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Abstract Objective To summarize the clinical features and genetic mutation characteristics of Chinese children with KCNQ2‐related epilepsy. Methods A cohort of children with genetically caused epilepsy was evaluated at Linyi People's Hospital from January 2017 to December 2023. After next‐generation sequencing and pathogenicity analysis, we summarized the medical records and genetic testing data of the children who had KCNQ2 gene mutations. Results We identified 23 KCNQ2 gene mutations. 73.9% (n = 17) of the mutation sites were located in S5–S6 segments and the C‐terminal region. In addition to the common phenotypes, 2 new phenotypes were identified: infantile convulsion with paroxysmal choreoathetosis (ICCA) and febrile seizure plus (FS+). Of all the cases with abnormal video‐electro‐encephalography, three cases with self‐limited familial infantile epilepsy (SeLNE) exhibited a small number of multifocal discharges. Of the patients who have taken a particular antiepileptic drug, the statistics on the number of patients who have responded to the drug are as follows: oxcarbazepine (8/9, 88.9%), levetiracetam (5/7, 71.4%), phenobarbital (9/16, 56.3%), and topiramate (2/5, 40.0%). However, the efficacy of phenobarbital varied widely in treating SeLNE and KCNQ2‐DEE. At the final follow‐up, 1 case with SeLNE had a transient developmental regression and 7 cases with KCNQ2‐DEE had mild to severe developmental backwardness. Significance Although clinically rare, we report 10 new KCNQ2 mutations and two new phenotypes: ICCA and FS+. This further expands genetic and phenotypic spectrum of KCNQ2‐related epilepsy. The gene mutation sites are mostly located in S5–S6 segments and the C‐terminal region, and the former is usually associated with KCNQ2‐DEE. Sodium channel blockers (including oxcarbazepine and topiramate) and levetiracetam should be prioritized over phenobarbital for KCNQ2‐DEE. Some cases with KCNQ2‐related epilepsy may have transient developmental regression during periods of frequent seizures. Early treatment and early seizure control may be beneficial for willing outcomes in children with KCNQ2‐DEE. Plain Language Summary This article reports 23 cases of children with KCNQ2‐related epilepsy, including 10 new mutation sites and 2 new phenotypes. It further expands the genetic and phenotypic spectrum of KCNQ2‐related epilepsy. In addition, the article summarizes the gene mutation characteristics and clinical manifestations of children with KCNQ2‐related epilepsy, with the expectation of providing a certain theoretical basis for the diagnosis and treatment of such patients.

Abstract TGF-β1 activation of hepatic stellate cells (HSCs), transcriptional activator 3 (Stat3) activation and short chain fatty acids (SCFAs), metabolite of intestinal bacteria, is closely associated with hepatic fibrosis. Previous studies have shown that Lactucin has significant anti-inflammatory and hepatoprotective effects; however, the mechanism of Lactucin's role in liver fibrosis associated with SCFAs remains unknown. This study was intended to investigate whether effect of Lactucin on liver fibrosis was mediated by TGF-β1/Stat3 and SCFAs. We found that Lactucin induced apoptosis in HSC-T6 cells, and inhibition of nuclear translocation of Stat3 and p-Stat3. And Smad3 and TGF-β1 protein expression was significantly inhibited, while TLR4 and Smad7 protein expression was significantly enhanced. For in vivo experiments, we demonstrated that Lactucin alleviated liver fibrosis in mice, as evidenced by a reduction in inflammatory factors, collagen deposition, liver injury and fibrosis-related factors expression, especially the expression of Smad3 and TGF-β1 proteins was significantly suppressed and Smad7 protein expression was significantly increased in the liver. In addition, the levels of acetic acid, butyric acid and valeric acid in the intestine of Lactucin-treated mice were significantly higher than those in the intestine of liver fibrosis mice. In conclusion, based on the results of in vivo and in vitro experiments, preventive mechanism of Lactucin against liver fibrosis in mice may be to improve the enterohepatic circulation by regulating the metabolites of intestinal microorganisms, acetic acid and butyric acid, and to further regulate the Stat3 and TGF-β1 signaling pathway through the "gut-liver axis" to combat liver fibrosis.

Abstract Background Despite recent advances the prognosis of pulmonary hypertension remains poor and warrants novel therapeutic options. Extensive studies, including ours, have revealed that hypoxia-induced pulmonary hypertension is associated with high oxidative stress. Cerium oxide nanozyme or nanoparticles (CeNPs) have displayed catalytic activity mimicking both catalase and superoxide dismutase functions and have been widely used as an anti-oxidative stress approach. However, whether CeNPs can attenuate hypoxia-induced pulmonary vascular oxidative stress and pulmonary hypertension is unknown. Results In this study, we designed a new ceria nanozyme or nanoparticle (AuCeNPs) exhibiting enhanced enzyme activity. The AuCeNPs significantly blunted the increase of reactive oxygen species and intracellular calcium concentration while limiting proliferation of pulmonary artery smooth muscle cells and pulmonary vasoconstriction in a model of hypoxia-induced pulmonary hypertension. In addition, the inhalation of nebulized AuCeNPs, but not CeNPs, not only prevented but also blunted hypoxia-induced pulmonary hypertension in rats. The benefits of AuCeNPs were associated with limited increase of intracellular calcium concentration as well as enhancement of extracellular calcium-sensing receptor (CaSR) activity and expression in rat pulmonary artery smooth muscle cells. Nebulised AuCeNPs showed a favorable safety profile, systemic arterial pressure, liver and kidney function, plasma Ca2+ level, and blood biochemical parameters were not affected. Conclusion We conclude that AuCeNPs is an improved reactive oxygen species scavenger that effectively prevents and treats hypoxia-induced pulmonary hypertension. Graphical Abstract

Temperature regulating fibers (TRFs) with high enthalpy and high form stability are the key factors for thermal management. However, the enthalpies of most TRFs are not high, and the preparation methods are still at the laboratory scale. It remains a great challenge to use industrial spinning equipment to achieve continuous processing of TRFs with excellent thermal and mechanical properties. Here, polyamide 6 (PA6) based TRFs with a sheath-core structure were prepared by bicomponent melt-spinning. The sheath-core TRF (TRFsc) are composed of PA6 as sheath and functional PA6 as core, which are filled with the shape stable phase change materials (ssPCM), dendritic silica@polyethylene glycol (SiO2@PEG). With the aid of the sheath structure, the filling content of SiO2@PEG can reach 30 ​%, so that the enthalpy of the TRFs can be as high as 21.3 ​J/g. The ultra-high enthalpy guarantees the temperature regulation ability during the alternating process of cooling and heating. In hot environment, the temperature regulation time is 6.59 ​min, and the temperature difference is 12.93 ​°C. In addition, the mechanical strength of the prepared TRFsc reaches 2.26 cN/dtex, which can fully meet its application in the field of thermal management textiles and devices to manage the temperature regulation of the human body or precision equipment, etc.

Abstract Testicular cancer (TCa) is a rare but impactful malignancy that primarily affects young men. Understanding the mortality rate of TCa is crucial for improving prevention and treatment strategies to reduce the risk of death among patients. We obtained TCa mortality data by place (5 countries), age (20–79 years), and year (1990–2019) from the Global Burden of Disease Study 2019. Age-period-cohort model was used to estimate the net drift, local drift, age effects, period and cohort effects. In 2019, the global mortality of TCa increased to 10842 (95% UI 9961, 11902), with an increase of 50.08% compared to 1990.The all-age mortality rate for TCa in 2019 increased from 0.17/100,000 (95% UI 0.13, 0.20) in China to 0.48/100,000 (95% UI 0.38, 0.59) in Russian Federation, whereas the age-standardized mortality rate in 2019 was highest in the South Africa 0.47/100,000 (95% UI 0.42, 0.53) and lowest in the China 0.16/100,000 (95% UI 0.13, 0.19). China's aging population shifts mortality patterns towards the elderly, while in Russian Federation, young individuals are primarily affected by the distribution of deaths. To address divergent TCa mortality advancements in BRICS countries, we propose a contextually adaptive and resource-conscious approach to prioritize TCa prevention. Tailoring strategies to contextual diversity, including policy frameworks, human resources, and financial capacities, will enhance targeted interventions and effectiveness in reducing TCa mortality.

