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Water use efficiency (WUE) is a key indicator to assess ecosystem adaptation to water stress. Rain use efficiency (RUE) is usually used as a proxy for WUE due to lack of transpiration data. Furthermore, RUE based on aboveground primary productivity (RUEANPP) is used to evaluate whole plant water use because root production data is often missing as well. However, it is controversial as to whether RUE is a reliable parameter to elucidate transpiration efficiency (TE), and whether RUEANPP is a suitable proxy for RUE of the whole plant basis. The experiment was conducted at three differently managed sites in the Inner Mongolia steppe: a site fenced since 1979 (UG79), a winter grazing site (WG) and a heavily grazed site (HG). Site HG had consistent lowest RUEANPP and RUE based on total net primary productivity (RUENPP). RUEANPP is a relatively good proxy at sites UG79 and WG, but less reliable for site HG. Similarly, RUEANPP is good predictor of transpiration efficiency based on aboveground net primary productivity (TEANPP) at sites UG79 and WG but not for site HG. However, if total net primary productivity is considered, RUENPP is good predictor of transpiration efficiency based on total net primary productivity (TENPP) for all sites. Although our measurements indicate decreased plant transpiration and consequentially decreasing RUE under heavy grazing, productivity was relatively compensated for with a higher TE. This offset between RUE and TE was even enhanced under water limited conditions and more evident when belowground net primary productivity (BNNP) was included. These findings suggest that BNPP should be considered when studies fucus on WUE of more intensively used grasslands. The consideration of the whole plant perspective and "real" WUE would partially revise our picture of system performance and therefore might affect the discussion on the C-sequestration and resilience potential of ecosystems.

Abstract Knockout of GAS2 (growth arrest-specific protein 2), causes disorganization and destabilization of microtubule bundles in supporting cells of the cochlear duct, leading to hearing loss in vivo. However, the molecular mechanism through which GAS2 variant results in hearing loss remains unknown. By Whole-exome sequencing, we identified a novel heterozygous splicing variant in GAS2 (c.616–2 A > G) as the only candidate mutation segregating with late-onset and progressive nonsyndromic hearing loss (NSHL) in a large dominant family. This splicing mutation causes an intron retention and produces a C-terminal truncated protein (named GAS2mu). Mechanistically, the degradation of GAS2mu via the ubiquitin-proteasome pathway is enhanced, and cells expressing GAS2mu exhibit disorganized microtubule bundles. Additionally, GAS2mu further promotes apoptosis by increasing the Bcl-xS/Bcl-xL ratio instead of through the p53-dependent pathway as wild-type GAS2 does, indicating that GAS2mu acts as a toxic molecule to exacerbate apoptosis. Our findings demonstrate that this novel variant of GAS2 promotes its own protein degradation, microtubule disorganization and cellular apoptosis, leading to hearing loss in carriers. This study expands the spectrum of GAS2 variants and elucidates the underlying pathogenic mechanisms, providing a foundation for future investigations of new therapeutic strategies to prevent GAS2-associated progressive hearing loss.

ObjectiveTo provide a basis for human enteroviruses prevention and control by monitoring the enterovirus （EV） and its main virus types.MethodsSamples of hand-foot-and-mouth disease， herpetic angina and fever clinic patients in Dapeng New District of Shenzhen from 2016 to 2022 were tested for EV with real-time polymerase chain reaction （PCR）. To identify the isolates of EV， VP1 genes of EV were amplified with nested reverse transcription PCR， and then sequenced.A geneticphylogenetic tree was constructed based on the VP1 gene.ResultsAmong the 1 124 suspected hand-foot-and-mouth disease cases， 740 （65.84%） tested EV positive. Coxsackievirus A6 （CVA6） and Coxsackievirus A16 （CVA16） were the main two serotypes with regular cycle trends. Of the 137 suspected herpetic angina cases， 88 （64.23%） were EV positive， with Coxsackievirus A4 （CVA4） and CVA16 as the dominant serotypes. Among 428 respiratory infection specimens， 71 （16.59%） were EV positive. Coxsackievirus A4 （CVA4） was the predominant serotype which caused herpetic angina and respiratory infection. The epidemic EV isolates CVA6 from Shenzhen had a close genetic relationship with isolates in China’s mainland.ConclusionThe main serotypes EV CVA6 and CVA16 which caused hand-foot-and-mouth disease exhibit cyclical trends . The risk of EV transmitted from abroad is low， but their genetic variation and virulence change should be monitored continuously. In addition， the monitoring of dominant isolates CVA4 which cause herpetic angina and respiratory infection should be strengthened.

