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The occupant behavior has a significant impact on the building performance. This review offers researchers and practitioners a clear understanding of the evolution of the occupant behavior model and its involvement in building optimization design, providing guidance for future research. Studies are selected if they are peer-reviewed conference proceedings and journal papers published from 2005 to 2023. By analyzing 203 core papers from the Web of Science, a bibliometric study is conducted using CiteSpace. The findings indicate that research on occupant behavior has advanced significantly since 2005, with China being the most active country. The interaction between occupant and building performance, development of occupant behavior model, building optimization framework, and optimized strategies in buildings are the four fundamental topics. Finally, the current challenges and future opportunities are discussed. Future research should focus on conducting real-case quantitative studies, expanding performance simulation, developing comprehensive techniques, improving user-system interaction, and exploring feasible social practices. However, limitations arise due to deficiencies in the thoroughness and depth of analyses resulting from sample constraints. To obtain more reliable results, a broader and more systematic approach to collecting publications is needed.

China’s reform began in the countryside, and rural reform began in Anhui. This study uses Anhui Province, China as an example in analyzing the impact of agricultural science and technology innovation resource allocation on rural revitalization, particularly by constructing an econometric model. Results indicate that the allocation of agricultural science and technology innovation resources has a steady positive impact on rural revitalization. Improvements in the allocation of agricultural science and technology innovation resources can effectively promote the development of rural revitalization and the spatial spillover of rural development, thereby facilitating the promotion of the spillover of neighboring areas to local rural development. A nonlinear relationship exists between allocation of agricultural science and technology innovation resources and rural revitalization. Lastly, rural revitalization can only be promoted substantially when the allocation of agricultural science and technology innovation resources reaches a certain condition.

The Yellow River basin (YRB) is a major ecological functional area in China, and its ecological safety development and change have extremely significant impacts on the natural environment and human society. However, existing studies on the YRB lack spatiotemporal characteristics analysis and prediction of ecological safety with vegetation as the core. Therefore, this study proposes to construct an ecological safety index (ESI) of the YRB based on the comprehensive multidimensional ecological safety evaluation system “vigor-pressure-state-response,” using the normalized difference vegetation index, vegetation carbon sink indicator parameters, temperature, precipitation, the digital elevation model, population density, and the per capita gross domestic product from 2000 to 2020. The spatiotemporal characteristics of the ESI were then analyzed for the YRB, and a long-term and short-term memory network model was constructed to predict the ESI trend of the YRB over the next 10 years. According to the results, from 2000 to 2020, the ESI of the YRB showed a fluctuating upward trend, and the annual average of the ESI changed abruptly in 2015 due to drastic changes in hazardous areas. The ESI in most areas of the YRB showed a significant upward trend, the stability of ESI changes was weak in some areas, and the overall spatial distribution showed significant positive spatial agglomeration characteristics. Further, the response of ESI to landscape complexity in different reaches of the YRB varied. Most of the middle reaches were positively correlated with landscape complexity, while most of the upper and lower reaches were not significantly or negatively correlated. Notably, over the next 10 years, YRB's ESI growth will slow down, with areas with degradation increasing, areas with significant growth decreasing, and areas currently showing stability improvement.

Agricultural scientific and technological innovation and rural industry integration are the key contents of promoting agricultural and rural modernization in China. This study empirically analyzed the matching relationship between the two and its influencing factors, and found that the matching degree between agricultural scientific and technological innovation and rural industry integration in China showed a steady upward trend in the sample period. Both China as a whole and all regions completed the upgrading from moderate to high matching in the sample period, The performance of each region is also excellent. In 2020, the matching degree of 28 regions will enter a high matching range. The implementation of the rural revitalization policy will help to improve the matching degree between China’s agricultural scientific and technological innovation and rural industrial integration. The scale of rural financial development and the matching degree of lagging one period also have a significant positive impact on the improvement of the matching degree. This study further proposes relevant policy recommendations from improving the supply level of agricultural scientific and technology innovation, enhancing the adaptability between supply and demand of agricultural scientific and technology innovation, improving the policy support system, and optimizing the financial security system.

Accurate landslide extraction is significant for landslide disaster prevention and control. Remote sensing images have been widely used in landslide investigation, and landslide extraction methods based on deep learning combined with remote sensing images (such as U-Net) have received a lot of attention. However, because of the variable shape and texture features of landslides in remote sensing images, the rich spectral features, and the complexity of their surrounding features, landslide extraction using U-Net can lead to problems such as false detection and missed detection. Therefore, this study introduces the channel attention mechanism called the squeeze-and-excitation network (SENet) in the feature fusion part of U-Net; the study also constructs an attention U-Net landside extraction model combining SENet and U-Net, and uses Sentinel-2A remote sensing images for model training and validation. The extraction results are evaluated through different evaluation metrics and compared with those of two models: U-Net and U-Net Backbone (U-Net Without Skip Connection). The results show that proposed the model can effectively extract landslides based on Sentinel-2A remote sensing images with an F1 value of 87.94%, which is about 2% and 3% higher than U-Net and U-Net Backbone, respectively, with less false detection and more accurate extraction results.

The anomalous movements of glaciers cause disasters, such as debris flows and landslides. It is very important to assess the glacier movements and their future trends. Glacier velocity refers to movement process. The current research aims to analyse past and current spatiotemporal changes in glacier velocity. No study has used neural network model to conduct a spatiotemporal prediction for glacier velocity. Therefore, this paper selected typical mountain glaciers G2 and G5 along the Sichuan-Tibet Railway as research objects and constructed the Convolutional Gate Recurrent Unit (ConvGRU) spatiotemporal prediction model based on 1988–2018 Landsat data to predict velocities in 2019–2028, and analysed the future trends of G2 and G5. The evaluation indexes met the model requirements to a large extent, quantitatively showing that the model has high accuracy and can successfully capture the fluctuation changes in time series data of glacier velocity. The mean deviations of G2 and G5 were 0.09 and −0.47 m/yr, respectively, reflecting the high reliability of the model applied to extraction of glacier velocity. The velocities of G2 and G5 showed a slow downtrend with fluctuations; that is, they will not cause damage to the construction and operation of the Sichuan-Tibet Railway in the short term.