Abstract Optical sensors with in-cell logic and memory capabilities offer new horizons in realizing machine vision beyond von Neumann architectures and have been attempted with two-dimensional materials, memristive oxides, phase-changing materials etc. Noting the unparalleled performance of superconductors with both quantum-limited optical sensitivities and ultra-wide spectrum coverage, here we report a superconducting memlogic long-wave infrared sensor based on the bistability in hysteretic superconductor-normal phase transition. Driven cooperatively by electrical and optical pulses, the device offers deterministic in-sensor switching between resistive and superconducting (hence dissipationless) states with persistence > 105 s. This results in a resilient reconfigurable memlogic system applicable for, e.g., encrypted communications. Besides, a high infrared sensitivity at 12.2 μm is achieved through its in-situ metamaterial perfect absorber design. Our work opens the avenue to realize all-in-one superconducting memlogic sensors, surpassing biological retina capabilities in both sensitivity and wavelength, and presents a groundbreaking opportunity to integrate visional perception capabilities into superconductor-based intelligent quantum machines.

Abstract Background The interplay between exosomes and the tumor microenvironment (TME) remains unclear. We investigated the influence of exosomes on the TME in hepatocellular carcinoma (HCC), focusing on their mRNA expression profile. Methods mRNA expression profiles of exosomes were obtained from exoRBase. RNA sequencing data from HCC patients’ tumors were acquired from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). An exosome mRNA-related risk score model of prognostic value was established. The patients in the two databases were divided into high- and low-risk groups based on the median risk score value, and used to validate one another. Functional enrichment analysis was performed based on a differential gene prognosis model (DGPM). CIBERSORT was used to assess the abundance of immune cells in the TME. The correlation between the expression levels of immune checkpoint-related genes and DGPM was analyzed alongside the prediction value to drug sensitivity. Results A prognostic exosome mRNA-related 4-gene signature (DYNC1H1, PRKDC, CCDC88A, and ADAMTS5) was constructed and validated. A prognostic nomogram had prognostic ability for HCC. The genes for this model are involved in extracellular matrix, extracellular matrix (ECM)-receptor interaction, and the PI3K-Akt signaling pathway. Expression of genes here had a positive correlation with immune cell infiltration in the TME. Conclusions Our study results demonstrate that an exosome mRNA-related risk model can be established in HCC, highlighting the functional significance of the molecules in prognosis and risk stratification.

Abstract Background Placenta accreta spectrum often leads to massive hemorrhage and even maternal shock and death. This study aims to identify whether cervical length and cervical area measured by magnetic resonance imaging correlate with massive hemorrhage in patients with placenta accreta spectrum. Methods The study was conducted at our hospital, and 158 placenta previa patients with placenta accreta spectrum underwent preoperative magnetic resonance imaging examination were included. The cervical length and cervical area were measured and evaluated their ability to identify massive hemorrhage in patients with placenta accreta spectrum. Results The cervical length and area in patients with massive hemorrhage were both significantly smaller than those in patients without massive hemorrhage. The results of multivariate analysis show that cervical length and cervical area were significantly associated with massive hemorrhage. In all patients, a negative linear was found between cervical length and amount of blood loss (r =−0.613), and between cervical area and amount of blood loss (r =−0.629). Combined with cervical length and cervical area, the sensitivity, specificity, and the area under the curve for the predictive massive hemorrhage were 88.618%, 90.209%, and 0.890, respectively. Conclusion The cervical length and area might be used to recognize massive hemorrhage in placenta previa patients with placenta accreta spectrum.

Highlights An interactive electronic system inspired by the temperature self-regulation of human skin. Heat stimulation therapy and temperature monitoring during dynamic wound healing. Mechanism of temperature self-regulation during dynamic wound healing.

Abstract Background The COVID-19 pandemic has significantly increased the risk of burnout among frontline nurses. However, the prevalence of burnout and its associated factors in the post-pandemic era remain unclear. This research aims to investigate burnout prevalence among frontline nurses in the post-pandemic period and pinpoint associated determinants in China. Methods From April to July 2023, a cross-sectional study was carried out across multiple centers, focusing on frontline nurses who had been actively involved in the COVID-19 pandemic. The data collection was done via an online platform. The Maslach Burnout Inventory-Human Services Survey was utilized to evaluate symptoms of burnout. A multivariable logistic regression analysis was used to pinpoint factors associated with burnout. Results Of the 2210 frontline nurses who participated, 75.38% scored over the cut-off for burnout. Multivariable logistic regression revealed that factors like being female [odds ratio (OR) = 0.41, 95%CI = 0.29–0.58] and exercising 1–2 times weekly[OR = 0.53, 95%CI = 0.42–0.67] were protective factors against burnout. Conversely, having 10 or more night shifts per month[OR = 1.99, 95%CI = 1.39–2.84], holding a master’s degree or higher[OR = 2.86, 95% CI = 1.59–5.15], poor health status[OR = 2.43, 95% CI = 1.93–3.08] and [OR = 2.82, 95%CI = 1.80–4.43], under virus infection[OR = 7.12, 95%CI = 2.10-24.17], and elevated work-related stress[OR = 1.53, 95% CI = 1.17-2.00] were all associated with an elevated risk of burnout. Conclusion Our findings indicate that post-pandemic burnout among frontline nurses is influenced by several factors, including gender, monthly night shift frequency, academic qualifications, weekly exercise frequency, health condition, and viral infection history. These insights can inform interventions aimed at safeguarding the mental well-being of frontline nurses in the post-pandemic period.

With increased precipitation and meltwater, most lakes on the Tibetan Plateau have expanded rapidly. However, the impact of erosion and sedimentation following lake expansion remains unclear. Using Lexiewudan and Yanhu Lakes as examples, we created a water depth inversion model using random forest method and combined it with lake bathymetric data and Landsat images and analyzed changes in underwater topography using SRTM and ICESat-2 data. The average water depths of two lakes were 5.92 and 9.82 m, and the root mean square error of inversion values were 0.85 and 0.93 m, respectively. Results showed that the underwater topography underwent considerable changes, in which at least half of the study areas experienced large topographic changes with 2–5 m. Lexiewudan Lake had a topographic change of more than 2 m in 61.28% of the total, while Yanhu Lake made up 69.78% of the total. The erosion and sedimentation volume of Lexiewudan Lake were 0.19 and 0.03 km3 and those of Yanhu Lake were 0.38 and 0.03 km3, respectively. Extensive underwater erosion and sedimentation are closely related to the original topography. Lake water movement, sediment transport, and permafrost degradation in flooded areas may also affect changes in underwater topography.