Abstract One crucial component of ghost imaging (GI) is the encoded mask. Higher-quality reconstruction at lower sampling rates is still a major challenge for GI. Inspired by deep learning, max-projection method is proposed in the paper to reorder the Hadamard masks for its efficient and rapid reconstruction. The simulations demonstrated that max-projection ordering with only 20 face training images yielded excellent reconstruction outcomes. In noise-free simulations, at an ultralow sampling rate of 5%, the PSNR of the max-projection ordering was 1.1 dB higher than that of the cake-cutting ordering with the best performance in the reference group. In noisy simulations, at ultralow sampling rates, the retrieved images remained almost identical to their noise-free counterparts. Irrespective of the presence or absence of noise, the max-projection ordering guaranteed the highest fidelity of image reconstruction at ultralow sampling rates. The reconstruction time was reduced to mere milliseconds, thereby enabling swift visualization of dynamic phenomena. Accordingly, the max-projection ordering Hadamard matrix offers a promising solution for real-time GI due to its higher reconstruction quality, stronger noise immunity and millisecond reconstruction time.

Abstract. Endometriosis, a heterogeneous, inflammatory, and estrogen-dependent gynecological disease defined by the presence and growth of endometrial tissues outside the lining of the uterus, affects approximately 5-10% of reproductive-age women, causing chronic pelvic pain and reduced fertility. Although the etiology of endometriosis is still elusive, emerging evidence supports the idea that immune dysregulation can promote the survival and growth of retrograde endometrial debris. Peritoneal macrophages and natural killer (NK) cells exhibit deficient cytotoxicity in the endometriotic microenvironment, leading to inefficient eradication of refluxed endometrial fragments. In addition, the imbalance of T-cell subtypes results in aberrant cytokine production and chronic inflammation, which contribute to endometriosis development. Although it remains uncertain whether immune dysregulation represents an initial cause or merely a secondary enhancer of endometriosis, therapies targeting altered immune pathways exhibit satisfactory effects in preventing disease onset and progression. Here, we summarize the phenotypic and functional alterations of immune cells in the endometriotic microenvironment, focusing on their interactions with microbiota and endocrine and nervous systems, and how these interactions contribute to the etiology and symptomology of endometriosis.

Squirrels of temperate zones commonly store nuts or seeds under leaf litter, in hollow logs, or even in holes in the ground; however, in the humid rainforests of Jianfengling in Hainan, South China, we show that some flying squirrels cache elliptical or oblate nuts by hanging them securely in vegetation. These small flying squirrels were identified as Hylopetes phayrei electilis (G. M. Allen, 1925) and Hylopetes alboniger (Hodgson, 1870), in video clips captured of their behavior around focal nuts. Squirrels chewed grooves encircling ellipsoid nuts or distributed on the bottoms of oblate nuts, and then used these grooves to fix nuts tightly between small twigs 0.1–0.6 cm in diameter that were connected at angles of 25–40°. The grooves carved on the nuts (concave structure) connected with Y-shaped twigs (convex structure) and thus firmly affixed the nuts to the plant in a way similar to a mortise-tenon joint used in architecture and carpentry. Cache sites were on small plants located 10–25 m away from the closest potentially nut-producing tree, a behavior that likely reduces the discovery and consumption of the nuts by other animals. The adaptive squirrel behavior that shapes and fits nuts between twigs seems to be directed at providing more secure storage that increases food supply during dry periods in a humid tropical rainforest. In addition to providing such benefits for the squirrels, we suggest that this behavior also impacts the distribution of tree species in the forest.

ObjectiveTo determine the pathogenic characteristics and genotype of two outbreaks of herpangina in children in Dapeng New District， Shenzhen， in May 2021.MethodsA total of five throat swabs from children in the two outbreaks of herpangina were collected and examined for common enteroviruses by real-time PCR. The VP1 region was further amplified by nested RT-PCR. The CLUSTAL W program in MEGA7 software was used to conduct the alignment and reconstruct a phylogenetic tree.ResultsThe pathogen causing the 2 cluster outbreaks of herpangina was coxsackievirus A4 （CVA4）. The sequences of CVA4 VP1 genes revealed that a nucleotide identity of 92% between the strains in the two outbreaks. The three CVA4 strains isolated in kindergarten A had the closest phylogenetic relationship with that isolated in Shenzhen in 2018（MN840533）， with the nucleotide identity of 98.11%. The two strains in kindergarten B had the closest phylogenetic relationship with CVA4 strain isolated in Sichuan in 2018（MW178763）， with the nucleotide identity of 97.88%. The phylogenetic tree showed that all five CVA4 strains in this study belonged to the C2 genotype.ConclusionThe C2 genotype of CVA4 is the causative agent in both outbreaks of herpangina.