Abstract Immunity-and-matrix-regulatory cells (IMRCs) derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix, which could be mass-produced with stable biological properties. Despite resemblance to mesenchymal stem cells (MSCs) in terms of self-renew and tri-lineage differentiation, the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined. Here, we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury. Following injection into the knees of rabbits with meniscal injury, IMRCs enhanced endogenous fibrocartilage regeneration. In the dose-escalating phase I clinical trial (NCT03839238) with eighteen patients recruited, we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting. Furthermore, the effective results of magnetic resonance imaging (MRI) of meniscus repair and knee functional scores suggested that 5 × 107 cells are optimal for meniscus injury treatment. In summary, we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury. Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.

Biotic and abiotic stresses have already seriously restricted the growth and development of Pinus massoniana, thereby influencing the quality and yield of its wood and turpentine. Recent studies have shown that C2H2 zinc finger protein transcription factors play an important role in biotic and abiotic stress response. However, the members and expression patterns of C2H2 TFs in response to stresses in P. massoniana have not been performed. In this paper, 57 C2H2 zinc finger proteins of P. massoniana were identified and divided into five subgroups according to a phylogenetic analysis. In addition, six Q-type PmC2H2-ZFPs containing the plant-specific motif ‘QALGGH’ were selected for further study under different stresses. The findings demonstrated that PmC2H2-ZFPs exhibit responsiveness towards various abiotic stresses, including drought, NaCl, ABA, PEG, H2O2, etc., as well as biotic stress caused by the pine wood nematode. In addition, PmC2H2-4 and PmC2H2-20 were nuclear localization proteins, and PmC2H2-20 was a transcriptional activator. PmC2H2-20 was selected as a potential transcriptional regulator in response to various stresses in P. massoniana. These findings laid a foundation for further study on the role of PmC2H2-ZFPs in stress tolerance.

N6-methyladenosine (m6A) RNA modification is the most prevalent form of RNA methylation and plays a crucial role in plant development. However, our understanding of m6A modification in Masson pine (Pinus massoniana Lamb.) remains limited. In this study, a complete analysis of m6A writers, erasers, and readers in Masson pine was performed, and 22 m6A regulatory genes were identified in total, including 7 m6A writers, 7 m6A erases, and 8 readers. Phylogenetic analysis revealed that all m6A regulators involved in Masson pine could be classified into three distinct groups based on their domains and motifs. The tissue expression analysis revealed that the m6A regulatory gene may exert a significant influence on the development of reproductive organs and leaves in Masson pine. Moreover, the results from stress and hormone expression analysis indicated that the m6A regulatory gene in Masson pine might be involved in drought stress response, ABA-signaling-pathway activation, as well as resistance to Monochamus alternatus. This study provided valuable and anticipated insights into the regulatory genes of m6A modification and their potential epigenetic regulatory mechanisms in Masson pine.

In the study, the shape, size and structure of the sightseeing elevators were investigated, and a prototypical model was established by Grasshopper. Furthermore, the performance and prices of glass were used to construct the function of price, then the multi-objective optimization method was adopted to simultaneously optimize the predicted percentage of people dissatisfied, useful daylight illuminance and cost of the building envelope of the elevators. The results showed that the optimal values of the total heat transfer coefficient, solar energy heat gain coefficient and total transmission of the envelope are 0.799 W/(m2·K), 0.164 and 0.153, respectively. Compared with that of “6 mm ultralow light transmission thermal reflective glass +12 mm air +6 mm transparent glass”, the predicted percentage of people dissatisfied decreases about 5.412 %. Though useful daylight illuminance has a small decrease of 1.167 %, cost of building envelope decreases by 60.127 %. In addition, the suitable working hours for three positions, where the control cabinets can be set at, have been significantly improved among the using frequency. In addition, ventilation systems were considered to improve the internal environment of sightseeing elevators, and appropriate control methods were selected to ensure the maximum operation of sightseeing elevators.

The literature has confirmed that when managers increase profits through earnings management, the readability of annual reports may be reduced Lo (2017), Ye (2018). Whether this conclusion is suitable for Chinese corporate social responsibility (CSR) reports, however, is still unclear. Based on the panel data of 5083 Chinese non-financial listed companies from 2010 to 2019, this paper adopts multiple linear regression to investigate the impact of earnings management on the readability of Chinese CSR reports. The results show that: (1) There is a significant negative correlation between earnings management and the readability of Chinese CSR reports, with the readability of Chinese annual reports as a mediating variable. (2) The negative effect is more significant when companies are not punished for violations, when the internal control index is low, when companies lack ISO14001 certification and when companies do not have independent third-party authentication for Chinese CSR reports. (3) When earnings management just exceeds zero, the readability of Chinese CSR reports decreases. (4) The economic consequences of reducing the readability of Chinese CSR reports are that financing costs are increased and environmental performance is decreased. To improve the quality of information disclosure of listed companies, the recommendations are as follows: First, the government should issue CSR reporting standards to reduce the manipulation of Chinese CSR reports. Second, Chinese CSR reports disclosed by listed companies must be audited by independent third parties to enhance the credibility of the information. Third, the company needs to strengthen its external and internal supervision to reduce the manipulation space for the readability of Chinese CSR reports. This study extends the negative relationship between earnings management and the readability from annual reports to Chinese CSR reports. To prevent investors from detecting earnings management, the readability of Chinese CSR reports may be reduced. At the same time, the study has definitely added value to the existing literature in the domain of CSR.

