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Abstract The rice paddy-direct seeding system has been widely adopted due to its low cost and convenience, whereas its application is mainly constrained by low seedling vigor, cold sensitivity, eventually resulting in reduced grain yield. Here, we show vig1a and vig1b, two allelic mutants of OsbZIP01, that both demonstrate greatly enhanced seedling vigor and chilling tolerance but differ in final grain production. The vig1a phenotype can be obtained via simultaneous mutation of the genes OsbZIP01 and OsbZIP18, or by selectively manipulating the basic region of OsbZIP01. Destroying the leucine zipper region of OsbZIP01 in vig1a turns vig1a to be vig1b. Further analysis reveals that OsbZIP01 and OsbZIP18 function cooperatively in diverse crucial biological programs that determine seedling establishment, chilling tolerance, and grain yield through their interactions. These findings provide a strategy toward simultaneously improving seedling vigor, chilling tolerance, and grain yield for rice production.

Abstract This paper provides a comprehensive and comparative analysis of extreme precipitation patterns from 1971 to 2015 in Nepal, a data scarce, but “hot spot” region in global climate change. We compare in‐situ observations and gridded precipitation data from the Asian Precipitation Highly Resolved Observational Data Integration Toward Evaluation of Water Resources (APHRODITE). Using 11 precipitation indices, we show that high‐intensity (RX1day, R95pTOT, R99pTOT) and frequency‐related indices (R10 mm, R20 mm) have decreased but annual maximum consecutive dry and wet days have increased. Observations affirm these trends found by the APHRODITE, but show smaller magnitudes likely due to differences in measurements at locations made below the 3,000 m elevation line. Spatially, the relatively dry western region has become wetter, and the relatively wet eastern region has become drier post‐2003. The weakening of the South Asia Monsoon circulation, particularly assessed by the Webster and Yang Monsoon Index, correlates strongly with extreme precipitation indices. Changes in upper‐level jet and associated lower‐level monsoon trough are identified as critical factors influencing the extreme precipitation trend post‐2003. This study is the first to confirm the efficacy of APHRODITE in providing spatial and temporal precipitation patterns in a data‐limited region. We conclude that monsoon weakened circulations and changes in regional wind fields play dominant roles in the long‐term temporal and spatial trends of extreme precipitation in Nepal. The reduced precipitation extremes in the wet eastern region may somewhat lessen severe flooding and erosion, but the drier western region may face heightened risks in precipitation‐related hazards in Nepal.

Avian influenza is a global zoonotic disease influencing bird conservation and public health. Climate and land-cover changes can significantly impact influenza-susceptible species' distribution, thereby influencing avian influenza outbreaks. The Qinghai-Tibetan Plateau (QTP) plays a crucial role in avian influenza virus transmission and is susceptible to environmental changes. Here, we focused on two influenza-susceptible birds, the bar-headed goose (Anser indicus) and brown-headed gull (Chroicocephalus brunnicephalus), to predict their distribution on the QTP under climate and land-cover change scenarios. We integrated satellite tracking, field surveys, and publicly available datasets to collect species occurrence. Then, we utilized Biomod models to predict bird distribution under current and future scenarios. Our results indicated that the distance to water bodies (DW) and the mean temperature of the wettest quarter (BIO 8) significantly influenced the distribution of bar-headed geese and brown-headed gulls. The highly suitable distributions of both species are concentrated in the northeastern QTP and the Changtang Plateau, with only the Qaidam Basin showing a decrease in the future. Their future distribution has roughly doubled, with expansions toward western and higher elevations. We highlighted the influence of climate and land cover changes on bird distribution, and identified key areas of bird distribution, which are also critical areas for future avian influenza monitoring and prevention.

The increasing industrial development and energy demand have necessitated the maximization of available energy use and the deployment of renewable resources. Effective energy management, optimal modeling, and efficient planning are essential to transform the power system into a high-efficiency, optimal model. This study focuses on the initial step of modeling smart buildings (SBs) equipped with non-responsive devices and renewable photovoltaic sources. A comprehensive energy management (EM) plan is formulated for these buildings, incorporating the KNX protocol for solar energy system management. Batteries are integrated into the building model to store energy during periods of low consumption and serve as generators during peak load conditions, with the primary goal of minimizing power system losses and related costs. To address the complexity of this model, whale optimization algorithm (WOA) is employed for optimization. Optimal candidate buses are selected for interconnected building management based on a suggested sensitivity analysis to minimize losses. Cost performance is then assessed, considering energy production and sales. The findings indicate that substantial control of operating costs can be achieved through strategic management of battery charging and discharging, as well as the utilization of photovoltaic units. The proposed model is evaluated across various scenarios using a test system comprising 30 modified system, demonstrating its effectiveness in enhancing energy efficiency and management.

Abstract The inadequate tumor accumulation of anti-cancer agents is a major shortcoming of current therapeutic drugs and remains an even more significant concern in the clinical prospects for nanomedicines. Various strategies aiming at regulating the intratumoral permeability of therapeutic drugs have been explored in preclinical studies, with a primary focus on vascular regulation and stromal reduction. However, these methods may trigger or facilitate tumor metastasis as a tradeoff. Therefore, there is an urgent need for innovative strategies that boost intratumoral drug accumulation without compromising treatment outcomes. As another important factor affecting drug tumor accumulation besides vasculature and stroma, the impact of tumor-associated lymphatic vessels (LVs) has not been widely considered. In the current research, we verified that anlotinib, a tyrosine kinase inhibitor with anti-lymphangiogenesis activity, and SAR131675, a selective VEGFR-3 inhibitor, effectively decreased the density of tumor lymphatic vessels in mouse cancer models, further enhancing drug accumulation in tumor tissue. By combining anlotinib with therapeutic drugs, including doxorubicin (Dox), liposomal doxorubicin (Lip-Dox), and anti-PD-L1 antibody, we observed improved anti-tumor efficacy in comparison with monotherapy regimens. Meanwhile, this strategy significantly reduced tumor metastasis and elicited stronger anti-tumor immune responses. Our work describes a new, clinically transferrable approach to augmenting intratumoral drug accumulation, which shows great potential to address the current, unsatisfactory efficacies of therapeutic drugs without introducing metastatic risk.

Abstract This study examined the impact of COVID-19 on 28 indicators of match technical performance (MTP) for football attacking players upon their return to play. Analyzing data from 100 players in the Big Five European football leagues, covering 1500 matches each before and after COVID-19 over 3 years (2020–2023), revealed significant differences in 76% of players’ MTP indicators. Notably, 14 indicators, particularly the five indicators linked to scoring, significantly decreased post-COVID-19. On average, players needed 3.09 matches to regain pre-infection MTP levels. The impact varied across player groups, with those in the elite group showing a milder effect; they required an average of 2.64 matches for recovery, compared to the control group’s 3.55 matches. We found that, with increasing age, the majority of players’ MTP indicators did not exhibit significant changes, both before and after they contracted COVID-19. In conclusion, the study highlighted the negative impact of COVID-19 on football attacking players’ MTP. Players in the elite group experienced fewer adverse effects than those in the control group. This insight assisted coaches and managers in evaluating the impact of COVID-19 and similar virus-induced illnesses on players’ MTP, enabling them to formulate training regimens for recovery and specific match tactics upon players' return to play.