Since the outbreak of coronavirus disease 2019 (COVID-19), a number of COVID-19 related thyroid disorders have been reported, including subacute thyroiditis, autoimmune thyroid disease, non-thyroidal illness syndrome and some unexplained thyroid dysfunction. This review aimed to summarize clinical characteristics of COVID-19 related thyroid disorders and to discuss some possible mechanisms.

Objective To summarize the clinical experience of intensity-modulated radiotherapy(IMRT) for patients with giant pituitary adenoma, and to provide evidence for clinical treatment. Methods The data of patients with giant pituitary adenoma who received 6MV-X IMRT with linear accelerator (prescription dose of 56-60 Gy/28-30 fractions, 5 fractions per week) in the Department of Radiation Oncology of Peking Union Medical College Hospital from October 2012 to October 2018 were reviewed. Treatment outcomes were evaluated by the control rate of tumor growth, remission rate of endocrine hormone, and radiation-related complications. Results A total of 15 patients were included in this study. There were 8 males and 7 females with a median age of 32 years. The control rate of tumor growth was 93.3% (partial response in 11 cases, stable in 3 cases, and development of pituitary carcinoma in 1 case). Among the 7 patients with functional giant pituitary adenoma, 1 patient achieved complete remission of the level of endocrine hormone and 2 patients achieved partial remission. Four patients treated with radiotherapy plus temozolomide achieved partial remission (median remission time was 5 months), and the remission rate and remission time were better than those who did not receive temozolomide. During the follow-up period after radiotherapy, 4 patients were found having newly pituitary dysfunction. There were no new or aggravating visional impairment and visual field defects. Conclusion Intensity-modulated radiotherapy is an effective treatment for giant pituitary adenoma, which can reduce the tumor faster combined with temozolomide.

By stimulating social vitality and improving innovation efficiency, intergenerational mobility plays an essential role in economic development. With the data from China Labor-force Dynamic Survey (CLDS) and A-share listed companies, this paper uses the methodology of intergenerational order correlation to measure regional intergenerational mobility, and examines the impact of regional intergenerational mobility on corporate innovation. The results are as follows: (1) Regional intergenerational mobility promotes corporate innovation both quantitatively and qualitatively, and a series of robustness tests confirm our findings; (2) Two channels identified are government-enterprise human capital allocation and fairness perception; (3) Heterogeneity analysis shows that the innovation effect of regional intergenerational mobility is more significant in the high-tech industry and private enterprises; (4) Multi-dimensional market-oriented policy can be used to get rid of the shackles of low intergenerational mobility on corporate innovation. Our findings provide implications for developing countries on how to address the relationship between inequality and economic development.

Bacillus thuringiensis insecticidal proteins (Bt toxins) have been widely used in crops for agricultural pest management and to reduce the use of chemical insecticides. Here, we have engineered Bt toxin Cry2Ab30 and bioconjugated it with 4”-O-succinyl avermectin (AVM) to synthesize Cry2Ab−AVM bioconjugate. It was found that Cry2Ab−AVM showed higher insecticidal activity against Plutella xylostella, up to 154.4 times compared to Cry2Ab30. The binding results showed that Cry2Ab−AVM binds to the cadherin-like binding protein fragments, the 10th and 11th cadherin repeat domains in the P. xylostella cadherin (PxCR10−11), with a much higher affinity (dissociation equilibrium constant KD = 3.44 nM) than Cry2Ab30 (KD = 28.7 nM). Molecular docking suggested that the macrolide lactone group of Cry2Ab−AVM ligand docking into the PxCR10−11 is a potential mechanism to enhance the binding affinity of Cry2Ab−AVM to PxCR10−11. These findings offer scope for the engineering of Bt toxins by bioconjugation for improved pest management.