Objective. Large-scale studies on the characteristics and management of abdominal trauma in megacities in China are lacking. The aim of this study was to analyze and present the clinical patterns and treatment status of abdominal trauma in regional medical centers. Methods. Cases of abdominal trauma treated at seven medical centers in Beijing from 2010 to 2021 were collected. Clinical information about age, sex, injury cause, geographic distribution, abbreviated injury scale/injury severity score (AIS/ISS) value, injury-hospital time, preoperative time, surgically identified organ injuries, type of surgery, causes of reoperation and 90-day mortality was included in this study. Clinical characteristics, treatment methods, and short-term prognoses (90-days survival) were compared between blunt abdominal trauma (BAT) and penetrating abdominal trauma (PAT) cases. Non-normally distributed data are described as medians (IQR), and the Mann‒Whitney U test was performed; qualitative data were analyzed using the X2 test. Univariate and multivariate survival analyses were performed by the Cox proportional hazards model. Results. A total of 553 patients (86.98% male) with a median age of 36.50 (27.00–48.00) years were included. The BAT group had a significantly higher proportion of serious injury (P=0.001), lower initial hemoglobin level (P=0.001), and a lower laparoscopy surgery rate (P=0.044) compared to the PAT group. Additionally, more BAT cases were from the area around Beijing (P=0.008) and a longer injury-regional hospital time (10.47 (5.18–22.51) hours vs. 7.00 (3.80–15.38) hours, P=0.001). In the hollow viscus injury subgroup, the BAT group had a significantly longer injury-regional hospital time and preoperative time compared to the PAT group (injury-regional hospital time: 10.23 (6.00–21.59) hours vs. 7.07 (3.99–13.85) hours, P=0.002; preoperative time: 3.02 (2.01–5.58) hours vs. 2.81 (1.85–3.63) hours, P=0.047). The overall 90-day mortality was 11.9%, and longer injury-regional hospital time (HR: 1.01, 95% CI: 1.00–1.02, P=0.008), receipt of ICU treatment (HR: 4.69, 95% CI: 2.54–8.65, P=0.001), and severe ISSs (ISS > 25 vs. ISS

Abstract Poor survival and restricted function of transplanted stem cells are regarded as limiting their efficacy in wound recovery greatly. Consequently, it is necessary to identify innovative therapeutic strategies to solve these issues. Firstly, the biological effect of PF-127 hydrogel alone and in combination with SAP on the survival, and migration of cultured HUCMSCs was assessed by cell viability, apoptosis, and scratch wound assays. S. aureus and E. coli were used to evaluate the antibacterial activity of PF-127 plus SAP combination. Further, the ability of HUCMSCs-conditioned medium (HUCMSCs-CM) to promote the angiogenesis and migration of human umbilical vein endothelial cells (HUVECs) in vitro was evaluated using tube formation and transwell migration assays. Finally, the HUCMSCs embedded in PF-127 plus SAP scaffold were administered onto mice’s excisional cutaneous wound bed. Histological and immunohistochemical analyses were employed to investigate the wound healing capacity as well as cellular responses of PF-127/HUCMSCs/SAP hydrogel. PF-127 showed cytotoxicity on HUCMSCs, whereas the addition of SAP significantly promoted cell viability and alleviated apoptosis of HUCMSCs encapsulated in PF-127 hydrogel in vitro. SAP supplementation substantially abrogated the inhibiting effect of PF-127 on the migration of HUCMSCs in vitro. The combination of PF-127 and SAP exerted an obvious bacteriostatic function on S. aureus and E. coli. Moreover, the co-treatment with SAP could remarkably enhance the stimulative effect of HUCMSCs-CM on the angiogenesis and migration of HUVECs in vitro. PF-127 combined SAP-embedded HUCMSCs transplantation resulted in a potently accelerated wound healing process, promoted the number of proliferating cells and newly formed blood vessels, as well as enhanced expression of vascular endothelial growth factor. PF-127 coupled with SAP contributes to HUCMSCs-mediated traumatic wound closure in mice by promoting cell survival, antibacterial action, and angiogenesis. Our results offered a theoretical foundation for the clinical treatment of traumatic skin defects.

N6-methyladenosine (m6A) is one of the most abundant chemical modifications on mRNA in eukaryotes. RNA-binding proteins containing the YT521-B (YTH) domain play crucial roles in post-transcriptional regulation of plant growth, development, and stress response by reading the m6A mark. However, the YTH domain-containing RNA-binding protein family has not been studied in a valuable and medicinal tree such as Cinnamomum camphora (C. camphora) yet. In this study, we identified 10 YTH genes in C. camphora, located on eight out of 12 chromosomes. Phylogenetic analysis revealed that these genes can be classified into two major classes, YTHDF (CcDF) and YTHDC (CcDC). Closely related CcYTHs within the same class exhibited a similar distribution of conserved motifs and domain organization, suggesting functional similarities among these closely related CcYTHs. All CcYTH proteins possessed a highly conserved YTH domain, with CcDC1A containing an additional CCCH domain. The liquid–liquid phase separation (LLPS) predictions indicate that CcDC1A, CcDF1A, CcDF1C, CcDF3C, CcDF4C, and CcDF5C may undergo phase transitions. Quantitative expression analysis revealed that tissue-specific expression was observed fo CcYTHs. Notably, there were two genes, CcDF1A and CcDF5C; both exhibited significantly higher expression levels in various tissues than other genes, indicating that the m6A-YTH regulatory network in C. camphora might be quite distinct from that in most plants such as Arabidopsis thaliana (A. thaliana) with only one abundant YTH protein. According to the analysis of the up-stream cis-regulatory elements of these YTH genes, these genes could be closely related to stress, hormones, and development. The following stress response experiments further verified that their expression levels indeed changed under both PEG and NaCl treatments. These findings not only provide a foundation for future functional analysis of CcYTHs in C. camphora, but also provide insights into the functions of epigenetic mark m6A in forest trees.