Extrinsic and endocrine factors are important mechanisms influencing the timing of spring bird migration. Whooper swans (Cygnus cygnus), including 122 adults and subadults over one year old and 98 juveniles under one year old, were satellite tracked to obtain detailed locational data at a wintering ground from 2015 to 2020. We assessed the effects of temperature, wind, photoperiod, available food resources, and sex hormones on age-related timing of spring migration. Our results suggested that both photoperiod and temperature had the greatest impacts on the timing of spring migration of adults, subadults and juveniles when food resources and wind conditions were favourable. With increasing photoperiod and temperature, the peak sex hormone concentrations of adults and subadults occurred one month earlier than that of juveniles, which corresponded to the peak of their departure time. Our study showed the synergistic impact of photoperiod and temperature and their variation among adults, subadults and juveniles on the initiation of spring migration. Compared with juveniles, adults and subadults with spring migration experience and reproductive needs could adjust their behaviours more quickly before departure based on changes in environmental conditions.

Abstract Aqueous zinc-ion batteries (AZIBs) are promising for future large-scale energy storage systems, however, suffer from inferior cycling life due to the dendrites growth and side reaction on Zn metal anode. Herein, a fast ion conductor Na5YSi4O12 (NYSO) was synthesized and fabricated as a protection layer of the Zn metal anode. By adjusting the thickness, an optimized NYSO coating of 20.3 µm was obtained and the corresponding symmetry cell demonstrates an extended life span of 1896 h at the current density of 0.5 mA cm−2. In addition, a favorable rate performance of the NYSO@Zn anode at a high current density of 10 mA cm−2 was achieved. Benefiting from the NYSO coating, uniform diffusion and deposition of Zn2+ on the Zn anode could be realized, leading to the elimination of Zn dendrites and side reactions. Therefore, the aqueous NYSO@Zn|CNT@MnO2 full cell shows superior capacity and cycling stability to that of the bare Zn full cell.

Abstract Exploiting solid electrolyte (SE) materials with high ionic conductivity, good interfacial compatibility, and conformal contact with electrodes is essential for solid-state sodium metal batteries (SSBs). Here we report a crystalline Na5SmSi4O12 SE which features high room-temperature ionic conductivity of 2.9 × 10−3 S cm−1 and a low activation energy of 0.15 eV. All-solid-state symmetric cell with Na5SmSi4O12 delivers excellent cycling life over 800 h at 0.15 mA h cm−2 and a high critical current density of 1.4 mA cm−2. Such excellent electrochemical performance is attributed to an electrochemically induced in-situ crystalline-to-amorphous (CTA) transformation propagating from the interface to the bulk during repeated deposition and stripping of sodium, which leads to faster ionic transport and superior interfacial properties. Impressively, the Na|Na5SmSi4O12|Na3V2(PO4)3 sodium metal batteries achieve a remarkable cycling performance over 4000 cycles (6 months) with no capacity loss. These results not only identify Na5SmSi4O12 as a promising SE but also emphasize the potential of the CTA transition as a promising mechanism towards long-lasting SSBs.

Abstract ‘Urban Dry (Wet) Islands’ (UDI/UWI) represents microclimate change that impacts ecosystems and human well-being. However, causes of the UDI (UWI) phenomena are not fully understood due to the lack of empirical data. Here, we quantify UDI (UWI) using global observations of atmospheric humidity, evapotranspiration (ET), and land surface characteristics across 25 large urban agglomerations. We show that UDI (17) and UWI (8) are closely tied to local ET, global warming, and ‘Urban Heat Islands’ through intertwined linkages with water and energy balances. UDI is most pronounced in humid vegetated regions where mean urban-rural annual ET differences are as high as 215 mm, whereas UWI is found in arid regions or in climates with dry summers. We conclude that ET can be used as a single variable to explain emerging urban environmental changes. Our study supports a concerted strategy of restoring nature’s ET power as effective ‘Nature-based Solutions’ to mitigate the negative environmental effects of urbanization.

Abstract The Kunming‐Montreal Global Biodiversity Framework requires effective actions to bend the curve of biodiversity loss by 2030. Wildlife trade, a direct drive of biodiversity decline, calls for more effective regulations to both protect wildlife populations in the wild and facilitate sustainable use of wildlife resources to meet human needs. This call has become particularly urgent in light of the COVID‐19 pandemic. In 2021, China's List of State Key Protected Wild Animals, a list of fauna under the strictest protection by national legislation, has been updated in the year 2021, 32 years after its first release, increasing its coverage (from the original 13%) an 11% of species across taxa. Combined with the updated List of State Protected Terrestrial Wild Animals which covers species with lower protection priority, these two national lists already cover 77% terrestrial vertebrate species of China. Such a blacklist approach, placing threatened species under a list of legal protection, is a common practice globally in species conservation. We discussed pros and cons of this dominant strategy and further explored the potential integration with a whitelist approach, listing all wildlife and only permitting regulated uses of certain species. We propose a mixed approach combining black and whitelists at different administration levels which could perhaps be first adopted in China. This is mainly due to the fact that in addition to illegal harvesting from the wild, traded wildlife in China are mostly from captive breeding and related laundering of wild‐caught animals.

Abstract The manipulation of water resources is a common human solution to water-related problems. Of particular interest because of impacts on both source and destination is the anthropogenic movement of water from one basin to another, or inter-basin transfers (IBTs). In the United States, IBTs occur widely in both wet and dry regions, but IBT data are not collated and served in a coordinated way. Thus researchers wishing to account for transfers between basins have faced difficulty in doing so. Here we present the outcome of a systematic investigation into inter-basin surface water transfers connected with public water supplies in the conterminous United States (CONUS), 1986 to 2015. The present open-access geodatabase includes transfer volumes collected, evaluated, and compiled from disparate sources. We provide an updated snapshot of CONUS IBTs at a higher spatial resolution of points of withdrawal and delivery than previous datasets. This paper puts the national inter-basin transfer data in context, and shows how we acquired, structured, and validated the locations and volumes of surface water transfers in public water systems.

The aim of this study was to establish a new method for the determination of homoisoflavanones (Ⅲ, Ⅳ, V) in polygonatum odoratum(POD) by combination of thin layer chromatography (TLC) and chemical derivative resonance Raman spectroscopy (RRS). The twice chromatography method of TLC was used to improve the specificity of the component to be tested; the method of the relative Rf was used to reduce the use of the reference substance of the component to be tested; the chemical derivatization method was used to improve the signal intensity of Raman spectrum for the component to be tested in POD, so as to obtain a trace amount fingerprint structure information of the measured component. The method exhibits robust specificity, high sensitivity, and reliable stability, there by offering a novel reference approach for the identification and evaluation of homoisoflavanones (Ⅲ, Ⅳ, V) in POD.