Light-flavor Baijiu (LFB) fermentation is a representative spontaneous mixed-culture solid-state fermentation process in which sorghum is used as the raw material. Raw materials and microorganisms are crucial to the flavor formation and quality of LFB. However, the microbial and physicochemical dynamics of different sorghum varieties during LFB fermentation, as well as their impact on flavor compounds are still largely unknown. Herein, PacBio single-molecule real-time (SMRT) sequencing and headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry (HS-SPME-GC–MS) were applied to investigate microbial community succession and volatile flavor formation in glutinous/non-glutinous sorghum-based fermented grains during LFB fermentation. Fermented grains made of glutinous sorghum Liangnuo No. 1 (GLN) had higher bacterial α-diversity and lower fungal α-diversity than those with fermented grains prepared with non-glutinous red sorghum (NRS) (p

“Green-covering and red-heart” Guanyin Tuqu (GRTQ), as a type of special fermentation starter, is characterized by the “green-covering” formed on the surface of Guanyin Tuqu (SQ) and the “red-heart” in the center of Guanyin Tuqu (CQ). However, the mechanisms that promote temporal succession in the GRTQ microbial ecology and the formation of “green-covering and red-heart” characteristics remain unclear. Herein, we correlated the temporal profiles of microbial community succession with the main environmental variables (temperature, moisture, and acidity) and spatial position (center and surface) in GRTQ throughout fermentation. According to the results of high-throughput sequencing and culture-dependent methods, the microbial communities in the CQ and SQ demonstrated functional complementarity. For instance, the bacterial richness index of the CQ was greater than that of SQ, and the fungal richness index of the SQ was greater than that of CQ at the later stage of fermentation. Furthermore, Saccharomycopsis, Saccharomyces, Aspergillus, Monascus, Lactobacillus, Bacillus, Rhodanobacter, and Chitinophaga were identified as the dominant microorganisms in the center, while the surface was represented by Saccharomycopsis, Aspergillus, Monascus, Lactobacillus, Acetobacter, and Weissella. By revealing the physiological characteristics of core microorganisms at different spatial positions of GRTQ, such as Aspergillus clavatus and Monascus purpureus, as well as their interactions with environmental factors, we elucidated the color formation mechanism behind the phenomenon of “green” outside and “red” inside. This study provides fundamental information support for optimizing the production process of GRTQ.

Early weaning leads to weaning stress in calves, which hinders healthy growth and development. As an excellent sweetener applied in food, steviol glycosides (STE) has also been shown to exhibit positive biological activity in monogastric animals. Therefore, this study aimed to evaluate the impact of incorporating STE as a dietary supplement on rumen development, fermentation, and microbiota of rumen in weaned calves. This study selected 24 healthy Holstein bull calves and randomly allocated them into two groups (CON and STE). The results indicated that supplementation STE group improved rumen development in weaned calves, as demonstrated by a marked increase in the weight of the rumen, as well as the length and surface area of the rumen papilla. Compared with the CON group, the concentrations of total volatile fatty acids (TVFA), propionate, butyrate, and valerate were higher in the STE group. Moreover, STE treatment increased the relative abundance of Firmicutes and Actinobacteria at the phylum level. At the genus level, the STE group showed a significantly increased relative abundance of Succiniclasticum, Lachnospiraceae_NK3A20_group, and Olsenella, and a decreased relative abundance of Acinetobacter compared to the CON group. Pusillimonas, Lachnospiraceae_NK3A20_group, Olsenella, and Succiniclasticum were significantly enriched in rumen chyme after supplementation with STE, as demonstrated by LEfSe analysis. Overall, our findings revealed that rumen bacterial communities altered in response to the dietary supplementation with STE, and some bacterial taxa in these communities may have positive effects on rumen development during this period.

Background: There is no consensus on the timing of immunotherapeutic strategies for the first-episode anti-myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) associated disorders (MOGAD) presenting with isolated optic neuritis (ON). Objective: To investigate the optimal timing of intravenous methylprednisolone therapy (IVMP) and necessity of immunosuppressive therapy for the first-episode isolated MOG-IgG associated ON (iMOG-ON). Methods: Adult patients with the first-episode iMOG-ON were enrolled. Primary outcomes were best-corrected visual acuity (BCVA) at last follow-up (i.e. final BCVA) and relapse, and their predictors were assessed by multivariate analysis. Results: 62 patients were included. Logistic regression analysis revealed BCVA at the time of IVMP (odds ratio: 0.463 (95 % confidence interval (CI) 0.310-0.714) was a factor predictive of regaining a final BCVA of 0.0 logMAR vision, and its Youden optimal criterion was

BackgroundRenshen Yangrong decoction (RSYRD) has been shown therapeutic effects on secondary malaise and fatigue (SMF). However, to date, its bioactive ingredients and potential targets remain unclear.PurposeThe purpose of this study is to assess the potential ingredients and targets of RSYRD on SMF through a comprehensive strategy integrating network pharmacology, Mendelian randomization as well as molecular docking verification.MethodsSearch for potential active ingredients and corresponding protein targets of RSYRD on TCMSP and BATMAN-TCM for network pharmacology analysis. Mendelian randomization (MR) was performed to find therapeutic targets for SMF. The eQTLGen Consortium (sample sizes: 31,684) provided data on cis-expression quantitative trait loci (cis-eQTL, exposure). The summary data on SMF (outcome) from genome-wide association studies (GWAS) were gathered from the MRC-IEU Consortium (sample sizes: 463,010). We built a target interaction network between the probable active ingredient targets of RSYRD and the therapeutic targets of SMF. We next used drug prediction and molecular docking to confirm the therapeutic value of the therapeutic targets.ResultsIn RSYRD, network pharmacology investigations revealed 193 possible active compounds and 234 associated protein targets. The genetically predicted amounts of 176 proteins were related to SMF risk in the MR analysis. Thirty-seven overlapping targets for RSYRD in treating SMF, among which six (NOS3, GAA, IMPA1, P4HTM, RB1, and SLC16A1) were prioritized with the most convincing evidence. Finally, the 14 active ingredients of RSYRD were identified as potential drug molecules. The strong affinity between active components and putative protein targets was established by molecular docking.ConclusionThis study revealed several active components and possible RSYRD protein targets for the therapy of SMF and provided novel insights into the feasibility of using Mendelian randomization for causal inference between Chinese medical formula and disease.

Abstract Background and aim Reprogramming microorganisms to enhance the production of metabolites is a part of contemporary synthetic biology, which relies on the availability of genetic tools to successfully manipulate the bacteria. Methylorubrum extorquens AM1 is a platform microorganism used to convert C1 compounds into various value-added products. However, the repertoire of available plasmids to conveniently and quickly fine-tune the expression of multiple genes in this strain is extremely limited compared with other model microorganisms such as Escherichia coli. Thus, this study aimed to integrate existing technologies, such as transposon-mediated chromosomal integration and cre-lox-mediated recombination, to achieve the diversified expression of target genes through multiple chromosomal insertions in M. extorquens AM1. Results A single plasmid toolkit, pSL-TP-cre-km, containing a miniHimar1 transposon and an inducible cre-lox71/lox66 system, was constructed and characterized for its multiple chromosomal integration capacity. A co-transcribed mcr-egfp cassette [for the production of 3-hydroxypropionic acid (3-HP) and a reporting green fluorescent protein] was added to construct pTP-cre-mcr-egfp for evaluating its utility in mediating the expression of heterologous genes, resulting in the production of 3-HP with a titer of 34.7–55.2 mg/L by two chromosomal integration copies. Furthermore, in association with the expression of plasmid-based mcr, 3-HP production increased to 65.5–92.4 mg/L. Conclusions This study used a multi-round chromosomal integration system based on cre-lox71/lox66 and a transposon to construct a single constructed vector. A heterologous mcr gene was introduced through this vector, and high expression of 3-hydroxypropionic acid was achieved in M. extorquens. This study provided an efficient genetic tool for manipulating M. extorquens, which not only help increase the expression of heterologous genes in M. extorquens but also provide a reference for strains lacking genetic manipulation vectors.