N6-methyladenosine (m6A) is essential for RNA metabolism in cells. The YTH domain, conserved in the kingdom of Eukaryotes, acts as an m6A reader that binds m6A-containing RNA. In plants, the YTH domain is involved in plant hormone signaling, stress response regulation, RNA stability, translation, and differentiation. However, little is known about the YTH genes in tea-oil tree, which can produce edible oil with high nutritional value. This study aims to identify and characterize the YTH domains within the tea-oil tree (Camellia chekiangoleosa Hu) genome to predict their potential role in development and stress regulation. In this study, 10 members of the YTH family containing the YTH domain named CchYTH1-10 were identified from C. chekiangoleosa. Through analysis of their physical and chemical properties and prediction of subcellular localization, it is known that most family members are located in the nucleus and may have liquid–liquid phase separation. Analysis of cis-acting elements in the CchYTH promoter region revealed that these genes could be closely related to abiotic stress and hormones. The results of expression profiling show that the CchYTH genes were differentially expressed in different tissues, and their expression levels change under drought stress. Overall, these findings could provide a foundation for future research regarding CchYTHs in C. chekiangoleosa and enrich the world in terms of epigenetic mark m6A in forest trees.

Abstract Background To compare the biomechanical properties and stability, using a finite element model, of four fixation constructs used for the treatment of anterior column and posterior hemi-transverse (ACPHT) acetabular fractures under two physiological loading conditions (standing and sitting). Methods A finite element model simulating ACPHT acetabular fractures was created for four different scenarios: a suprapectineal plate combined with posterior column and infra-acetabular screws (SP-PS-IS); an infrapectineal plate combined with posterior column and infra-acetabular screws (IP-PS-IS); a special infrapectineal quadrilateral surface buttress plate (IQP); and a suprapectineal plate combined with a posterior column plate (SP-PP). Three-dimensional finite element stress analysis was performed on these models with a load of 700 N in standing and sitting positions. Biomechanical stress distributions and fracture displacements were analysed and compared between these fixation techniques. Results In models simulating the standing position, high displacements and stress distributions were observed at the infra-acetabulum regions. The degree of these fracture displacements was low in the IQP (0.078 mm), as compared to either the IP-PS-IS (0.079 mm) or the SP & PP (0.413 mm) fixation constructs. However, the IP-PS-IS fixation construct had the highest effective stiffness. In models simulating the sitting position, high fracture displacements and stress distributions were observed at the regions of the anterior and posterior columns. The degree of these fracture displacements was low in the SP-PS-IS (0.101 mm), as compared to the IP-PS-IS (0.109 mm) and the SP-PP (0.196 mm) fixation constructs. Conclusion In both standing and sitting positions, the stability and stiffness index were comparable between the IQP, SP-PS-IS, and IP-PS-IS. These 3 fixation constructs had smaller fracture displacements than the SP-PP construct. The stress concentrations at the regions of quadrilateral surface and infra-acetabulum suggest that the buttressing fixation of quadrilateral plate was required for ACPHT fractures.

ABSTRACTCytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical inhibitory checkpoint molecule, and monoclonal antibodies (mAbs) targeting CTLA-4 that restore anti-tumor T cell immunity have achieved clinical success. Here, we report a humanized IgG1 mAb, namely JS007, with high binding affinity to CTLA-4. JS007 shows superior binding affinity and T-cell activating efficiency over ipilimumab. Moreover, it demonstrates substantial in vivo tumor suppression efficacy at low doses. The crystal structure of JS007/CTLA-4 complex (PDB: 8HIT) shows JS007 adopts a heavy-chain-dominant binding mode, and mainly contacts the BC loop, DE loop and FG loop of CTLA-4. Notably, two Tyr residues (VH-Y100 and VL-Y32) from the complementarity-determining region loops insert into the two cavities formed by the residues from the loops of CTLA-4, which may contribute to the stabilization of the binding. Comparative analysis with other anti-CTLA-4 mAbs indicates that the double “wedge-into-hole” binding mode is unique for JS007 and may be responsible for the high-affinity binding to CTLA-4. These findings have provided an important molecular understanding of the high-affinity CTLA-4 blockade mAbs and shed light on future development of agents targeting CTLA-4.

IntroductionThe average carbon storage of Pinus massoniana is much higher than the average carbon storage of Chinese forests, an important carbon sink tree species in subtropical regions of China. However, there are few studies on the differences in rhizosphere microorganisms of P. massoniana with different carbon storages.MethodsTo clarify the relationships between plant carbon storage level, environmental parameters and microbial community structure, we identified three carbon storage levels from different P. massoniana provenances and collected rhizosphere soil samples. We determined chemical properties of soil, extracellular enzyme activity, and microbial community structures at different carbon storage levels and examined how soil factors affect rhizosphere microorganisms under different carbon storage levels.ResultsThe results revealed that soil organic carbon (SOC), nitrate nitrogen (NO3−-N), ammonium nitrogen (NH4+-N) contents all increased with increasing carbon storage levels, while pH decreased accordingly. In contrast, the available phosphorus (AP) content did not change significantly. The soil AP content was within the range of 0.91 ~ 1.04 mg/kg. The microbial community structure of P. massoniana changed with different carbon storage, with Acidobacteria (44.27%), Proteobacteria (32.57%), and Actinobacteria (13.43%) being the dominant bacterial phyla and Basidiomycota (73.36%) and Ascomycota (24.64%) being the dominant fungal phyla across the three carbon storage levels. Soil fungi were more responsive to carbon storage than bacteria in P. massoniana. C/N, NH4+-N, NO3−-N, and SOC were the main drivers (p