Abstract Hepatocellular carcinoma (HCC) is a common solid tumor with high rate of recurrence and mortality. Anti-angiogenesis drugs have been used for the therapy of HCC. However, anti-angiogenic drug resistance commonly occurs during HCC treatment. Thus, identification of a novel VEGFA regulator would be better understanding for HCC progression and anti-angiogenic therapy resistance. Ubiquitin specific protease 22 (USP22) as a deubiquitinating enzyme, participates in a variety of biological processes in numerous tumors. While the molecular mechanism underlying the effects of USP22 on angiogenesis is still needed to be clarified. Here, our results demonstrated that USP22 acts as a co-activator of VEGFA transcription. Importantly, USP22 is involved in maintenance of ZEB1 stability via its deubiquitinase activity. USP22 was recruited to ZEB1-binding elements on the promoter of VEGFA, thereby altering histone H2Bub levels, to enhance ZEB1-mediated VEGFA transcription. USP22 depletion decreased cell proliferation, migration, Vascular Mimicry (VM) formation, and angiogenesis. Furthermore, we provided the evidence to show that knockdown of USP22 inhibited HCC growth in tumor-bearing nude mice. In addition, the expression of USP22 is positively correlated with that of ZEB1 in clinical HCC samples. Our findings suggest that USP22 participates in the promotion of HCC progression, if not all, at least partially via up-regulation of VEGFA transcription, providing a novel therapeutic target for anti-angiogenic drug resistance in HCC.

Graphite nitrogen, pyridine nitrogen and pyrrole nitrogen are the main nitrogen types in nitrogen-doped graphene materials. In order to investigate the mechanism of the oxygen reduction activity of nitrogen-doped graphene, several models of nitrogen-doped graphene with different nitrogen contents and different nitrogen types are developed. The nitrogen content is varied from 1.3 at% to 7.8 at%, and the adsorption energy is calculated according to the established models, then the band gaps are analyzed through the optimization results, so as to compare the magnitude of the conductivity. Finally, the oxygen reduction activity of graphite nitrogen-doped graphene (GNG) is found to be better than pyridine nitrogen-doped graphene (PDNG) and pyrrole nitrogen-doped graphene (PLNG) when the nitrogen content is lower than 2.6 at%, and the oxygen reduction activity of PDNG is the best when the nitrogen content was higher than 2.6 at%.

BackgroundArtificial forest can have great potential in serving as habitat to wildlife, depending on different management methods. As the state-owned forest farms now play a new role in ecological conservation in China, the biological richness of this kind of land-use type is understudied. Once owned by a mining company, a largest state-owned forest farm, Jingxi Forest Farm, has been reformed to be a state-owned forest farm with the purpose of conservation since 2017. Although this 116.4 km2 forest farm holds a near-healthy montaine ecosystem very representative in North China, a large proportion of artificial coniferous forest in the forest farm has been proven to hold less biodiversity than natural vegetation. This situation, however, provides a great opportunity for ecological restoration and biodiversity conservation. Therefore, from November 2019 to December 2020, we conducted a set of biodiversity surveys, whose results will serve as a baseline for further restoration and conservation.New informationHere, we report the result of a multi-taxa fauna diversity survey conducted in Jingxi Forest Farm mainly in year 2020 with explicit spatial information. It is the first survey of its kind conducted in this area, revealing a total of 19 species of mammals, 86 birds, four reptiles, two amphibians and one fish species, as well as 101 species of insects. Four species of mammals are identified as data-poor species as they have less than 100 occurrence records with coordination in the GBIF database. One species of insect, representing one new provincial record genus of Beijing, is reported.

Abstract Background The safe distance between the intraoperative resection line and the visible margin of the distal rectal tumor after preoperative radiotherapy is unclear. We aimed to investigate the furthest tumor intramural spread distance in fresh tissue to determine a safe distal intraoperative resection margin length. Methods Twenty rectal cancer specimens were collected after preoperative radiotherapy. Tumor intramural spread distances were defined as the distance between the tumor’s visible and microscopic margins. Visible tumor margins in fresh specimens were identified during the operation and were labeled with 5 - 0 sutures under the naked eye at the distal 5, 6, and 7 o’clock directions of visible margins immediately after removal of the tumor. After fixation with formalin, the sutures were injected with nanocarbon particles. Longitudinal tissues were collected along three labels and stained with hematoxylin and eosin. The spread distance after formalin fixation was measured between the furthest intramural spread of tumor cells and the nanocarbon under a microscope. A positive intramural spread distance indicated that the furthest tumor cell was distal to the nanocarbon, and a negative value indicated that the tumor cell was proximal to the nanocarbon. The tumor intramural spread distance in fresh tissue during the operation was 1.75 times the tumor intramural spread distance after formalin fixation according to the literature. Results At the distal 5, 6, and 7 o’clock direction, seven (35%), five (25%), and six (30%) patients, respectively, had distal tumor cell intramural spread distance > 0 mm. The mean and 95% confidence interval of tumor cell intramural spread distance in fresh tissue during operation was − 0.3 (95%CI − 4.0 ~ 3.4) mm, − 0.9 (95%CI − 3.4 ~ 1.7) mm, and − 0.4 (95%CI − 3.5 ~ 2.8) mm, respectively. The maximal intraoperative intramural spread distances in fresh tissue were 8.8, 7, and 7 mm, respectively. Conclusions The intraoperative distance between the distal resection line and the visible margin of the rectal tumor after radiotherapy should not be less than 1 cm to ensure oncological safety.

Urbanization is known to elevate storm runoff, but how it influences carbon cycle and ecosystem productivity through altering the evapotranspiration (ET) process is less clear. We examined the combined effects of urbanization including change in impervious surface area (ISA) and climate variability on the water and carbon balances of the Qinhuai River Basin (QRB) over 2001–2018. QRB represents a typical rice paddy-dominated region that experienced rapid urbanization in southern China. We improved a monthly scale water supply stress index ecosystem service model by integrating local eddy flux measurements and high-resolution remote sensing data. We found a significant downward trend in both ET (−4.6 mm yr ^−1 , p < 0.05) and gross primary productivity (GPP) (−10.4 gC m ^−2 yr ^−1 , p < 0.05) but a significant upward trend in water yield ( Q ) (+28.6 mm yr ^−1 , p < 0.05). These ecosystem function changes coincided with a 96% increase in urban areas, 1.9-fold increase in ISA, and a 37% reduction in rice paddy fields. The mean annual watershed GPP decreased from 1048 gC m ^−2 to 998 gC m ^−2 while the annual Q increased from 284 mm to 669 mm from 2001 to 2018. Scenario modeling experiments suggested that the negative impacts of loss of rice paddy fields and increase in ISA on ET and GPP overwhelmed the positive impacts of climate warming. The reduction in GPP and increase in Q were largely attributed to the increases in ISA, not necessarily due to changes in land use types (e.g. urban area). The expansion of urban area, increase in ISA and reduction in leaf area index, and increase in precipitation explained the increase in Q . Our research offers insight about the interactions of carbon and water cycles through the critical ET processes under a changing climate and land surface characteristics at a watershed level. Our modeling tool and analysis provides land managers and policy makers information for designing effective ‘Urban Nature-based Solutions’ to mitigate the negative environmental effects of urbanization on carbon and water resources.