Abstract Background Placenta accreta spectrum (PAS) carries an increased risk of maternal-fetal mortality and morbidity, and magnetic resonance imaging (MRI) features for PAS have been used for preoperative identification. This study aims to investigate the role of placental volume evaluated by MRI in identifying PAS in pregnant women with complete placenta previa. Methods Totally 163 cases of complete placenta previa pregnant women with a history of cesarean section underwent MRI for suspected PAS were included. We categorized the patients into two groups according to the presence or absence of PAS, and the maternal-fetal perinatal outcomes and placental volume analyzed by 3D Slice software were compared. Results There were significantly more gravidity, parity, and number of previous cesarean delivery in the PAS group (P

ABSTRACTFenjie Island, as an isolated island, has evolved into a 5A-rated tourist destination. However, in recent years, due to the one-sided pursuit of economic gains, the island has continuously developed its tourism resources, resulting in over-exploitation of resources and significant ecological impacts. This study meticulously scrutinizes tourism-related carbon emissions in comparison to the island's natural capacities. Comprehensive research spans ships, accommodations, dining, and various activities, revealing emissions surpassing nature's limits. The study delves into intricate emission models, emphasizing energy-intensive sectors.Empirical findings underscore a pressing disparity: daily emissions far exceed the island's absorption and purification capacities, underscoring the urgency for intervention. To restore equilibrium, the study proposes recalibrating tourism by aligning it with the island's natural resources. Forest and seawater capacities emerge as vital benchmarks for sustainable tourist numbers. Proposed strategies emphasize rigorous energy conservation and emissions reduction, offering a roadmap for sustainable development.These robust findings provide an essential scientific basis for Fenjie Island's future. They illuminate a path toward balanced growth, crucial for harmonizing economic prosperity and environmental preservation. Informed by this research, policymakers can steer the island's trajectory, ensuring a sustainable, thriving future amidst the challenges of modern tourism..

Salinity is an essential factor of lake water environments and aquatic systems. It is also sensitive to climatic changes and human activities based on concentration variations of solved minerals. However, there are few consecutively temporal studies on lake salinity variations on the Tibetan Plateau because the harsh environmental conditions make it difficult to carry out in-situ observations for several lakes. In this study, we constructed a remote sensing retrieval model for lake salinity based on 87 in-situ lake investigations; moreover, interannual lake salinity and associated variations from 152 lakes larger than 50 km2 were analyzed on the Tibetan Plateau. A significant decreasing trend in lake salinity was observed between 2000 and 2019 (p

We contribute transcriptomic data for two species of Ostracoda, an early-diverged group of small-sized pancrustaceans. Data include new reference transcriptomes for two asexual non-marine species (Dolerocypris sinensis and Heterocypris aff. salina), as well as single-specimen transcriptomic data that served to analyse gene expression across four developmental stages in D. sinensis. Data are evaluated by computing gene expression profiles of the different developmental stages which consistently placed eggs and small larvae (at the stage of instar A-8) similar to each other, and apart from adults which were distinct from all other developmental stages but closest to large larvae (instar A-4). We further evaluated the transcriptomic data with two newly sequenced low-coverage genomes of the target species. The new data thus document the feasibility of obtaining reliable transcriptomic data from single specimens – even eggs – of these small metazoans.

Abstract Hydroxylated isoprenoid GDGTs (OH‐GDGTs) have emerged as a novel tool for reconstructing sea surface temperatures. However, when using marine OH‐GDGT calibration in lacustrine settings, it leads to a significant overestimation of temperatures, emphasizing the necessity for a thorough examination of OH‐GDGTs in lakes. Here, we investigated OH‐GDGT distributions in surface sediments from 65 lakes in West China and compiled published Asian lake and global marine OH‐GDGT data sets. Among all GDGT‐based indices, RI‐OH showed the strongest correlation with temperature across Asian lakes. The RI‐OH value was higher in lakes than in marine sediments, likely due to differences in the composition of Group 1.1a thaumarchaeotal species between the two settings. The first RI‐OH temperature calibration for lakes was developed and it addressed the issue of temperature overestimation when applied to both water column and sediment core, highlighting the potential of OH‐GDGTs as a new terrestrial paleothermometer.

Background and aim:Vancomycin, a glycopeptide antimicrobial drug. PPK has problems such as difficulty in accurately reflecting inter-individual differences, and the PPK model may not be accurate enough to predict individual pharmacokinetic parameters. Therefore, the aim of this study is to investigate whether the application of machine learning combined with the PPK method can improve the prediction of vancomycin CL in adult Chinese patients.Methods:In the first step, a vancomycin CL prediction model for Chinese adult patients is given by PPK and Hamilton Monte Carlo sampling is used to obtain the reference CL of 1,000 patients; the second step is to obtain the final prediction model by machine learning using an appropriate model for the predictive factor and the reference CL; and the third step is to randomly select, in the simulated data, a total of 250 patients for prediction effect evaluation.Results:XGBoost model is selected as final machine learning model. More than four-fifths of the subjects’ predictive values regarding vancomycin CL are improved by machine learning combined with PPK. Machine learning combined with PPK models is more stable in performance than the PPK method alone for predicting models.Conclusion:The first combination of PPK and machine learning for predictive modeling of vancomycin clearance in adult patients. It provides a reference for clinical pharmacists or clinicians to optimize the initial dosage given to ensure the effectiveness and safety of drug therapy for each patient.

Abstract Venous thromboembolism (VTE) is a multifactorial disease, and pulmonary hypertension (PH) is a serious condition characterized by pulmonary vascular remodeling leading with increased pulmonary vascular resistance, ultimately leading to right heart failure and death. Although VTE and PH have distinct primary etiologies, they share some pathophysiologic similarities such as dysfunctional vasculature and thrombosis. In both conditions there is solid evidence that EVs derived from a variety of cell types including platelets, monocytes, endothelial cells and smooth muscle cells contribute to vascular endothelial dysfunction, inflammation, thrombosis, cellular activation and communications. However, the roles and importance of EVs substantially differ between studies depending on experimental conditions and parent cell origins of EVs that modify the nature of their cargo. Numerous studies have confirmed that EVs contribute to the pathophysiology of VTE and PH and increased levels of various EVs in relation with the severity of VTE and PH, confirming its potential pathophysiological role and its utility as a biomarker of disease severity and as potential therapeutic targets. Graphical Abstract

Abstract Preeclampsia (PE) is a significant threat to all pregnancies that is highly associated with maternal mortality and developmental disorders in infants. However, the etiopathogenesis of this condition remains unclear. This study aims to explore the regulatory roles of long noncoding RNAs (lncRNAs) and the mediated competing endogenous RNAs (ceRNA) in the etiopathogenesis of PE through analysis of lncRNA expression patterns in PE and healthy pregnant women (HPW), as well as the construction of lncRNA-mediated ceRNA regulatory networks using bioinformatics. A total of 896 significant differentially expressed lncRNAs, including 586 upregulated lncRNAs and 310 downregulated lncRNAs, were identified in comparison between PE and HPW. Analysis of these differential expressed lncRNAs revealed their predominant enrichment in molecular functions such as sphingosine-1-phosphate phosphatase activity, lipid phosphatase activity, phosphatidate phosphatase activity, thymidylate kinase activity, and UMP kinase activity. Moreover, these differential expressed lncRNAs were predominantly enriched in KEGG analyses such as fat digestion and absorption, lysine degradation, ether lipid metabolism, glycerolipid metabolism, and sphingolipid metabolism. Two ceRNA regulatory networks were constructed based on ceRNA score, including one that had 31 upregulated lncRNAs, 11 downregulated miRNAs, and 34 upregulated mRNAs, while the other contained 128 downregulated lncRNAs, 40 upregulated miRNAs, and 113 downregulated mRNAs. These results may provide a clue to explore the roles of lncRNAs in the etiopathogenesis of PE.