Abstract Background Ulcerative colitis (UC), a chronic inflammatory disease, is caused by abnormal immune system reactions resulting in inflammation and ulcers in the large intestine. Phillygenin (PHI) is a natural compound found in Forsythia suspensa (Thunb.) Vahl, which is known for its antipyretic, anti‐inflammatory, antiobesity, and other biological activities. However, the therapeutic role and molecular mechanisms of PHI on UC are still insufficiently researched. Methods In this study, dextran sulfate sodium (DSS) and 2.5% 2,4,6‐trinitro‐Benzenesulfonic acid (TNBS)‐induced acute UC were used to investigate the therapeutic effects of PHI. We evaluated the effects of PHI on disease activity index (DAI), body weight, mortality, intestinal mucosal barrier, cytokine secretion, and macrophage infiltration into colon tissue using various techniques such as flow cytometry, immunofluorescence, enzyme‐linked immunosorbent assay (ELISA), RT‐qPCR, and Western blot analysis. Results Our findings revealed that PHI has therapeutic properties in UC treatment. PHI was able to maintain body weight, reduce DAI and mortality, restore the intestinal mucosal barrier, and inhibit cytokine secretion. Flow cytometry assay and immunofluorescence indicated that PHI reduces macrophage infiltration into colon tissue. Mechanistically, PHI may exert anti‐inflammatory effects by downregulating the TLR4/MyD88/NF‐κB pathway and inhibiting the activation of NLRP3 inflammasome. Conclusion In conclusion, PHI possesses significant anti‐inflammatory properties and is expected to be a potential drug for UC treatment. Our study delves into the underlying mechanisms of PHI therapy and highlights the potential for further research in developing PHI‐based treatments for UC.

Summary: Skeletal muscle function declines in the aging process or disease; however, until now, skeletal muscle has remained one of the organs most undertreated with medication. In this study, naringenin (NAR) was found to build muscle endurance in wild-type mice of different ages by increasing oxidative myofiber numbers and aerobic metabolism, and it ameliorates muscle dysfunction in mdx mice. The transcription factor Sp1 was identified as a direct target of NAR and was shown to mediate the function of NAR on muscle. Moreover, the binding site of NAR on Sp1 was further validated as GLN-110. NAR enhances the binding of Sp1 to the CCCTGCCCTC sequence of the Esrrg promoter by promoting Sp1 phosphorylation, thus upregulating Esrrg expression. The identification of the Sp1-ERRγ transcriptional axis is of great significance in basic muscle research, and this function of NAR has potential implications for the improvement of muscle function and the prevention of muscle atrophy.

WUSCHEL-related homeobox (WOX) transcription factors (TFs) play a crucial role in regulating plant development and responding to various abiotic stresses. However, the members and functions of WOX proteins in Pinus massoniana remain unclear. In this study, a total of 11 WOX genes were identified, and bioinformatics methods were used for preliminary identification and analysis. The phylogenetic tree revealed that most PmWOXs were distributed in ancient and WUS clades, with only one member found in the intermediate clade. We selected four highly conserved WOX genes within plants for further expression analysis. These genes exhibited expressions across almost all tissues, while PmWOX2, PmWOX3, and PmWOX4 showed high expression levels in the callus, suggesting their potential involvement in specific functions during callus development. Expression patterns under different abiotic stresses indicated that PmWOXs could participate in resisting multiple stresses in P. massoniana. The identification and preliminary analysis of PmWOXs lay the foundation for further research on analyzing the resistance molecular mechanism of P. massoniana to abiotic stresses.

Abstract Objective Flail arm syndrome (FAS) is one of the atypical subtypes of amyotrophic lateral sclerosis (ALS). Mutations in hnRNPA1 encoding heterogeneous nuclear ribonucleoprotein (hnRNP) A1 are a rare genetic cause of ALS. Herein, marked clinical heterogeneity of FAS in a pedigree with a known hnRNPA1 variant was described to raise early awareness of the ALS variant. Furtherly, a literature review of the hnRNPA1‐related spectrum was made to summarize the clinical and genetic characteristics. Methods Detailed clinical evaluation, muscle pathology, and whole‐exome sequencing were performed. The sequence and co‐segregation of the mutation among the family members were confirmed by Sanger sequencing. Results The great clinical variability was found in a FAS pedigree. Muscle pathology revealed a cluster distribution of angulated or rounded atrophic fibers, accompanied by significant multi‐nucleus aggregation. Immunohistochemical staining showed that mutant hnRNPA1 proteins accumulated in muscle fiber cytoplasm. Exome sequencing identified a documented variant in hnRNPA1 gene c.1018C > T (p.P340S), which co‐segregated with disease in the family. Besides, highly phenotypic heterogeneity was also found in other hnRNPA1‐related diseases. Interpretation We described a Chinese pedigree with hnRNPA1‐related FAS, which showed significant clinical variability among the intrafamilial members. FAS is a relatively milder variant of ALS, due to the highly heterogeneous clinical spectrum, early observation is of paramount importance. In addition, the highly phenotypic heterogeneity and molecular genetic mechanism of the hnRNPA1‐related spectrum are still beyond fully understood. Further, the detailed molecular mechanism underlying the clinical diversity is warranted to be explored.

Objectives In geriatric acetabular fractures, the quadrilateral surface (QLS) was frequently involved in acetabular fracture patterns and accompanied by medial displacement. It was important to buttress the medial displaced QLS and reconstruct the congruity of the affected acetabulum. To evaluate the clinical effectiveness of the novel infra‐pectineal quadrilateral surface buttress plates for the treatment of geriatric acetabular fractures. Methods Twenty‐three geriatric patients who were treated for acetabular fractures involving QLS with the novel infra‐pectineal buttress plates (NIBP) through a single supra‐ilioinguinal approach between January 2015 and June 2019 were retrospectively analyzed; all patients received at least 1 year's follow‐up. All patients were aged ≥60 years old and including 18 males and five females. Radiologic and clinical outcomes of patients involved in the study were collated and analyzed according to the Matta scoring system and the Merle D'Aubigné–Postel scoring system. The functional recovery scoring was compared using q‐test. Results All 23 consecutive patients had relatively satisfactory clinical treatment effectiveness. Average ages, length of incision, operation time, and intraoperative blood loss were 69.8 ± 6.1 years, 12.1 ± 2.6 cm, 166.5 ± 43.5 min, and 500 (500,700) ml, respectively. According to the Matta scoring system, 14 cases of reduction were graded as excellent, five as good, and four as fair. At the last follow‐up, the clinical outcome evaluation was excellent in 13 cases, good in seven cases, and poor in three cases with the use of the Merle D'Aubigné–Postel scoring system. The difference of modified Merle D'Aubigne‐Postel score at 3 months, 6 months and last follow up was statistically significant (F = 21.56, p