Abstract Androgen receptor (AR) signaling drives prostate cancer (PC) progression. Androgen deprivation therapy (ADT) is temporally effective, whereas drug resistance inevitably develops. Abnormal expression of AR/ARV7 (the most common AR splicing variant) is critical for endocrine resistance, while the detailed mechanism is still elusive. In this study, bioinformatics and immunohistochemical analyses demonstrate that RNF8 is high expressed in PC and castration-resistant PC (CRPC) samples and the expression of RNF8 is positively correlated with the Gleason score. The high expression of RNF8 in PCs predicts a poor prognosis. These results provide a potential function of RNF8 in PC progression. Furthermore, the mRNA expression of RNF8 is positively correlated with that of AR in PC. Mechanistically, we find that RNF8 upregulates c-Myc-induced AR transcription via altering histone modifications at the c-Myc binding site within the AR gene. RNF8 also acts as a co-activator of AR, promoting the recruitment of AR/ARV7 to the KLK3 (PSA) promoter, where RNF8 modulates histone modifications. These functions of RNF8 are dependent on its E3 ligase activity. RNF8 knockdown further reduces AR transactivation and PSA expression in CRPC cells with enzalutamide treatment. RNF8 depletion restrains cell proliferation and alleviates enzalutamide resistance in CRPC cells. Our findings indicate that RNF8 may be a potential therapeutic target for endocrine resistance in PC.

Abstract Background To investigate the learning curve of conformal sphincter preservation operation (CSPO) in the treatment of ultralow rectal cancer and to further explore the influencing factors of operation time. Methods From August 2011 to April 2020, 108 consecutive patients with ultralow rectal cancer underwent CSPO by the same surgeon in the Department of Colorectal Surgery of Changhai Hospital. The moving average and cumulative sum control chart (CUSUM) curve were used to analyze the learning curve. The preoperative clinical baseline data, postoperative pathological data, postoperative complications, and survival data were compared before and after the completion of learning curve. The influencing factors of CSPO operation time were analyzed by univariate and multivariate analysis. Results According to the results of moving average and CUSUM method, CSPO learning curve was divided into learning period (1–45 cases) and learning completion period (46–108 cases). There was no significant difference in preoperative clinical baseline data, postoperative pathological data, postoperative complications, and survival data between the two stages. Compared with the learning period, the operation time (P < 0.05), blood loss (P < 0.05), postoperative flatus and defecation time (P < 0.05), liquid diet time (P < 0.05), and postoperative hospital stay (P < 0.05) in the learning completion period were significantly reduced, and the difference was statistically significant. Univariate and multivariate analysis showed that distance of tumor from anal verge (≥ 4cm vs. < 4cm, P = 0.039) and T stage (T3 vs. T1-2, P = 0.022) was independent risk factors for prolonging the operation time of CSPO. Conclusions For surgeons with laparoscopic surgery experience, about 45 cases of CSPO are needed to cross the learning curve. At the initial stage of CSPO, beginners are recommended to select patients with ultralow rectal cancer whose distance of tumor from anal verge is less than 4 cm and tumor stage is less than T3 for practice, which can enable beginners to reduce the operation time, accumulate experience, build self-confidence, and shorten the learning curve on the premise of safety.

Objective To establish scrap indicators for key equipment in blood screening laboratory of blood centers and quantitatively assess the running status of key equipment, so as to provide a scientific method for equipment scrap. Methods Through the literature review and Delphi method, the scrap indicators of key equipment in blood screening laboratories were established in terms of applicability, economy and advancement of the equipment. The weights of relevant indicators were calculated by analysis hierarchy process (AHP), and the quantitative assessment model of equipment scrap priority was established according to the indicators and its weight. The equipment running data from January 2020 to December 2020 of Laboratory Department were collected and analyzed using the model, and its accuracy was verified based on experience. Results Thirteen second-level scrap indicators were established, and the weights of the three first-level indexes of applicability, economy and advancement were 0.582, 0.114 and 0.306, respectively. Among the total 30 key equipment, the model score of 4 equipment was less than 0.5, and the running status after manually checking met the scrap standard. Conclusion The model can accurately assess the scrap priority of key equipment and facilitate the procurement budget and scrapping identification in advance, which can avoid the waste of resources and ensure safe, efficient and orderly laboratory work.

Legged robots can have a unique role in manipulating objects in dynamic, human-centric, or otherwise inaccessible environments. Although most legged robotics research to date typically focuses on traversing these challenging environments, many legged platform demonstrations have also included “moving an object” as a way of doing tangible work. Legged robots can be designed to manipulate a particular type of object (e.g., a cardboard box, a soccer ball, or a larger piece of furniture), by themselves or collaboratively. The objective of this review is to collect and learn from these examples, to both organize the work done so far in the community and highlight interesting open avenues for future work. This review categorizes existing works into four main manipulation methods: object interactions without grasping, manipulation with walking legs, dedicated non-locomotive arms, and legged teams. Each method has different design and autonomy features, which are illustrated by available examples in the literature. Based on a few simplifying assumptions, we further provide quantitative comparisons for the range of possible relative sizes of the manipulated object with respect to the robot. Taken together, these examples suggest new directions for research in legged robot manipulation, such as multifunctional limbs, terrain modeling, or learning-based control, to support a number of new deployments in challenging indoor/outdoor scenarios in warehouses/construction sites, preserved natural areas, and especially for home robotics.

Extracellular vesicles (EVs) are nano-sized membrane vesicles released by various cell types. Mammalian EVs have been studied in-depth, but the role of plant EVs has rarely been explored. For the first time, EVs from Drynariae Rhizoma roots were isolated and identified using transmission electron microscopy and a flow nano analyzer. Proteomics and bioinformatics were applied to determine the protein composition and complete the functional analysis of the EVs. Seventy-seven proteins were identified from Drynariae Rhizoma root-derived EVs, with enzymes accounting for 47% of the proteins. All of the enzymes were involved in important biological processes in plants. Most of them, including NAD(P)H-quinone oxidoreductase, were enriched in the oxidative phosphorylation pathway in plants and humans, and Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease, which are associated with oxidative stress in humans. These findings suggested that EVs from Drynariae Rhizoma roots could alleviate such neurological diseases and that enzymes, especially NAD(P)H-quinone oxidoreductase, might play an important role in the process.

Abstract Hepatocellular carcinoma (HCC) is the most common visceral neoplasms with its heterogeneity and high rate of recurrence. HCC is characterized to be delayed diagnosis and the development of resistant disease. However, the molecular mechanism for HCC pathogenesis and progression remains largely unknown. Here, we demonstrated that ubiquitin-specific protease14 (USP14) is highly expressed in HCC samples, and the higher expression of USP14 is positively correlated with poor prognosis. Interestingly, USP14 is involved in the maintenance of HIF1-α stability to activate HIF1-α-induced transactivation via its deubiquitinase activity. USP14 depletion or its specific inhibitor IU1 treatment decreased cell proliferation, invasion, migration, and Vascular Mimicry (VM) formation even under hypoxia conditions in HCC cell lines. Moreover, we provided the evidence to show that knockdown of USP14 or USP14 inhibitor (IU1) treatment inhibited tumor growth in tumor-bearing nude mice. Our findings suggest that USP14 maintains HIF1-α stability through its deubiquitination activity, providing a potential biomarker for the early diagnosis and therapy of HCC.

