introduced as a successful advanced treatment process for the efficient remediation of fracture flowback fluid.

CircSMAD2 accelerates endometrial cancer cell proliferation and metastasis by regulating the miR-1277-5p/MFGE8 axis.

OBJECTIVE: Endometrial cancer (EC) is a common gynecological malignant tumor. CircRNAs play crucial roles in cancer progression and metastasis. However, the biological functions of circRNAs in EC remain largely unknown. METHODS: CircSMAD2, miR-1277-5p, MFGE8 and relative maker protein expression in EC tissues or cell lines were analyzed by quantitative real-time polymerase chain reaction and Western blot. In vitro and in vivo functional assays, including EDU, CCK8, colony formation, transwell, tube formation and tumor xenograft assays, were conduct to explore the effects of circSMAD2 on EC. Mechanism assays were conducted to confirm the binding between miR-1277-5p and circSMAD2 or MFGE8 expression. RESULTS: Upregulation of circSMAD2 was uncovered in both EC tissues and cell lines. Functionally, silencing of circSMAD2 apparently inhibited the proliferation, migration, invasion and angiogenesis of EC cell lines in vitro. Mechanistically, circSMAD2 sponged miR-1277-5p to upregulate MFGE8 expression. The decrease of miR-1277-5p and increase of MFGE8 were observed both in EC tissues and cell lines. Then MFGE8 knockdown or miR-1277-5p upregulation suppressed EC cell oncogenic biological behavior. Rescue experiments showed that miR-1277-5p mimics countervailed the anticancer effects of circSMAD2 silencing on EC. Besides that, MFGE8 overexpression also attenuated the inhibitory action of miR-1277-5p mimic in EC. Moreover, knockdown of circSMAD2 inhibited EC growth in vivo. CONCLUSION: CircSMAD2 functions as an oncogene in promoting the progression of EC through miR-1277-5p/MFGE8 axis.

Isolation and Characterization of Lactobacillus paracasei 85 and Lactobacillus buchneri 93 to Absorb and Biotransform Zearalenone.

As one of the most prevalent estrogenic mycotoxins in cereals and animal feed, zearalenone (ZEN) can cause serious reproductive disorders. ZEN control in food and feed commodities has been an imperative area of research. In this study, 87 lactic acid bacteria (LAB) were isolated from pickles and their ZEN (5 mg/L) removal abilities ranged from 0% to 68.4%. Then, five strains with potent ZEN removal ability (>50%) were identified: Lactobacillus plantarum 22, L. plantarum 37, L. plantarum 47, L. paracasei 85, and L. buchneri 93. Under optimization conditions (48 h, pH 4.0, 37 °C, and 5 mg/L), the highest ZEN removal abilities of L. paracasei 85 and L. buchneri 93 reached 77.7% and 72.8%, respectively. Moreover, the two lactic acid bacteria decreased the toxicity of ZEN, because the levels of ß-zearalenol (ß-ZOL) transformed from ZEN were more than two-fold higher than α-zearalenol (α-ZOL). Additionally, cell free supernatant and pellet biotransformation of ZEN to α-ZOL and ß-ZOL in LAB were detected for the first time. Furthermore, chemical and enzymatical treatments combined with Fourier-transform infrared spectroscopy analysis indicated that exopolysaccharides, proteins, and lipids on the cell wall could bond to ZEN through hydrophobic interactions. Scanning electron microscopy indicated that cell structure damage occurred during the ZEN clearance to L. buchneri 93, but it did not with L. paracasei 85. In addition, various organic acids, alcohols, and esters of the two LAB participated in ZEN removal. Hence, L. paracasei 85 and L. buchneri 93 can be considered as potential detoxification agents for ZEN removal for food and feedstuff.

[Exploration and practice of building tele-critical care system].

OBJECTIVE: To look for the problems faced in the construction of the tele-critical care system, explore the framework of construction of the tele-critical care system, and verify the application effects of the established tele-critical care system. METHODS: Through literature review and on-site investigation and demonstration, the causes affecting the construction of the tele-critical care system were explored. Through on-site investigation of the actual situation of the critical care department in relevant hospitals, arguing and choosing intended intensive care unit (ICU) and cooperative third-party communication and equipment companies, and through the Internet of Things and 5G communication technology, a tele-critical care system with the core hospital of the group as the center and the member institutes within the group as the nodes was built. Via the established tele-critical care system, activities such as tele-monitoring, visual remote ward rounds, remote consultation, remote teaching were carried out to verify the functions of the system. RESULTS: The insufficient cognition of relevant personnel, tele-medicine practice certification requirements, information security issues and the barriers of equipment information integration were the main causes affecting the construction of tele-critical care system. There were five parts in the tele-critical care system architecture foundations, including bed unit equipment and audio and video information collection system, lossless and secure transmission of collected information, real-time display of information in the remote center, real-time staff interaction between the centre and the nodal hospitals, and information cloud storage. It has been verified that patients' diagnostic and treatment information can be transmitted safely, losslessly and in real-time by a special line through private 5G network. Through this system, real-time and stable upload of audio and video information of patients and application information of monitors, ventilators and infusion work stations can be achieved; combined with tele-conference connections to conduct two-way communication with local medical staff, real-time tele-monitoring, visual remote ward rounds, remote consultation, remote teaching and other functions can be achieved. CONCLUSIONS: The tele-critical care system we established is feasible to construct within the medical group and can safely and effectively realize the functions of real-time tele-monitoring, visual remote ward rounds, remote consultation, and remote teaching.