Pinus massoniana is an important coniferous tree species for barren mountain afforestation with enormous ecological and economic significance. It has strong adaptability to the environment. TEOSINTE BRANCHED 1/CYCLOIDEA/PCF (TCP) transcription factors (TFs) play crucial roles in plant stress response, hormone signal transduction, and development processes. At present, TCP TFs have been widely studied in multiple plant species, but research in P. massoniana has not been carried out. In this study, 13 PmTCP TFs were identified from the transcriptomes of P. massoniana. The phylogenetic results revealed that these PmTCP members were divided into two categories: Class I and Class II. Each PmTCP TF contained a conserved TCP domain, and the conserved motif types and numbers were similar in the same subgroup. According to the transcriptional profiling analysis under drought stress conditions, it was found that seven PmTCP genes responded to drought treatment to varying degrees. The qRT-PCR results showed that the majority of PmTCP genes were significantly expressed in the needles and may play a role in the developmental stage. Meanwhile, the PmTCPs could respond to several stresses and hormone treatments at different levels, which may be important for stress resistance. In addition, PmTCP7 and PmTCP12 were nuclear localization proteins, and PmTCP7 was a transcriptional suppressor. These results will help to explore the regulatory factors related to the growth and development of P. massoniana, enhance its stress resistance, and lay the foundation for further exploration of the physiological effects on PmTCPs.

N6-methyladenosine (m6A) is becoming one of the most important RNA modifications in plant growth and development, including defense, cell differentiation, and secondary metabolism. YT521-B homology (YTH) domain-containing RNA-binding proteins, identified as m6A readers in epitranscriptomics, could affect the fate of m6A-containing RNA by recognizing and binding the m6A site. Therefore, the identification and study of the YTH gene family in Liriodendron chinense (L. chinense) can provide a molecular basis for the study of the role of m6A in L. chinense, but studies on the YTH gene in L. chinense have not been reported. We identified nine putative YTH gene models in the L. chinense genome, which can be divided into DF subgroups and DC subgroups. Domain sequence analysis showed that the LcYTH protein had high sequence conservation. A LcYTH aromatic cage bag is composed of tryptophan and tryptophan (WWW). PrLDs were found in the protein results of YTH, suggesting that these genes may be involved in the process of liquid–liquid phase separation. LcYTH genes have different tissue expression patterns, but the expression of LcYTHDF2 is absolutely dominant in all tissues. In addition, the expression of the LcYTH genes is changed in response to ABA and MeJA. In this study, We identified and analyzed the expression pattern of LcYTH genes. Our results laid a foundation for further study of the function of the LcYTH gene and further genetic and functional analyses of m6A RNA modification in forest trees.

Introduction: Flat dosing regimen has recently been approved for programmed death receptor-1 (PD-1) inhibitors including toripalimab, nivolumab and pembrolizumab. The objective of this study is to provide pharmacological evidence for a flat dosing regimen of toripalimab by assessing the efficacy and safety profile of a 240 mg Q3W flat dose relative to the currently approved 3 mg/kg Q2W.Methods: A population pharmacokinetic (PopPK) model was established based on 1,014 evaluable patients in 13 clinical studies. The exposure-objective response rate (ORR, n = 234) and exposure-safety (n = 152) analyses were performed by logistic regression. Three safety endpoints including grade ≥ 3 adverse events (AEs), treatment-related grade ≥ 3 AEs, and AEs leading to study drug discontinuation were evaluated. Progression-free survival (PFS, n = 234) was evaluated using a Cox proportional hazard model with the Kaplan-Meier survival curve.Results: The PK profiles of toripalimab are best described by a two-compartment model with time-varying clearance characterized by a sigmoidal maximum effect (Emax) function. Simulations for the first dose and steady-state exposures for the 240 mg Q3W dosing regimen were comparable to those for the 3 mg/kg Q2W dosing regimen with 95% exposure coverage ranging from 88% to 96%. The exposure-safety analysis showed that the probability of an adverse event occurring did not increase with increases in toripalimab exposure. A flat exposure-response relationship for ORR was identified. The Kaplan–Meier survival curve showed that exposure was a predictor for PFS; however, no difference in treatment benefit was demonstrated across exposure quantiles using a Cox proportional hazard model.Discussion: This study revealed that toripalimab exposure of 240 mg Q3W dosing regimen was comparable to 3 mg/kg Q2W dosing regimen. The safety and efficacy E-R results of 240 mg Q3W is flat. Hence, the 240 mg Q3W dosing regimen is determined to be a preferred therapeutic dosage for toripalimab due to the convenience of flat dose.

IntroductionDigestive system pan-cancer is one of the lethal malignant tumors, which have the propensity for poor prognosis and difficult treatment. Endoplasmic reticulum (ER) stress has served as a pivotal role in the progression of the tumor, while the implication of ER stress on digestive system pan-cancers still needs elucidation, especially from the perspective of clinical outcome and that of genomic features.MethodsFirst, Among the ER STRESS factors from the REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR (113 genes) and HALLMARK_UNFOLDED_PROTEIN_RESPONSE (92 genes) terms, 153 ER STRESS regulators were identified after removing replicates. The somatic mutation data and copy number variation data of gastrointestinal pan-cancer were downloaded from The Cancer Genome Atlas (TCGA) database. Then, we explored the clinical outcome and genetic mutation of ER stress-related differentially expressed genes (DEGs) by multiple bioinformatics analysis. Subsequently, we analyzed the Spearman correlation between the drug sensitivity of 179 gastrointestinal anticancer drugs and the transcriptional expression of 153 ER stress factors in 769 cancer cell lines of the GDSC2 cohort. Next, ssGSEA method was used to quantify the immune cell infiltration scores in the tumor microenvironment, and Spearman correlation was used to calculate the correlation between ER stress scores and immune cell infiltration. Finally, we analyzed the cellular origin of ER stress factor dysregulation.ResultsWe analyzed the genomic changes and clinical outcomes of ER stress factors in different tumors of gastrointestinal pan-cancer. Endoplasmic reticulum stress factor (ER) in digestive tract tumors showed high SNV mutation frequency, less methylation dysregulation and was associated with multiple oncogenic pathways. Endoplasmic reticulum stress factor (ER) is a risk factor for many cancers, but the effect on overall survival in rectal adenocarcinoma is opposite to that in other gastrointestinal tumors. And ER stress factors are highly correlated with drugs that target important pathways.DiscussionBased on the clinical prognosis and genomic analysis of ER stress-related factors in patients with gastrointestinal pan-cancer, this study provides a new direction for further research on gastrointestinal pan-cancer.