Pre-eclampsia (PE) is a type of hypertensive disorder during pregnancy, which is a serious threat to the life of mother and fetus. It is a placenta-derived disease that results in placental damage and necrosis due to systemic small vessel spasms that cause pathological changes such as ischemia and hypoxia and oxidative stress, which leads to fetal and maternal damage. In this study, four types of risk factors, namely, clinical epidemiology, hemodynamics, basic biochemistry, and biomarkers, were used for the initial selection of model parameters related to PE, and factors that were easily available and clinically recognized as being associated with a higher risk of PE were selected based on hospital medical record data. The model parameters were then further analyzed and screened in two subgroups: early-onset pre-eclampsia (EOPE) and late-onset pre-eclampsia (LOPE). Dynamic gestational week prediction model for PE using decision tree ID3 algorithm in machine learning. Performance of the model was: macro average (precision = 76%, recall = 73%, F1-score = 75%), weighted average (precision = 88%, recall = 89%, F1-score = 89%) and overall accuracy is 86%. In this study, the addition of the dynamic timeline parameter “gestational week” made the model more convenient for clinical application and achieved effective PE subgroup prediction.

BackgroundHypertensive disorders in pregnancy (HDP) are diseases that coexist with pregnancy and hypertension. The pathogenesis of this disease is complex, and different physiological and pathological states can develop different subtypes of HDP.ObjectiveTo investigate the predictive effects of different variable selection and modeling methods on four HDP subtypes: gestational hypertension, early-onset preeclampsia, late-onset preeclampsia, and chronic hypertension complicated with preeclampsia.MethodsThis research was a retrospective study of pregnant women who attended antenatal care and labored at Beijing Maternity Hospital, Beijing Haidian District Maternal and Child Health Hospital, and Peking University People's Hospital. We extracted maternal demographic data and clinical characteristics for risk factor analysis and included gestational week as a parameter in this study. Finally, we developed a dynamic prediction model for HDP subtypes by nonlinear regression, support vector machine, stepwise regression, and Lasso regression methods.ResultsThe AUCs of the Lasso regression dynamic prediction model for each subtype were 0.910, 0.962, 0.859, and 0.955, respectively. The AUC of the Lasso regression dynamic prediction model was higher than those of the other three prediction models. The accuracy of the Lasso regression dynamic prediction model was above 85%, and the highest was close to 92%. For the four subgroups, the Lasso regression dynamic prediction model had the best comprehensive performance in clinical application. The placental growth factor was tested significant (P

The construction of the Three Gorges Dam Project had changed the forest landscapes and threatened the bird diversity of the Three Gorges Reservoir (TGR) area. For restoring degraded ecosystems and protecting biodiversity, the government has carried out a series of ecological projects in recent years, which has significantly restored the forest of the TGR area. However, the fragmentation of forest landscapes in the TGR area was not clearly improved by these ecological projects, and we were concerned that some birds might be impacted. Therefore, in this research, we studied the effects of forest amount and fragmentation on diversity of different bird guilds, to develop the effective strategies of forest restoration for bird preservation in the TGR area. We first selected a series of forest landscapes where forest amount and fragmentation were independent of each other to conduct bird surveys, and then used structural equation models to examine their direct and indirect effects on species richness and relative abundance of four bird guilds (vertical-profile generalists, understory birds, edge users and ground users). The results showed that forest amount had direct positive effects on diversity of all bird guilds, and fragmentation had indirect negative effects on diversity of vertical-profile generalists and understory birds that was mediated through vegetation condition. We believe that to increase forest amount in the landscapes undoubtedly plays an important role in bird conservation. Meanwhile, we also need to be alert to the threats that fragmentation may pose to birds by reducing forest quality. We suggest that optimizing landscape configuration and improving forest quality should both be emphasized while restoring the forest. For example, restoring the areas between forest patches preferentially to increase connectivity in the landscapes, and transforming the degraded mono-specific forests into mixed forests through replanting to optimize the stand structure.

Erlotinib is a highly specific and reversible epidermal growth factor receptor tyrosine kinase inhibitor for the targeted therapy of non-small-cell lung cancer (NSCLC) However, the efficacy of erlotinib is limited because the development of drug resistance during chemotherapy. Indoleamine 2,3-dioxygenase-1 (IDO1) is a rate-limiting tryptophan catabolic enzyme that is activated in many human cancers. In this study, we designed a series of erlotinib-based 1,2,3-triazole compounds by combining erlotinib with phenyl or benzyl azide. Attentive FP prediction model was used to predict the bioactivity of those compounds. We discovered that most of the erlotinib-based 1,2,3-triazole compounds are capable of suppressing IDO1 activities in vitro experiments. Among them, compound 14b (IC50 = 0.59 ± 0.05 μM) had the strongest inhibitory effect on IDO1. In addition, compound 14b significantly inhibited tumor growth comparable to the antitumor activity of erlotinib and the IDO1 inhibitor epacadostat in murine tumor models.

Abstract The COVID-19 pandemic poses a global threat to public health and economy. The continuously emerging SARS-CoV-2 variants present a major challenge to the development of antiviral agents and vaccines. In this study, we identified that EK1 and cholesterol-coupled derivative of EK1, EK1C4, as pan-CoV fusion inhibitors, exhibit potent antiviral activity against SARS-CoV-2 infection in both lung- and intestine-derived cell lines (Calu-3 and Caco2, respectively). They are also effective against infection of pseudotyped SARS-CoV-2 variants B.1.1.7 (Alpha) and B.1.1.248 (Gamma) as well as those with mutations in S protein, including N417T, E484K, N501Y, and D614G, which are common in South African and Brazilian variants. Crystal structure revealed that EK1 targets the HR1 domain in the SARS-CoV-2 S protein to block virus-cell fusion and provide mechanistic insights into its broad and effective antiviral activity. Nasal administration of EK1 peptides to hACE2 transgenic mice significantly reduced viral titers in lung and intestinal tissues. EK1 showed good safety profiles in various animal models, supporting further clinical development of EK1-based pan-CoV fusion inhibitors against SARS-CoV-2 and its variants.

According to statistics, lung cancer kills 1.8 million people each year and is the main cause of cancer mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for over 85% of all lung cancers. Lung cancer has a strong genetic predisposition, demonstrating that the susceptibility and survival of lung cancer are related to specific genes. Genome-wide association studies (GWASs) and next-generation sequencing have been used to discover genes related to NSCLC. However, many studies ignored the intricate interaction information between gene pairs. In the paper, we proposed a novel deep learning method named Deep-LC for predicting NSCLC-related genes. First, we built a gene interaction network and used graph convolutional networks (GCNs) to extract features of genes and interactions between gene pairs. Then a simple convolutional neural network (CNN) module is used as the decoder to decide whether the gene is related to the disease. Deep-LC is an end-to-end method, and from the evaluation results, we can conclude that Deep-LC performs well in mining potential NSCLC-related genes and performs better than existing state-of-the-art methods.