Hepatocyte growth factor (HGF) is a paracrine hormone that plays an important role in epithelial-mesenchymal transition. HGF secreted by mesenchymal cells affects many properties of epithelial cells, such as proliferation, motility, and morphology. HGF has been reported to promote follicular growth. The purpose of the present study is to investigate the therapeutic role of HGF in hair loss treatment. A recombinant vector containing the human HGF (hHGF) gene (pTARGET-hHGF) was constructed, and the expression of hHGF in vitro was quantitatively and qualitatively evaluated. The effect of hHGF on hair growth was tested in mice, and results demonstrated that pTARGET-hHGF was successfully delivered into fibroblasts in vitro leading to a high expression of hHGF. Local injections of the pTARGET-hHGF recombinant vector into mice resulted in multiple beneficial effects compared to placebo, including faster hair regeneration, improved follicle development, and significantly increased HGF receptor (HGF-R). In conclusion, we have established a nonviral vector of hHGF which could be utilized to manipulate the sheath fibroblasts surrounding hair follicles (HF), thereby stimulating hair regeneration.

Long noncoding RNAs (lncRNAs) are pervasively transcribed and play a key role in tumorigenesis. The aim of the study was to determine the lncRNA expression profile in astrocytomas and to assess its potential clinical value. We performed a three-step analysis to establish the lncRNA profile for astrocytoma: a) the lncRNA expression was examined on 3 astrocytomas as well as 3 NATs (normal adjacent tissues) using the lncRNA microarray; b) the top-hits were validated in 40 astrocytomas (WHO grade II-IV) by quantitative real time-PCR (qRT-PCR); c) the hits with significant differences were re-evaluated using qRT-PCR in 90 astrocytomas. Finally, 7 lncRNAs were found to have a significantly different expression profile in astrocytoma samples compared to the NAT samples. Unsupervised clustering analysis further revealed the potential of the 7-lncRNA profile to differentiate between tumors and NAT samples. The upregulation of ENST00000545440 and NR_002809 was associated with advanced clinical stages of astrocytoma. Using Kaplan-Meier survival analysis, we showed that the low expression of BC002811 or XLOC_010967, or the high expression of NR_002809 was significantly associated with poor patient survival. Moreover, Cox proportional hazard regression analysis revealed that this prognostic impact was independent of other clinicopathological factors. Our results indicate that the lncRNA profile may be a potential prognostic biomarker for the prediction of post-surgical outcomes.

MicroRNAs (miRNAs) are small, short noncoding RNAs that modulate the expression of numerous genes by targeting their mRNA. Numerous abnormal miRNA expression patterns are observed in various human malignancies, and certain miRNAs can act as oncogenes or tumor suppressors. Astrocytoma, the most common neuroepithelial cancer, represents the majority of malignant brain tumors in humans. In our previous studies, we found that the downregulation of miR-181b-5p in astrocytomas is associated with a poor prognosis. The aim of the present study was to investigate the functional role of miR-181b-5p and its possible target genes. miR-181b-5p was significantly downregulated in astrocytoma specimens, and the reduced expression of miR-181b-5p was inversely correlated with the clinical stage. The ectopic expression of miR-181b-5p inhibited proliferation, migration and invasion and induced apoptosis in astrocytoma cancer cells in vitro. The NOVA1 (neuro-oncological ventral antigen 1) gene was further identified as a novel direct target of miR-181b-5p. Specifically, miR-181b-5p bound directly to the 3'-untranslated region (UTR) of NOVA1 and suppressed its expression. In clinical specimens, NOVA1 was overexpressed, and its protein levels were inversely correlated with miR-181b-5p expression. Furthermore, the changing level of NOVA1 was significantly associated with a poor survival outcome. Similar to restoring miR-181b-5p expression, downregulating NOVA1 inhibited cell growth, migration and invasion. Overexpression of NOVA1 reversed the inhibitory effects of miR-181b-5p. Our results indicate that miR-181b-5p is a tumor suppressor in astrocytoma that inhibits tumor progression by targeting NOVA1. These findings suggest that miR-181b-5p may serve as a novel therapeutic target for astrocytoma.