Mulberry leaf tea (MT) is a popular Chinese food with nutrition and medicinal functions. Solid-state fermentation with Eurotium cristatum of MT (FMT) can improve their quality. Differences in chromaticity, taste properties, and flavor characteristics were analyzed to evaluate the improvements of the sensory quality of FMT. After fermentation, the color of the tea infusion changed. The E-tongue evaluation results showed a significant decrease in unpleasant taste properties such as sourness, bitterness, astringency, and aftertaste-bitterness, while umami and saltiness taste properties were enhanced post-fermentation. Aroma-active compounds in MT and FMT were identified and characterized. A total of 25 key aroma-active compounds were screened in MT, and 2-pentylfuran showed the highest relative odor activity value (ROAV). A total of 26 key aroma-active compounds were identified in FMT, and the newly formed compound 1-octen-3-one showed the highest ROAV, which contributed to FMT’s unique mushroom, herbal, and earthy flavor attributes. 1-octen-3-one, (E)-2-nonenal, trimethyl-pyrazine, 2-pentylfuran, and heptanal were screened as the potential markers that contributed to flavor differences between MT and FMT. E. cristatum fermentation significantly altered the sensory properties and flavor compounds of MT. This study provides valuable insights into the sensory qualities of MT and FMT, offering a theoretical basis for the development of FMT products.

Abstract Design A two-round Delphi survey was conducted to seek opinions from experts about the index system for the evaluation of training courses of clinical nursing staff’s information literacy. Besides, a non-randomized controlled experimental study was adopted to check the application effect of the training courses. Aims This study intended to construct a training course of information literacy for clinical nurses, train nurses in order to improve their information literacy level and provide theoretical reference for the training of information literacy courses for clinical nurses. Methods Two rounds of Delphi study were conducted for the study among 26 clinical medical and nursing experts as well as educational experts from 5 different provinces and cities in China. From July 2022 to October 2022, a total of 84 clinical nurses from two hospitals were selected by the convenience sampling method, of which the nurses in one hospital were the control group and the nurses in the other hospital were the observation group. 42 nurses in the observation group were trained by the constructed information literacy training course. Questionnaire evaluation was used to compare the differences in the level of information literacy of nurses and the training effect between the two groups. Results The results of the Delphi consultation showed that the expert’s judgment coefficient was 0.958, the expert’s familiarity was 0.946, and the expert’s authority coefficient was 0.952. Finally, a training course of information literacy for clinical nurses with 4 course categories and 45 specific course contents was formed. Among them, nursing information awareness included 7 courses, nursing information knowledge 15 courses, nursing information ability 19 courses, and nursing information ethics 4 courses. The results of the empirical study showed that the information literacy level of the nurses in the observation group after the training of the information literacy course was improved, and the scores in nursing information awareness, nursing information knowledge, nursing information ability, and information ethics were significantly higher than those in the control group after training (P

BackgroundHay fever, characterized by seasonal allergic reactions, poses a significant health challenge. Existing therapies encompass standard drug regimens, biological agents, and specific immunotherapy. This study aims to assess and compare the effectiveness of anti-IgE (omalizumab), medication therapy, and subcutaneous immunotherapy (SCIT) for hay fever.MethodsConducted as a retrospective cohort study, this research involved 98 outpatient hay fever patients who underwent routine medication, omalizumab treatment, or SCIT before the onset of the spring pollen season. A follow-up was performed one month after the start of the pollen season. The comprehensive symptoms and drug scores were used to evaluate patients with different intervention methods, facilitating a comparative analysis of therapeutic outcomes.ResultsCompared with before treatment, the symptoms of patients treated with the three methods were all significantly relieved, and the medication score were significantly reduced. Patients treated with omalizumab demonstrated higher symptoms and medication scores than SCIT group before treatment, but similar scores after treatment, which were both lower than medicine treatment group. After treatment with omalizumab or SCIT, patients in both groups had significantly lower medication scores than the medication group and were close to no longer using medication for symptom relief. The mountain juniper-sIgE was significantly higher after treatment than before treatment in both medicine treatment group and omalizumab treatment group.ConclusionOmalizumab and SCIT offer superior effects than medication therapy in hay fever patients.

Acne vulgaris, one of the most common skin diseases, is a chronic cutaneous inflammation of the upper pilosebaceous unit (PSU) with complex pathogenesis. Inflammation plays a central role in the pathogenesis of acne vulgaris. During the inflammatory process, the innate and adaptive immune systems are coordinately activated to induce immune responses. Understanding the infiltration and cytokine secretion of differential cells in acne lesions, especially in the early stages of inflammation, will provide an insight into the pathogenesis of acne. The purpose of this review is to synthesize the association of different cell types with inflammation in early acne vulgaris and provide a comprehensive understanding of skin inflammation and immune responses.

Lake ecosystems on the Tibetan Plateau (TP) are highly susceptible to external input owing to their fragile environment. However, less study has been done to focus the direct influences of anthropogenic activities on the lake sediments by human activities. In this study, we performed the first large-scale investigation to use the fecal stanol proxies in lake surface sediments to assess the impact of human and herbivorous feces on TP lakes. The 75 investigated lakes were divided into three types (I, II, and III) according to cluster analysis of the fecal stanol ratios R1′ and R2′. Fecal stanols in type I lake surface sediments originate from a mixture of herbivorous and human feces; fecal stanols in type II lake surface sediments primarily originate from herbivorous feces with minimal human feces. In contrast, fecal stanols in type III lake surface sediments are mainly derived from herbivorous feces (coprostanol concentration > 100 ng/g), a mixed source of herbivorous feces and cholesterol reduction (coprostanol concentration of 10–100 ng/g), and in situ reduction of cholesterol (coprostanol concentration

Abstract In the fast‐evolving landscape of decentralized and personalized healthcare, the need for multimodal biosensing systems that integrate seamlessly with the human body is growing rapidly. This presents a significant challenge in devising ultraflexible configurations that can accommodate multiple sensors and designing high‐performance sensing components that remain stable over long periods. To overcome these challenges, ultraflexible organic photodetectors (OPDs) that exhibit exceptional performance under near‐infrared illumination while maintaining long‐term stability are developed. These ultraflexible OPDs demonstrate a photoresponsivity of 0.53 A W−1 under 940 nm, shot‐noise‐limited specific detectivity of 3.4 × 1013 Jones, and cut‐off response frequency beyond 1 MHz at −3 dB. As a result, the flexible photoplethysmography sensor boasts a high signal‐to‐noise ratio and stable peak‐to‐peak amplitude under hypoxic and hypoperfusion conditions, outperforming commercial finger pulse oximeters. This ensures precise extraction of blood oxygen saturation in dynamic working conditions. Ultraflexible OPDs are further integrated with conductive polymer electrodes on an ultrathin hydrogel substrate, allowing for direct interface with soft and dynamic skin. This skin‐integrated sensing platform provides accurate measurement of photoelectric and biopotential signals in a time‐synchronized manner, reproducing the functionality of conventional technologies without their inherent limitations.