Indoleamine 2,3-dioxygenase 1 (IDO1) plays a predominant role in cancer immunotherapy which catalyzes the initial and rate limiting steps of the kynurenine pathway as a key enzyme. To explore novel IDO1 inhibitors, five derivatives of erlotinib-linked 1,2,3-triazole compounds were designed by using a structure-based drug design strategy. Drug-target interactions (DTI) were predicted by DeePurpose, an easy-to-use deep learning library that contains more than 50 algorithms. The DTI prediction results suggested that the designed molecules have potential inhibitory activities for IDO1. Chemical syntheses and bioassays showed that the compounds exhibited remarkable inhibitory activities against IDO1, among them, compound e was the most potent with an IC50 value of 0.32 ± 0.07 μM in the Hela cell assay. The docking model and ADME analysis exhibited that the effective interactions of these compounds with heme iron and better drug-likeness ensured the IDO1 inhibitory activities. The studies suggested that compound e was a novel and interesting IDO1 inhibitor for further development.

IntroductionChronic constipation can be treated by injecting botulinum toxin into the anal sphincter to decrease anal basal pressure. To assess the effect of botulinum toxin, we investigated the factors that contribute to changes in anal basal pressure after injection.MethodsThis was a retrospective study conducted in a tertiary hospital in the Netherlands. We included children with chronic constipation treated with botulinum toxin injections and measured anal basal pressure before and after each injection. Multivariable linear regression analyses were used.ResultsWe investigated 30 cases with idiopathic constipation. Their median age was 20.5 (7.75–53.25) months. Anal basal pressure decreased after injection in 20 cases. The mean decrease of anal basal pressure after injection was 18.17 ± 35.22 mmHg. The anal basal pressure change was linearly correlated with preinjection pressure (R2 = 0.593, P < 0.001). A significant decrease of pressure was observed in patients with preinjection pressure > 70 mmHg. Preinjection anal basal pressure (β = −0.913, P < 0.001) and rectal washouts (β = −21.015, P = 0.007) contributed significantly to pressure changes. Changes in anal basal pressure were also significantly associated with patients' weights (β = 0.512, 95% CI, 0.011–1.013) and sex (β = 22.971, 95% CI, 9.205–36.736).ConclusionsBotulinum toxin significantly decreases anal basal pressure when preinjection pressure is higher than 70 mmHg. In patients with severely elevated anal basal pressure, we recommend rectal washouts to promote the decrease of anal basal pressure.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are emerging at the vanguard of therapy for non-small-cell lung cancer (NSCLC) patients with EGFR-activating mutations. However, the increasing therapeutic resistance caused by novel mutations or activated bypass pathways has impaired their performance. In this study, we link one of the commercial EGFR-TKIs, Erlotinib, to different azide compounds to synthesize a novel class of 1,2,3-triazole ring-containing Erlotinib derivatives. We discovered that several new compounds show robust antiproliferation activity against diverse NSCLC cells in vitro including PC-9, H460, H1975 and A549. Two of the most potent compounds, e4 and e12 have been found to be more efficient than Erlotinib in all NSCLC cell lines except PC-9. They significantly induce apoptosis and cell cycle arrest in PC-9 and H460 cells. The antitumor efficacy of compound e4 in vivo is close to that of Erlotinib in a PC-9 xenograft mouse model. Most Erlotinib-1,2,3-triazole compounds exhibit moderate to good inhibitory activities toward wild-type EGFR as indicated by enzyme-linked immunosorbent assay (ELISA), and the EGFR phosphorylation was inhibited in H460 and PC-9 cells exposed to e4 or e12. These data suggest that these Erlotinib-1,2,3-triazole compounds are suitable candidates for use against NSCLC and more unknown mechanisms merit further investigation.

BackgroundImmunotherapy has emerged as a promising treatment for non-small cell lung cancer (NSCLC). Yet, some patients cannot benefit from immunotherapy, and reliable biomarkers for selecting sensitive patients are needed. Herein, we performed a meta-analysis to evaluate the predictive value of tumor mutational burden (TMB) in NSCLC patients treated with immunotherapy.MethodsEligible studies were comprehensively searched from electronic databases prior to August 31, 2021. Meta-analyses of high TMB versus low TMB as well as immunotherapy versus chemotherapy in patients with high/low TMB were conducted. Hazard ratio (HR) with corresponding 95% confidence interval (95%CI) for progression-free survival (PFS) and overall survival (OS) and odds ratio (OR) with 95%CI for objective response rate (ORR) were calculated.ResultsA total of 31 datasets (3437 patients) and 6 randomized controlled trials (3662 patients) were available for meta-analyses of high TMB versus low TMB and immunotherapy versus chemotherapy, respectively. High TMB predicted significantly favorable PFS (HR = 0.54, 95%CI: 0.46-0.63, PConclusionThis meta-analysis demonstrates more clinical benefits concerning treatment response and survival outcomes in high-TMB NSCLC patients who are treated with immunotherapy. TMB is a promising biomarker for discriminating NSCLC patients who can benefit more from immunotherapy.

Cervical cancer is one of the most important cause of cancer-related death and presents a major public health problem in many countries. To search for more novel antitumor agents against cervical cancer, 14 erlotinib-linked 1,2,3-triazole compounds were designed, synthesized, and evaluated for their anti-tumor activity. The compounds were confirmed by 1H NMR, 13C NMR, and high-resolution mass spectra (HR MS). Antitumor activity assay results indicated that six of those compounds have remarkable inhibitory activity against human cervical cancer HeLa cells in vitro, among which compound 4m was the most potent with IC50 of 3.79 μM, and compounds 4k, 4i, 4l, 4d, and 4n also demonstrated remarkable antitumor activity with IC50 of 3.79, 4.16, 4.36, 7.02, and 8.21 μM. We found three of the most potent compounds 4d, 4k, and 4l induced potent apoptosis and cell cycle arrest in HeLa cells, and compounds 4d and 4l significantly restrained the cell colony formation and showed moderate epidermal growth factor receptor (EGFR) inhibitory activity with IC50 of 13.01 and 1.76 μM. Therefore, these experiments indicate that these erlotinib-linked 1,2,3-triazole compounds are potential to act as effective anticancer agents against cervical cancer.

The Himalaya Plateau including Nepal is ‘greening up’ that has important implications to ecosystem services such as water supply, carbon sequestration, and local livelihoods. Understanding the combined causes behind greening is critical for effective policy makings in forest management and climate change adaptation towards achieving sustainable development goals. This national scale study comprehensively examined the natural and anthropogenic drivers of the long-term trend of vegetation dynamics across Nepal by correlation analysis and multiple linear regression analysis. We integrated multiple sources of data including global satellite-based leaf area index (LAI), climate data, landcover data, and forest land management information. Our study reveals a remarkable annual mean LAI increase of 22% (0.009 m ^2 m ^−2 yr ^−1 ) ( p < 0.05) from 1982 to 2020, with an acceleration in the rate of increase to 0.016 m ^2 m ^−2 yr ^−1 ( p < 0.05) after 2004. The community forestry (CF) program, forest area changes, and soil moisture availability accounted for 40%, 12%, and 10% of LAI temporal variability, respectively. Our analysis found soil moisture and forest area changes to be the primary drivers of the greening trend before 2004, while CF and forest expansion were the dominant factors thereafter. Additionally, interannual vegetation dynamics were significantly influenced by winter precipitation, incoming solar radiation, and pre-monsoon soil moisture. The projections based on four Earth System Models from Coupled Model Intercomparison Project Phase 6 suggest that Nepal’s greening trend is expected to continue at a rate of 0.009 m ^2 m ^−2 yr ^−1 ( p < 0.05) throughout the 21st century. We conclude that forest management program (CF) amid climate change that alters water and energy conditions have enhanced land greening, posing both opportunities and risks to ecosystem services in Nepal. This study provides much needed national-level information for developing forest management policies and designing Nature-based Solutions to respond to climate change and increasing demands for ecosystem services in Nepal.