Surface deformation poses a great threat to the safety of Jinchuan mining area production activities. At present, the spatio-temporal evolution law and mechanism of surface deformation in the Jinchuan mining area are unclear, and it is difficult to obtain reliable prediction results using the existing spatio-temporal prediction methods due to the lack of model parameters or relevant data. To solve these problems, this study proposes a new unified convolutional neural network with peephole long short-term memory (CNN-PhLSTM). Small baseline subset interferometric synthetic aperture radar (SBAS-InSAR) technology was used to obtain the spatio-temporal evolution characteristics of surface deformation in the period of 2014–2021. Time series InSAR deformation data are merged into a unified network model in series with a time-distributed CNN segmentation and stacked PhLSTM. The InSAR measurement results are shown to be reliable by comparison and verification with the benchmark and InSAR results of different orbits. The proposed CNN-PhLSTM model was evaluated by mean absolute error and structural similarity (SSIM) evaluation indexes, and was compared with support vector regression (SVR), multilayer perceptron (MLP) and CNN-LSTM models. The results show three continuous subsidence areas, namely the Longshou, second western and third eastern mining areas. The cumulative surface deformation continued to increase from 2014 to 2021. Faults and lithology control the spatial distribution of surface deformation in the Jinchuan mining area. The prediction results demonstrate that the surface deformation range will continue to expand and that time-series surface deformation will show a slow deceleration trend in the next two years.

Accurate and comprehensive vegetation prediction methods are essential for effective agricultural planning and budgeting. Most existing vegetation prediction methods rely on sampling points rather than on overall spatiotemporal characteristics, making it difficult to accurately forecast vegetation changes. Hence, we built a neural network model with encoding and decoding modules based on a convolution gate recurrent unit (ConvGRU) and applied it to spatiotemporal normalized difference vegetation index (NDVI) predictions for the upper Heihe river basin (UHRB) in the Qilian Mountains, China. Based on MODIS NDVI raster data for the UHRB for 2000–2020, the analysis of the region's spatiotemporal characteristics showed that the NDVI varied significantly over time. To avoid the gradient disappearance problem during ConvGRU model prediction, we proposed several numerical scaling methods for preprocessing the data before conducting training and prediction. We then constructed a spatiotemporal prediction model based on the ConvGRU, trained and predicted the numerically scaled data, and used various metrics to evaluate the model. The results showed that the grouping tanh-ln function fitting was the least erroneous, and the ConvGRU model using data scaled by this method performed well across various metrics according to the test-set results. Also, unlike traditional time series prediction methods, the model accounted for spatiotemporal correlation features, and the output data of the prediction model were continuous and intuitive. Therefore, the proposed method is suitable for predicting dynamic vegetation changes. The NDVI prediction trend analysis indicated that the vegetation in the UHRB should improve in the future.

Interferometric phase filtering is a crucial step in the interferometric synthetic aperture radar (InSAR) data processing, which is also important for improving the accuracy of topography mapping and deformation monitoring. Most of the commonly used phase filtering methods perform windowing computations based on the statistical characteristics of a single interferogram in the spatial or frequency domain. However, the difficulty in taking into account the diversity and complexity of the phase image results in filtering methods with weak denoising, limited detail preservation, and poor generalization ability. At the same time, regardless of the spatial or frequency domain, improved phase filtering performance inevitably leads to the problem of declining effectiveness. This article proposes a phase filtering method based on the deep convolution neural network with multiscale feature dynamic fusion (MSFF). Unlike the traditional feedforward neural networks, the proposed method adopts a strategy of multiscale feature dynamic fusion that accounts for the deep and shallow features of the interferometric phase while also taking into account image detail preservation and noise suppression during phase filtering. Based on both subjective and objective evaluations, the experimental results using the simulated data prove that the proposed method has better noise suppression and detail preservation than the commonly used methods and that the filtering performance is less dependent on noise level. Experiments using the real data confirm that the proposed method has better generalization ability and can meet the precision requirements of practical applications. The method presented in this article can provide a new approach for research in high-precision InSAR data processing technology while also offering technical support for practical InSAR applications.

Phenylpropanoids are crucial for the growth and development of plants and their interaction with the environment. As key transcriptional regulators of plant growth and development, MYB-like transcription factors play a vital role in the biosynthesis of phenylpropanoid metabolites. In this study, we functionally characterized PmMYB6, a Pinus massoniana gene that encodes an R2R3-MYB transcription factor. It was confirmed by qPCR that PmMYB6 was highly expressed in the flowers, xylem, and phloem of P. massoniana. By overexpressing PmMYB6 in tobacco and poplar, we found that transgenic plants had enlarged xylem, increased content of lignin and flavonoids, and up-regulated expression of several enzyme genes of the phenylpropane metabolism pathway to different degrees. The above research results indicate that PmMYB6 is involved in the metabolic flux distribution of different branches of the phenylpropane metabolic pathway, and the results may provide clues for the regulation of metabolic fluxes between flavonoids and the lignin biosynthesis pathways of P. massoniana, as well as provide a basis for the molecular breeding of P. massoniana.