IntroductionNurses are more likely to experience anxiety following the coronavirus 2019 epidemic. Anxiety could compromise nurses’ work efficiency and diminish their professional commitment. This study aims to investigate nurses’ anxiety prevalence and related factors following the pandemic in multiple hospitals across China.MethodsAn online survey was conducted from April 16 to July 3, 2023, targeting frontline nurses who had actively participated in China. Anxiety and depression symptoms were assessed using the Self-rating Anxiety Scale and the Self-rating Depression Scale (SDS), respectively. Multivariable logistic regression analysis was employed to identify factors linked with anxiety.ResultsA total of 2,210 frontline nurses participated in the study. Overall, 65.07% of participants displayed clinically significant anxiety symptoms. Multivariable logistic regression revealed that nurses living with their families [2.52(95% CI: 1.68–3.77)] and those with higher SDS scores [1.26(95% CI: 1.24–1.29)] faced an elevated risk of anxiety. Conversely, female nurses [0.02(95% CI: 0.00–0.90)] and those who had recovered from infection [0.05(95%CI: 0.07–0.18)] demonstrated lower rates of anxiety.DiscussionThis study highlights the association between SDS score, gender, virus infection, living arrangements and anxiety. Frontline nurses need to be provided with emotional support to prevent anxiety. These insights can guide interventions to protect the mental well-being of frontline nurses in the post-pandemic period.

ABSTRACTPhase-change memory (PCM), recently developed as the storage-class memory in a computer system, is a new non-volatile memory technology. In addition, the applications of PCM in a non-von Neumann computing, such as neuromorphic computing and in-memory computing, are being investigated. Although PCM-based devices have been extensively studied, several concerns regarding the electrical, thermal, and structural dynamics of phase-change devices remain. In this article, aiming at PCM devices, a comprehensive review of PCM materials is provided, including the primary PCM device mechanics that underpin read and write operations, physics-based modeling initiatives and experimental characterization of the many features examined in nanoscale PCM devices. Finally, this review will propose a prognosis on a few unsolved challenges and highlight research areas of further investigation.

ABSTRACTIt is critical to determine the real-world performance of vaccines against coronavirus disease 2019 (COVID-19) so that appropriate treatments and policies can be implemented. There was a rapid wave of infections by the Omicron variant in Jilin Province (China) during spring 2022. We examined the effectiveness of inactivated vaccines against Omicron using real-world data from this epidemic. This retrospective case-case study of vaccine effectiveness (VE) examined infected patients who were quarantined and treated from April 16 to June 8, 2022 and responded to an electronic questionnaire. Data were analyzed by univariable and multivariable analyses. A total of 2968 cases with SARS-CoV-2 infections (asymptomatic: 1061, mild disease: 1763, pneumonia: 126, severe disease: 18) were enrolled in the study. Multivariable regression indicated that the risk for pneumonia or severe disease was greater in those who were older or had underlying diseases, but was less in those who received COVID-19 vaccines. Relative to no vaccination, VE against the composite of pneumonia and severe disease was significant for those who received 2 doses (60.1%, 95%CI: 40.0%, 73.5%) or 3 doses (68.1%, 95%CI: 44.6%, 81.7%), and VE was similar in the subgroups of males and females. However, VE against the composite of all three classes of symptomatic diseases was not significant overall, nor after stratification by sex. There was no statistical difference in the VE of vaccines from different manufacturers. The inactivated COVID-19 vaccines protected patients against pneumonia and severe disease from Omicron infection, and booster vaccination enhanced this effect.

During the International Workshop on Soil Erosion and Riverine Sediment in Mountainous Regions held in November 2022, scientists from many countries shared their state-of-the-art knowledge and brainstormed to improve scientific understanding for coping with climate change and anthropogenic impacts. Information summarized in this discussion includes proposed key scientific questions and suggested joint actions to reduce soil erosion and riverine sediment problems in mountainous regions.

Abstract Introduction Aberrant gene expression is a key mechanism underlying pulmonary hypertension (PH) development. The alterations of genomic chromatin accessibility and their relationship with the aberrant gene expressions in PH are poorly understood. We used bulk Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing (RNA-seq) in pulmonary artery smooth muscle cells (PASMCs) of chronic hypoxia-exposed rats mimicking group 3 human PH. Methods Adult Sprague Dawley rats were commercially obtained from Hunan SJA (Hunan SJA Laboratory Animal Co., Changsha, China) and randomizedly allocated into four groups exposing to nomobaric hypoxia or normoxia for 1 or 28 days respectively. After the assessment of pulmonary hemodynamics, smooth muscle cells were isolated from intralobular arteries and simultaneously subjected to bulk Assay of ATAC-seq and RNA-seq. Results Hypoxic exposure for continuous 28-days, but not for 1-day, induced established PH phenotypes in rats. ATAC-seq revealed a major distribution of differential accessibility regions (DARs) annotated to the genome in out-of-promoter regions, following 1-day or 28-days hypoxia. 1188 DAR-associated genes and 378 differentially expressed genes (DEGs) were identified in rats after exposure to 1-day hypoxia, while 238 DAR-associated genes and 452 DEGs for 28-days hypoxia. Most of the DAR-associated genes or DEGs in 1-day did not overlap with that of 28-days hypoxia. A Pearson correlation analysis indicated no significant correlation between ATAC-seq and RNA-seq. Conclusions The alterations in genomic chromatin accessibility and genes expression of PASMCs in the initial stage of hypoxia are distinct from the established stage of hypoxia-induced PH. The genomic differential accessibility regions may not be the main mechanisms directly underlying the differentially expressed genes observed either in the initial or established stages of PH. Thus the time-course alterations of gene expression and their possible indirect link with genomic chromatin accessibility warrant more attention in mechanistic study of pulmonary hypertension.

Abstract Purpose Pyroptosis, a type of programmed cell death, is implicated in the tumorigenesis, development and migration of cancer, which can be regulated by long non‐coding RNAs (lncRNAs). Our research aimed to investigate the prognostic role of pyroptosis‐related lncRNAs and the relationship to the tumor immune microenvironment through bioinformatics analysis. Methods The clinical and RNA‐sequencing data of bladder cancer patients were downloaded from The Cancer Genome Atlas (TCGA). And 412 bladder cancer subjects with clinical information were divided into training and testing cohort. And 52 reported pyroptosis‐related genes were used to screen pyroptosis‐related lncRNAs. A pyroptosis‐related lncRNA signature was constructed based on Cox regression analyses. Results A 9‐pyroptosis‐related‐lncRNA signature was identified to separate patients with bladder cancer into two groups. The prognosis of bladder cancer patients in the high‐risk group was significantly inferior compared with those in the low‐risk group. Risk scores were validated to develop an independent prognostic indicator based on multivariate Cox regression analysis. Receiver operating characteristic curve (ROC) analysis examined the signature on overall survival. The area under time‐dependent ROC curve (AUC) at 1‐, 3, and 5‐years measured 0.747, 0.783, and 0.768, respectively. Analysis of the immune landscape and PD‐L1 expression showed that PD‐L1 is upregulated in the high‐risk group. The immunocyte subtypes of the two groups were different. Conclusion A novel pyroptosis‐related lncRNA signature was identified with prognostic value for bladder cancer patients. Pyroptosis‐related lncRNAs have a potential role in cancer immunology and may serve as prognostic or therapeutic targets.

Taking Zhahan village in Qiongzhong County, Hainan, as an example, and based on its 160,000 tourist arrivals in 2019 and taking into account the real circumstances of Hainan, this research composes the emission models of carbon emissions from tourism transportation, tourism accommodation, tourism catering, other tourism activities and pollutants in this village. The outcomes indicate that Zhahan village's tourism catering consumes the most energy and emits the most carbon, accounting for 53.95% of all carbon emissions. Furthermore, the emission of tourism accommodation is the second, occupying 24.13%. Then, its tourism waste emission is the third, constituting 13.61%. In addition, its annual sewage discharge from tourism activities amounts to 15,144 t. This article promoted 1MW photovoltaic and 10 square solar hot water in the entire village, scientifically developing the evaluation system of rural tourism carbon emission, and making a low carbon brand of emission reduction coupling. The research and operation can be replicated and extended to enable the harmonious development of tourism development and organic unity of energy resource utilization.