Study on Absorption, Distribution, Metabolism, and Excretion Properties of Novel Insecticidal GABA Receptor Antagonist, Pyraquinil, in Diamondback Moth Combining MALDI Mass Spectrometry Imaging and High-Resolution Mass Spectrometry.

A thorough understanding of absorption, distribution, metabolism, and excretion (ADME) of insecticide candidates is essential in insecticide development and structural optimization. Here, ADME of pyraquinil, a novel insecticidal GABA receptor antagonist, in Plutella xylostella larvae during the accumulation phase and depuration phase was investigated separately using a combination of UHPLC-Q-Orbitrap, HPLC-MS/MS, and MALDI-MSI. Five new metabolites of pyraquinil were identified, and a metabolic pathway was proposed. The oxidative metabolite (pyraquinil-sulfone) was identified as the main metabolite and confirmed by its standard. Quantitative results showed that pyraquinil was taken up by the larvae rapidly and then undergone a cytochrome P450s-mediated oxidative transformation into pyraquinil-sulfone. Both fecal excretion and oxidative metabolism were demonstrated to be predominant ways to eliminate pyraquinil in P. xylostella larvae during accumulation, while oxidative metabolism followed by fecal excretion was probably the major pathway during depuration. MALDI-MSI revealed that pyraquinil was homogeneously distributed in the larvae, while pyraquinil-sulfone presented a continuous enrichment in the midgut during accumulation. Conversely, pyraquinil-sulfone located in hemolymph can be preferentially eliminated during depuration, suggesting its tissue tropism. It improves the understanding of the fate of pyraquinil in P. xylostella and provides useful information for insecticidal mechanism elucidation and structural optimization of pyraquinil.

Leaf Mutant 7 Encoding Heat Shock Protein OsHSP40 Regulates Leaf Size in Rice.

Leaf size is an important agronomic trait directly affecting yield in rice, and thus understanding the genes determining leaf size is important in breeding. In this study, one Leaf Mutant 7 (lm7) with small leaf size was isolated using ethyl methane sulphonate (EMS) mutagenesis from the japonica Zhenggeng 1925. MutMap by whole genome resequencing of phenotypic bulks revealed that LM7 is likely located in the 133 kb region on chromosome 7 using F2 population from a cross between lm7 and wild-type (WT) Zhenggeng 1925. The candidate gene encoding heat shock protein OsHSP40 for LM7 was functionally validated. Disruption of this gene in Oshsp40 mutants significantly reduced the leaf size compared with that of WT in rice. Microscopic examination showed that OsHSP40 modulated leaf size via regulating the veins formation and cell size/cell number. Nucleotide diversity analysis indicated that a single nucleotide polymorphism (SNP) variation of C to T in the coding region of OsHSP40 may cause small leaves among rice accessions. Therefore, the natural variation of OsHSP40 contributing to leaf size might be useful for rice breeding.

FOXP4 differentially controls cold-induced beige adipocyte differentiation and thermogenesis.

Beige adipocytes have a discrete developmental origin and possess notable plasticity in their thermogenic capacity in response to various environmental cues, but the transcriptional machinery controlling beige adipocyte development and thermogenesis remains largely unknown. By analyzing beige adipocyte-specific knockout mice, we identified a transcription factor, forkhead box P4 (FOXP4), that differentially governs beige adipocyte differentiation and activation. Depletion of Foxp4 in progenitor cells impaired beige cell early differentiation. However, we observed that ablation of Foxp4 in differentiated adipocytes profoundly potentiated their thermogenesis capacity upon cold exposure. Of note, the outcome of Foxp4 deficiency on UCP1-mediated thermogenesis was confined to beige adipocytes, rather than to brown adipocytes. Taken together, we suggest that FOXP4 primes beige adipocyte early differentiation, but attenuates their activation by potent transcriptional repression of the thermogenic program.