Astrocytomas are common malignant intracranial tumors that comprise the majority of adult primary central nervous system tumors. MicroRNAs (miRNAs) are small, non-coding RNAs (20-24 nucleotides) that post-transcriptionally modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. In our previous studies, we found that the downregulation of miR-106a-5p in astrocytomas is associated with poor prognosis. However, its specific gene target(s) and underlying functional mechanism(s) in astrocytomas remain unclear. In this study, we used mRNA microarray experiments to measure global mRNA expression in the presence of increased or decreased miR-106a-5p levels. We then performed bioinformatics analysis based on multiple target prediction algorithms to obtain candidate target genes that were further validated by computational predictions, western blot analysis, quantitative real-time PCR, and the luciferase reporter assay. Fas-activated serine/threonine kinase (FASTK) was identified as a direct target of miR-106a-5p. In human astrocytomas, miR-106a-5p is downregulated and negatively associated with clinical staging, whereas FASTK is upregulated and positively associated with advanced clinical stages, at both the protein and mRNA levels. Furthermore, Kaplan-Meier analysis revealed that the reduced expression of miR-106a-5p or the increased expression of FASTK is significantly associated with poor survival outcome. These results further supported the finding that FASTK is a direct target gene of miR-106a-5p. Next, we explored the function of miR-106a-5p and FASTK during astrocytoma progression. Through gain-of-function and loss-of-function studies, we demonstrated that miR-106a-5p can significantly inhibit cell proliferation and migration and can promote cell apoptosis in vitro. The knockdown of FASTK induced similar effects on astrocytoma cells as those induced by the overexpression of miR-106a-5p. These observations suggest that miR-106a-5p functions as a tumor suppressor during the development of astrocytomas by targeting FASTK.

As a second messenger, Ca(2+) plays a major role in cold induced transduction via stimulus-specific increases in [Ca(2+)]cyt, which is called calcium signature. During this process, CAXs (Ca(2+)/H(+) exchangers) play critical role. For the first time, a putative Ca(2+)/H(+) exchanger GhCAX3 gene from upland cotton (Gossypium hirsutum cv. 'YZ-1') was isolated and characterized. It was highly expressed in all tissues of cotton except roots and fibers. This gene may act as a regulator in cotton's response to abiotic stresses as it could be up-regulated by Ca(2+), NaCl, ABA and cold stress. Similar to other CAXs, it was proved that GhCAX3 also had Ca(2+) transport activity and the N-terminal regulatory region (NRR) through yeast complementation assay. Over-expression of GhCAX3 in tobacco showed less sensitivity to ABA during seed germination and seedling stages, and the phenotypic difference between wild type (WT) and transgenic plants was more significant when the NRR was truncated. Furthermore, GhCAX3 conferred cold tolerance in yeast as well as in tobacco seedlings based on physiological and molecular studies. However, transgenic plant seeds showed more sensitivity to cold stress compared to WT during seed germination, especially when expressed in N-terminal truncated version. Finally, the extent of sensitivity in transgenic lines was more severe than that in WT line under sodium tungstate treatment (an ABA repressor), indicating that ABA could alleviate cold sensitivity of GhCAX3 seeds, especially in short of its NRR. Meanwhile, we also found that overexpression of GhCAX3 could enhance some cold and ABA responsive marker genes. Taken together, these results suggested that GhCAX3 plays important roles in the cross-talk of ABA and cold signal transduction, and compared to full-length of GhCAX3, the absence of NRR could enhance the tolerance or sensitivity to cold stress, depending on seedling's developmental stages.

Most cancer cells exhibit a shift in glucose metabolic strategy, displaying increased glycolysis even with adequate oxygen supply. SUMO-specific proteases (SENPs) de-SUMOylate substrates including HIF1α and p53,two key regulators in cancer glucose metabolism, to regulate their activity, stability and subcellular localization. However, the role of SENPs in tumor glucose metabolism remains unclear. Here we report that SUMO-specific protease 2 (SENP2) negatively regulates aerobic glycolysis in MCF7 and MEF cells. Over-expression of SENP2 reduces the glucose uptake and lactate production, increasing the cellular ATP levels in MCF7 cells, while SENP2 knockout MEF cells show increased glucose uptake and lactate production along with the decreased ATP levels. Consistently, the MCF7 cells over-expressing SENP2 exhibit decreased expression levels of key glycolytic enzymes and an increased rate of glucose oxidation compared with control MCF7 cells, indicating inhibited glycolysis but enhanced oxidative mitochondrial respiration. Moreover, SENP2 over-expressing MCF7 cells demonstrated a reduced amount of phosphorylated AKT, whereas SENP2 knockout MEFs exhibit increased levels of phosphorylated AKT. Furthermore, inhibiting AKT phosphorylation by LY294002 rescued the phenotype induced by SENP2 deficiency in MEFs. In conclusion, SENP2 represses glycolysis and shifts glucose metabolic strategy, in part through inhibition of AKT phosphorylation. Our study reveals a novel function of SENP2 in regulating glucose metabolism.