Over the past decades, the cryosphere has changed significantly in High Mountain Asia (HMA), leading to multiple natural hazards such as rock–ice avalanches, glacier collapse, debris flows, landslides, and glacial lake outburst floods (GLOFs). Monitoring cryosphere change and evaluating its hydrological effects are essential for studying climate change, the hydrological cycle, water resource management, and natural disaster mitigation and prevention. However, knowledge gaps, data uncertainties, and other substantial challenges limit comprehensive research in climate–cryosphere–hydrology–hazard systems. To address this, we provide an up-to-date, comprehensive, multidisciplinary review of remote sensing techniques in cryosphere studies, demonstrating primary methodologies for delineating glaciers and measuring geodetic glacier mass balance change, glacier thickness, glacier motion or ice velocity, snow extent and water equivalent, frozen ground or frozen soil, lake ice, and glacier-related hazards. The principal results and data achievements are summarized, including URL links for available products and related data platforms. We then describe the main challenges for cryosphere monitoring using satellite-based datasets. Among these challenges, the most significant limitations in accurate data inversion from remotely sensed data are attributed to the high uncertainties and inconsistent estimations due to rough terrain, the various techniques employed, data variability across the same regions (e.g., glacier mass balance change, snow depth retrieval, and the active layer thickness of frozen ground), and poor-quality optical images due to cloudy weather. The paucity of ground observations and validations with few long-term, continuous datasets also limits the utilization of satellite-based cryosphere studies and large-scale hydrological models. Lastly, we address potential breakthroughs in future studies, i.e., (1) outlining debris-covered glacier margins explicitly involving glacier areas in rough mountain shadows, (2) developing highly accurate snow depth retrieval methods by establishing a microwave emission model of snowpack in mountainous regions, (3) advancing techniques for subsurface complex freeze–thaw process observations from space, (4) filling knowledge gaps on scattering mechanisms varying with surface features (e.g., lake ice thickness and varying snow features on lake ice), and (5) improving and cross-verifying the data retrieval accuracy by combining different remote sensing techniques and physical models using machine learning methods and assimilation of multiple high-temporal-resolution datasets from multiple platforms. This comprehensive, multidisciplinary review highlights cryospheric studies incorporating spaceborne observations and hydrological models from diversified techniques/methodologies (e.g., multi-spectral optical data with thermal bands, SAR, InSAR, passive microwave, and altimetry), providing a valuable reference for what scientists have achieved in cryosphere change research and its hydrological effects on the Third Pole.

Lysozyme, a common antimicrobial agent, is widely used in the food, biopharmaceutical, chemical, and medicine fields. Rapid and effective isolation of lysozymes is an everlasting topic. In this work, ethylene vinyl alcohol (EVOH) copolymer nanofibrous membranes with a gradient porous structure used for lysozyme adsorption were prepared through layer-by-layer nanofiber wet-laying and a cost-efficient ultraviolet (UV)-assisted graft-modification method, where benzophenone was used as an initiator and 2-acrylamide-2-methylpropanesulfonic acid as a modifying monomer. As indicated in the Fourier Transform Infrared (FTIR) and X-ray photoelectric energy spectrometer (XPS) investigation, sulfonic acid groups were introduced on the surface of the modified nanofibrous membrane, which possessed the ability to adsorb lysozyme. Compared with membranes with homogenous porous structures, membranes with a gradient porous structure present higher static (335 mg/g) and dynamic adsorption capacities (216.3 mg/g). Meanwhile, the adsorption capacity remained high after five cycles of the adsorption–desorption process. The results can be attributed to the gradient porous structure rather than the highest porosity and specific surface area. This suggests that the membrane with comprehensive separation performance can be designed from the view of the transmembrane porous structure, which is of significance for the development of next-generation advanced chromatographic membranes.

MAPKKs, as one of the main members of the mitogen-activated protein kinase (MAPK) cascade pathway, are located in the middle of the cascade and are involved in many physiological processes of plant growth and development, as well as stress tolerance. Previous studies have found that StMAPKK5 is responsive to drought and salt stress. To further investigate the function and regulatory mechanism of StMAPKK5 in potato stress response, potato variety ‘Atlantic’ was subjected to drought and NaCl treatments, and the expression of the StMAPKK5 gene was detected by qRT-PCR. StMAPKK5 overexpression and RNA interference-mediated StMAPKK5 knockdown potato plants were constructed. The relative water content, superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities, as well as proline (Pro) and malondialdehyde (MDA) contents of plant leaves, were also assayed under drought and NaCl stress. The StMAPKK5 interacting proteins were identified and validated by yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC). The results showed that the expression of StMAPKK5 was significantly up-regulated under drought and NaCl stress conditions. The StMAPKK5 protein was localized in the nucleus, cytoplasm, and cell membrane. The expression of StMAPKK5 affected the relative water content, the enzymatic activities of SOD, CAT, and POD, and the proline and MDA contents of potatoes under drought and salt stress conditions. These results suggest that StMAPKK5 plays a significant role in regulating drought and salt tolerance in potato crop. Yeast two-hybrid (Y2H) screening identified four interacting proteins: StMYB19, StZFP8, StPUB-like, and StSKIP19. BiFC confirmed the authenticity of the interactions. These findings suggest that StMAPKK5 is crucial for potato growth, development, and response to adversity.

Background: Acquired resistance to targeted drugs is a major challenge in cancer. The drug-tolerant state has been proposed to be an initial step towards acquisition of real drug-resistance. Drug tolerant persister (DTP) cells are purported to survive during treatment and stay dormant for several years. Single cell sequencing can provide a comprehensive landscape of gene expression in DTP cells, which can facilitate investigation of heterogeneity of a drug tolerant state and identification of new anticancer targets. Methods: The genetic profiling of DTPs was explored by integrating Gene Expression Omnibus (GEO) datasets, and a prognostic signature of DTP-related genes (DTPRGs) in lung adenocarcinoma of TCGA LUAD cohort was constructed. The scores of infiltrating immune cells were calculated and activity of immune-related pathways was evaluated by single-sample gene set enrichment analysis (ssGSEA). Functional enrichment analysis of the DTPRGs between low- and high-risk groups was performed. Immune cell subtypes and immune-related pathways were analyzed. Results: An 11-gene panel (MT2A, UBE2S, CLTB, KRT7, IGFBP3, CTSH, NPC2, HMGA1, HNRNPAB, DTYMK, and IHNA) was established. DTPRGs were mainly correlated with nuclear division, chromosome segregation, and cell cycle pathways. Infiltration of immune cells was lower in the high-risk group while the inflammation-promoting and MCH-class I response pathway had higher activity in the high-risk group. A nomogram was generated with prognostic accuracy, further validated using clinical outcomes following therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Discussion: A prognostic model of lung adenocarcinoma based on DTPRGs was constructed. Targeting DTP cells is a potential therapeutic approach to prevent a drug tolerant state.

The Tibetan Plateau (TP) is often referred to as the “Asian Water Tower”, as it plays a crucial role in supplying water for ∼1.9 billion people. Lakes in this arid mountain region have a wide salinity gradient and are sensitive to the complex interactions between climate and the water cycle, affecting aquatic ecosystems and species distributions. Here, we analyzed relationships between measured environmental variables and the spatial distribution of surface sediment diatom assemblages from 45 lakes located throughout the TP with the intention of developing a diatom-inference model for salinity. Diatom assemblage composition and diversity differed among lakes from the western (W), southern (S), northern (N), and southeastern (E) regions of the TP. The most common taxa observed in the lake set, Pantocsekiella ocellata, Nitzschia palea, and Staurosira venter, tended to have widespread distributions across the TP. In general, diatom diversity and richness tended to be highest in lakes with salinity concentrations between 0.1 and 10 g/L and were lowest in high salinity lakes (>20 g/L) of the N region. Canonical correspondence analysis (CCA) identified lake water salinity and maximum lake depth as explaining a statistically significant portion of diatom assemblage variation. Weighted-averaging (WA) was used to develop a diatom-based salinity inference model (R2jack = 0.71, RMSEPjack = 0.28) based on diatom optima from freshwater to meso-hyposaline lakes of the TP. Diatom-salinity reconstructions and changes in diatom community composition can potentially be used to track long-term patterns in climate and environmental conditions across the highly complex mountain landscape of the TP.