Background Previous investigations have revealed that miR‐563 is associated with a number of diseases including the ossification of posterior longitudinal ligament, Parkinson's disease or drug resistance to leukemia. Yet, the role of miR‐563 and its molecular mechanism in the initiation and progression of cancers has not been previously explored. In this study, we aimed to provide clues to the function of miR‐563 and its direct target in lung cancer. Methods Online informatics software was applied to predict the target genes of miR‐563. MiR‐563 targeting LIN28B was evaluated through the luciferase reporter gene analysis. The effect of miR‐563 on LIN28B at the level of RNA and protein was detected using RT‐PCR and immunoblotting. The ability of proliferation of human lung cancer A549 was examined by MTT assay. RNA interference targeting LIN28B was examined through immunoblotting. The level of miR‐563 and LIN28B and their correlation were analyzed in 27 cases of lung tumor tissues by real‐time PCR. Results Oncogenic LIN28B was identified as one of the target genes of miR‐563 in lung cancer cells. MiR‐563 dose‐dependently decreased the LIN28B RNA level and subsequently its protein level in the cells. Cell proliferation was suppressed by ectopic miR‐563 expression and was accelerated after endogenous miR‐563 was knocked down by its inhibitor. However, silence in LIN28B reversed promotion of cell proliferation by the inhibition of miR‐563. In lung cancer tissues, miR‐563 was decreased and negative correlation of miR‐563 and LIN28B was shown. Conclusion MiR‐563 plays a tumor suppressive role in lung cancer progression via targeting oncogenic LIN28B.

Sleep is essential to the normal psychological and physiological activities of the human body. Increasing evidence indicates that sleep deprivation is associated with the occurrence, development, and poor treatment effects of various arrhythmias. Sleep deprivation affects not only the peripheral nervous system but also the central nervous system, which regulates the occurrence of arrhythmias. In addition, sleep deprivation is associated with apoptotic pathways, mitochondrial energy metabolism disorders, and immune system dysfunction. Although studies increasingly suggest that pathological sleep patterns are associated with various atrial and ventricular arrhythmias, further research is needed to identify specific mechanisms and recommend therapeutic interventions. This review summarizes the findings of sleep deprivation in animal experiments and clinical studies, current challenges, and future research directions in the field of arrhythmias.

Abstract A general polymer‐assisted spinodal decomposition strategy is used to prepare hierarchically porous sodium super ionic conductor (NASICON)‐structured polyanion‐type materials (e.g., Na3V2(PO4)3, Li3V2(PO4)3, K3V2(PO4)3, Na4MnV(PO4)3, and Na2TiV(PO4)3) in a tetrahydrofuran/ethanol/H2O synthesis system. Depending on the boiling point of solvents, the selective evaporation of the solvents induces both macrophase separation via spinodal decomposition and mesophase separation via self‐assembly of inorganic precursors and amphiphilic block copolymers, leading to the formation of hierarchically porous structures. The resulting hierarchically porous Na3V2(PO4)3 possessing large specific surface area (≈77 m2 g−1) and pore volume (≈0.272 cm3 g−1) shows a high specific capacity of 117.6 mAh g−1 at 0.1 C achieving the theoretical value and a long cycling life with 77% capacity retention over 1000 cycles at 5 C. This method presented here can open a facile avenue to synthesize other hierarchically porous polyanion‐type materials.

Background: Tetraspanins and integrins are integral membrane proteins. Tetraspanins interact with integrins to modulate the dynamics of adhesion, migration, proliferation, and signaling in the form of membrane domains called tetraspanin-enriched microdomains (TEMs). TEMs also contain other cell adhesion proteins like immunoglobulin superfamily (IgSF) proteins and claudins. Cardiovascular functions of these TEM proteins have emerged and remain to be further revealed.Objectives: The aims of this study are to explore the roles of these TEM proteins in the cardiovascular system using bioinformatics tools and databases and to highlight the TEM proteins that may functionally associate with cardiovascular physiology and pathology.Methods: For human samples, three databases—GTEx, NCBI-dbGaP, and NCBI-GEO—were used for the analyses. The dbGaP database was used for GWAS analysis to determine the association between target genes and human phenotypes. GEO is an NCBI public repository that archives genomics data. GTEx was used for the analyses of tissue-specific mRNA expression levels and eQTL. For murine samples, GeneNetwork was used to find gene–phenotype correlations and gene–gene correlations of expression levels in mice. The analysis of cardiovascular data was the focus of this study.Results: Some integrins and tetraspanins, such as ITGA8 and Cd151, are highly expressed in the human cardiovascular system. TEM components are associated with multiple cardiovascular pathophysiological events in humans. GWAS and GEO analyses showed that human Cd82 and ITGA9 are associated with blood pressure. Data from mice also suggest that various cardiovascular phenotypes are correlated with integrins and tetraspanins. For instance, Cd82 and ITGA9, again, have correlations with blood pressure in mice.Conclusion:ITGA9 is related to blood pressure in both species. KEGG analysis also linked ITGA9 to metabolism and MAPK signaling pathway. This work provides an example of using integrated bioinformatics approaches across different species to identify the connections of structurally and/or functionally related molecules to certain categories of diseases.