Cyclic GMP-AMP synthetase (cGAS), recognized as the primary DNA sensor within cells, possesses the capability to identify foreign DNA molecules along with free DNA fragments. This identification process facilitates the production of type I IFNs through the activator of the interferon gene (STING) which induces the phosphorylation of downstream transcription factors. This action characterizes the most archetypal biological functionality of the cGAS-STING pathway. When treated with anti-tumor agents, cells experience DNA damage that triggers activation of the cGAS-STING pathway, culminating in the expression of type I IFNs and associated downstream interferon-stimulated genes. cGAS-STING is one of the important innate immune pathways,the role of type I IFNs in the articulation between innate immunity and T-cell antitumour immunity.type I IFNs promote the recruitment and activation of inflammatory cells (including NK cells) at the tumor site.Type I IFNs also can promote the activation and maturation of dendritic cel(DC), improve the antigen presentation of CD4+T lymphocytes, and enhance the cross-presentation of CD8+T lymphocytes to upregulating anti-tumor responses. This review discussed the cGAS-STING signaling and its mechanism and biological function in traditional tumor therapy and immunotherapy.

Introduction Obesity is a complex and multifactorial disease that has affected many adolescents in recent decades. Clinical practice guidelines recommend exercise as the key treatment option for adolescents with overweight and obesity. However, the effects of virtual reality (VR) exercise on the physical and brain health of adolescents with overweight and obese remain unclear. This study aims to evaluate the effects of physical and VR exercises on physical and brain outcomes and explore the differences in benefits between them. Moreover, we will apply a multiomics analysis to investigate the mechanism underlying the effects of physical and VR exercises on adolescents with overweight and obesity.Methods and analysis This randomised controlled clinical trial will include 220 adolescents with overweight and obesity aged between 11 and 17 years. The participants will be randomised into five groups after screening. Participants in the exercise groups will perform an exercise programme by adding physical or VR table tennis or soccer classes to routine physical education classes in schools three times a week for 8 weeks. Participants in the control group will maintain their usual physical activity. The primary outcome will be the change in body fat mass measured using bioelectrical impedance analysis. The secondary outcomes will include changes in other physical health-related parameters, brain health-related parameters and multiomics variables.Ethics and dissemination This study was approved by the Ethics Committee of Shanghai Sixth People’s Hospital and registered in the Chinese Clinical Trial Registry. Dissemination of the findings will include peer-reviewed publications, conference presentations and media releases.Trial registration number ChiCTR2300068786.

Modern pollen distribution and its relationship to vegetation and climate in the lower Yarlung Zangbo River are investigated to provide a reference for paleoenvironmental reconstructions and to improve the understanding of pollen dispersal patterns in mountainous regions. Twenty-eight modern samples collected in moss polsters from 800 and 5400 m a.s.l. are used for palynological analysis. Our results indicate that palynological assemblages and indicator species from moss polsters can reflect the vertical distribution of vegetation belts. Abies, Picea and Pinus pollen from the upper forests and shrub meadow elements (Ericaceae, Cyperaceae and Polygonum) show strong abilities to be transported upward, whereas pollen (e.g. Macaranga, Alnus and Rutaceae) and spore (e.g. Athyrium, Cyatheaceae, Dicranopteris, Pteris) taxa from the lower evergreen forests show weak abilities to be transported upward. An unusual finding is that Tsuga pollen from the lower coniferous forest tends to be transported downslope, probably due to the intense spring rainfall and associated surface runoff in the study area. Due to its potential impact on the geographic range shifts of plants, pollen dispersal may be an additional factor to be considered in studies of vegetation change in the southeastern Tibetan Plateau, such as the projection of Abies or Picea treeline under climate warming. Furthermore, the redundancy analysis shows that precipitation and wind speed are the main factors influencing pollen distribution in the study area.

Accurate lake depth mapping and estimation of changes in water level and water storage are fundamental significance for understanding the lake water resources on the Tibetan Plateau. In this study, combined with satellite images and bathymetric data, we comprehensively evaluate the accuracy of a multi-factor combined linear regression model (MLR) and machine learning models, create a depth distribution map and compare it with the spatial interpolation, and estimate the change of water level and water storage based on the inverted depth. The results indicated that the precision of the random forest (RF) was the highest with a coefficient of determination (R2) value (0.9311) and mean absolute error (MAE) values (1.13 m) in the test dataset and had high reliability in the overall depth distribution. The water level increased by 9.36 m at a rate of 0.47 m/y, and the water storage increased by 1.811 km3 from 1998 to 2018 based on inversion depth. The water level change was consistent with that of the Shuttle Radar Topography Mission (SRTM) method. Our work shows that this method may be employed to study the water depth distribution and its changes by combining with bathymetric data and satellite imagery in shallow lakes.

Light penetration and overheating are major issues facing the application of photothermal therapy. Here, the authors develop a temperature responsive hydrogel optical waveguide for controlled delivery of light to deep tumours and demonstrate biocompatibility and temperature responsive phototherapy in vivo

Abstract Background Heat stress is a major abiotic stress affecting the growth and development of plants, including crop species. Plants have evolved various adaptive strategies to help them survive heat stress, including maintaining membrane stability, encoding heat shock proteins (HSPs) and ROS-scavenging enzymes, and inducing molecular chaperone signaling. Brassinosteroids (BRs) are phytohormones that regulate various aspects of plant development, which have been implicated also in plant responses to heat stress, and resistance to heat in Arabidopsis thaliana is enhanced by adding exogenous BR. Brassinazole resistant 1 (BZR1), a transcription factor and positive regulator of BR signal, controls plant growth and development by directly regulating downstream target genes. However, the molecular mechanism at the basis of BR-mediated heat stress response is poorly understood. Here, we report the identification of a new factor critical for BR-regulated heat stress tolerance. Results We identified ERF49 in a genetic screen for proteins required for BR-regulated gene expression. We found that ERF49 is the direct target gene of BZR1 and that overexpressing ERF49 enhanced sensitivity of transgenic plants to heat stress. The transcription levels of heat shock factor HSFA2, heat stress-inducible gene DREB2A, and three heat shock protein (HSP) were significantly reduced under heat stress in ERF49-overexpressed transgenic plants. Transcriptional activity analysis in protoplast revealed that BZR1 inhibits ERF49 expression by binding to the promoter of ERF49. Our genetic analysis showed that dominant gain-of-function brassinazole resistant 1-1D mutant (bzr1-1D) exhibited lower sensitivity to heat stress compared with wild-type. Expressing ERF49-SRDX (a dominant repressor reporter of ERF49) in bzr1-1D significantly decreased the sensitivity of ERF49-SRDX/bzr1-1D transgenic plants to heat stress compared to bzr1-1D. Conclusions Our data provide clear evidence that BR increases thermotolerance of plants by repressing the expression of ERF49 through BZR1, and this process is dependent on the expression of downstream heat stress-inducible genes. Taken together, our work reveals a novel molecular mechanism mediating plant response to high temperature stress.

Measurement(s) Relative lake volume Technology Type(s) Remote sensing image and DEM data Sample Characteristic - Environment endorheic lake Sample Characteristic - Location Tibetan Plateau