In this study, UiO-66 was selected as sorbent media packed in the tube to selectively enrich trace levels of benzene homologues such as benzene, toluene, and xylene (BTX) in ambient air prior to thermal desorption (TD)-GC-MS determination. A series of experiments were conducted to obtain the optimal TD conditions. The results indicated that the optimal TD parameters were as follows: desorption temperature of 180°C, desorption flow rate of 50 mL min−1, and desorption time of 30 min. Furthermore, the method based on UiO-66 enrichment integrated with TD-GC-MS for trace levels of BTX was successfully developed. It exhibited a good linearity (R2 > 0.99) in the range of 50–1000 ng, except for p, m-xylene in the range of 100–2000 ng, and achieved the recovery of 69.4–101.3%, and the relative standard deviation of 3.8–6.4%. The detection limits of BTX were 1.6–4.0 ng; according to 10 L of sampling volume, the method detection limits would be in the range of 0.16–0.40 µg m−3. Additionally, the method was successfully applied to determine BTX in indoor air and showed good selectivity and sensitivity. In summary, the findings in this work revealed that UiO-66 was an attractive adsorbent for selective enrichment trace levels of BTX compounds in ambient air, which was favorable for the subsequent detection by TD-GC-MS.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, with unmet need for the pharmacological therapy. The functions of ATXN7L3 in HCC progression are not known. Methods: RNA sequence, quantitative real-time PCR, and western blot were performed to detect gene expression. Chromatin immunoprecipitation was performed to detect possible mechanisms. Immunohistochemical stain was performed to examine the protein expression. Colony formation, cell growth curve and xenograft tumor experiments were performed to examine cell growth in vitro and in vivo. Findings: ATXN7L3 functions as a coactivator for ERα-mediated transactivation in HCC cells, thereby contributing to enhanced SMAD7 transcription. ATXN7L3 is recruited to the promoter regions of SMAD7 gene, thereby regulating histone H2B ubiquitination level, to enhance the transcription of SMAD7. A series of genes regulated by ATXN7L3 were identified. Moreover, ATXN7L3 participates in suppression of tumor growth. In addition, ATXN7L3 is lower expressed in HCC samples, and the lower expression of ATXN7L3 positively correlates with poor clinical outcome in patients with HCC. Interpretation: This study demonstrated that ATXN7L3 is a novel regulator of SMAD7 transcription, subsequently participating in inhibition of tumor growth in HCC, which provides an insight to support a previously unknown role of ATXN7L3 in HCC progression. Fund: This work was funded by 973 Program Grant from the Ministry of Science and Technology of China (2013CB945201), National Natural Science Foundation of China (31871286, 81872015, 31701102, 81702800, 81902889), Foundation for Special Professor of Liaoning Province, Natural Science Foundation of Liaoning Province (No.20180530072); China Postdoctoral Science Foundation (2019M651164).

BackgroundCoronavirus Disease 2019 (COVID-19) is an emerging and rapidly evolving disease, with no recommended effective anti-coronavirus drug treatment. Traditional Chinese Patent Medicines (CPMs) have, however, been widely used to treat COVID-19 in China, and a number of clinical practice results have shown them to have a significant role in its treatment. Consequently, numerous guidelines and expert consensus have recommended the use of CPMs to treat COVID-19.Aim of the StudyThe objectives of this review are to provide up-to-date information on the pharmacology and clinical research on CPMs in the treatment of COVID-19, discuss the research findings, and to better guide clinical application and scientific research on CPMs in the treatment of COVID-19.MethodsThe frequencies of CPM recommendations by guidelines and expert consensus for treatment of COVID-19 in China were ranked. This report identifies the top 10 CPMs, which include Huoxiang Zhengqi capsule (HXZQC), Lianhua Qingwen capsule (LHQWC), Jinhua Qinggan granule (JHQGG), Shufeng Jiedu capsule (SFJDC), Tanreqing injection (TRQI), Xiyanping injection (XYPI), Xuebijing injection (XBJI), Shenfu injection (SFI), Shengmai injection (SMI), and Angong Niuhuang pill (AGNHP). Relevant studies from 2000 to 2020 on these top 10 CPMs, covering usage, dosage, mechanism, curative effect, and precautions, were collected from pharmacopoeia, reports, and theses via library and digital databases (including PubMed, CNKI, Google Scholar, Web of Science, and Elsevier).ResultsThe properties of the top 10 CPMs included antiviral, antibacterial, anti-inflammatory, antipyretic and analgesic, anti-acute lung injury, anti-shock, immune regulation, and enhancement of pulmonary function. In addition, clinical research results and Chinese treatment data showed that the CPMs had good therapeutic efficacy in the treatment of COVID-19, and adverse reactions were minimal.ConclusionsKnowledge of the characteristics of the top 10 CPMs and precautions that should be taken may help clinicians to rationally improve therapeutic efficacy, and promote the role of Chinese Medicine in the control of the COVID-19 global epidemic.

Ephedra equisetina, the Nitraria species complex (N. sibirica, N. roborowskii and N. sphaerocarpa), and Rheum nanum are the main dietary plants of the Gobi Bear (Ursus arctos gobiensis), a subspecies of the brown bear, found in the Gobi desert of Mongolia. Their location and distribution range are closely related to the Gobi Bear survival. Analyzing the impact of climate change on the possible distribution of these species is essential for the future conservation and management of the Gobi Bear. In this study, we modeled the current and future distribution of the main dietary plants of the Gobi Bear based on one representative concentration pathway (RCP2.6) for the period from 2041 to 2060 (2050s) and 2061-2080 (2070s) using a maximum entropy (MaxEnt) species distribution model. Our results showed that the precipitation-associated variables had the strongest effect on the distributions of these species. Among these variables, the precipitation of the coldest quarter (Bio19) was the most important variable affecting the suitability of the habitats. Under the current climate conditions, the areas of the highly suitable (>0.6) habitat for E. equisetina, the Nitraria species complex, and R. nanum were 3,888.51, 23,727.78 and 13,816.88 km2, respectively, accounting for 8%, 52% and 30% of the Great Gobi “A” Strictly Protected Area. In the year 2050s and 2070s, the highly suitable habitat areas for E. equisetina and R. nanum will continue to increase and eventually reach to 23% and 36%, respectively. The Nitraria species complex would first be reduced to 33% in the 2050s and then increase to 36% in the 2070s. With the climate warming, the highly suitable habitats of the Gobi Bear’s main dietary plants would shift to the southeast. These results, together with previous studies about the Gobi Bear distribution can provide useful information and a reasonable reference for managers to put forward suggestions for better protection of the Gobi Bear.

Background: As a reader of histone H3K4me3, BPTF associated protein of 18 kDa (BAP18) is involved in modulation of androgen receptor action in prostate cancer. However, the function of BAP18 on oral squamous cell carcinoma (OSCC) and its molecular mechanism remains to be elusive. Methods: OSCC-derived cell lines carrying silenced BAP18 were established by Lentiviral infection. Quantitative PCR (qPCR), western blot, and ChIP assay were performed to detect gene transcription regulation and the possible mechanism. Colony formation, cell growth curve and xenograft tumor experiments were performed to examine cell growth and proliferation. Findings: Our study demonstrated that BAP18 was highly expressed in OSCC samples compared with that in benign. BAP18 depletion obviously influenced the expression of a series of genes, including cell cycle-related genes. We thus provided the evidence to demonstrate that BAP18 depletion significantly decreases CCND1 and CCND2 (CCND1/2) transcription. In addition, BAP18 is recruited to the promoter regions of CCND1/2, thereby facilitating the recruitment of the core subunits of MLL1 complex to the same regions, to increase histone H3K4me3 levels. Furthermore, BAP18 depletion delayed G1-S phase transition and inhibited cell growth in OSCC-derived cell lines. Interpretation: This study suggests that BAP18 is involved in modulation of CCND1/2 transcription and promotes OSCC progression. BAP18 could be a potential target for OSCC treatment and diagnosis. Fund: This work was funded by National Natural Science Foundation of China (31871286, 81872015, 31701102, 81702800, 81902889), Foundation for Special Professor of Liaoning Province, and Supported project for young technological innovation-talents in Shenyang (No. RC170541). Keywords: BAP18, CCND1/2, Transcription regulation, Histone methylation, Oral squamous cell carcinoma

Wildland fire seasons in the United States are getting longer, yet the impacts of fire on water availability at the regional scale are unclear. Here the authors show that fire increased annual river flow throughout the West, while prescribed burns in the subtropical Southeast had limited impact on river flow.