Pinus massoniana is a major fast-growing timber tree species planted in arid areas of south China, which has a certain drought-resistant ability. However, severe drought and long-term water shortage limit its normal growth and development. Therefore, in this study, physiological indices, and the transcriptome sequencing and cloning of AP2/ERF transcription factor of P. massonsiana were determined to clarify its molecular mechanism of drought stress. The results showed that stomatal conductance (Gs) content was significantly decreased, and superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and abscisic acid (ABA) content were significantly increased under drought stress. Transcriptomic analysis revealed that compared to the control, 9, 3550, and 4142 unigenes with differential expression were identified by comparing plants subjected to light, moderate or severe drought. AP2/ERF with high expression was screened out for cloning. To investigate the biological functions of ERF1, it was over-expressed in wild-type Populus davdianaand × P. bolleana via the leaf disc method. Under drought stress, compared to wild-type plants, ERF1 over-expressing poplar lines (OE) maintained a higher photosynthetic rate and growth, while the transpiration rate and stomatal conductance significantly decreased and water use efficiency was improved, indicating that drought tolerance was enhanced. This study provides an insight into the molecular mechanism of drought stress adaptation in P. massoniana.

The paper reports the result of an investigation on the effectiveness of afterschool program management in Taiwan that was conducted in the Yonglin Hope School through an in-depth investigation consisting of observations, interviews and questionnaire. The involved participants were the director of Institute for Disadvantaged Students’ Learning (IDSL), Yonglin Foundation, school principal, social workers, and tutors. This study found five main factors that contribute toward the effectiveness of afterschool program management in Yonglin Hope School, namely setting specific goals, having professional development and training, continuous evaluation, class sizes and designed curriculum. In addition, the effectiveness of the afterschool program was supported by five main activities (i.e., remedial teaching, homework assistance, English summer camp, special event and field trips) to improve the students’ knowledge and experience. Furthermore, it was also supported by an integrated and interconnected role of different stakeholders (i.e., Yonglin Foundation, Institute for Disadvantaged Students’ Learning, school principals, social workers and tutors) who played an important role to make this program being success. Importantly, tutors as the main actor played the most important role to improve students’ achievements.

Abstract Background Colorectal cancer is a common malignancy occurring in the digestive system and ranks second in cancer mortality worldwide. In colorectal cancer, hydrogen sulfide (H2S) is selectively upregulated, resulting in the further exacerbation of the disease. Therefore, the clearance of H2S and the regulation of the enzymes on the H2S pathways are of great significance for colorectal cancer therapy. Methods Here, we investigated the H2S content in various clinical tumor tissues from patients and confirmed that overproduced concentration of H2S in colorectal cancer. Accordingly, we developed an H2S-responsive nanoplatform based on zinc oxide coated virus-like silica nanoparticles (VZnO) for the therapy of colorectal cancer. Results Owing to its excellent H2S scavenging ability, VZnO could effectively reduce H2S content in colorectal cancer to prohibit the growth of CT26 and HCT116 colorectal cancer cells. Moreover, the removal of H2S in colorectal cancer also leads to tumor inhibition through activating ferroptosis, a non-apoptotic form of cell death. The biosafety-related toxicological and pathological analysis confirmed the low toxicity and high safety of VZnO in colorectal cancer treatment. Furthermore, as an H2S-responsible nanosystem, VZnO appears to have no therapeutic effect on other non H2S rich cancers, such as the 4T1 breast cancer model. Conclusions We anticipate that the H2S-depletion-induced ferroptosis strategy using zinc oxide-based nanomaterials would provide insights in designing nanomedicines for colorectal cancer-target theranostics and may offer clinical promise. Graphic abstract

Abstract This multicenter phase-II trial aimed to investigate the efficacy, safety, and predictive biomarkers of toripalimab plus chemotherapy as second-line treatment in patients with EGFR-mutant-advanced NSCLC. Patients who failed from first-line EGFR-TKIs and did not harbor T790M mutation were enrolled. Toripalimab plus carboplatin and pemetrexed were administrated every three weeks for up to six cycles, followed by the maintenance of toripalimab and pemetrexed. The primary endpoint was objective-response rate (ORR). Integrated biomarker analysis of PD-L1 expression, tumor mutational burden (TMB), CD8 + tumor-infiltrating lymphocyte (TIL) density, whole-exome, and transcriptome sequencing on tumor biopsies were also conducted. Forty patients were enrolled with an overall ORR of 50.0% and disease-control rate (DCR) of 87.5%. The median progression free survival (PFS) and overall survival were 7.0 and 23.5 months, respectively. The most common treatment-related adverse effects were leukopenia, neutropenia, anemia, ALT/AST elevation, and nausea. Biomarker analysis showed that none of PD-L1 expression, TMB level, and CD8 + TIL density could serve as a predictive biomarker. Integrated analysis of whole-exome and transcriptome sequencing data revealed that patients with DSPP mutation had a decreased M2 macrophage infiltration and associated with longer PFS than those of wild type. Toripalimab plus chemotherapy showed a promising anti-tumor activity with acceptable safety profiles as the second-line setting in patients with EGFR-mutant NSCLC. DSPP mutation might serve as a potential biomarker for this combination. A phase-III trial to compare toripalimab versus placebo in combination with chemotherapy in this setting is ongoing (NCT03924050).

ObjectiveThis study aimed to investigate the clinical spectra and outcomes in pregnancy-related optic neuritis (ON).MethodsWe analyzed the clinical subtype and prognosis of women with pregnancy-related ON in the neuro-ophthalmology department of the First Medical Center at the Chinese PLA General Hospital from January 2014 to December 2019.ResultsA total of 54 patients, including 21 (38.9%) with idiopathic ON (ION), 27 (50.0%) with aquaporin-4 (AQP4)-ON, and 6 (11.6%) with myelin oligodendrocyte glycoprotein (MOG)-ON, who experienced 58 informative pregnancies and 67 episodes of pregnancy-related ON were assessed. Among the ON attacks, there were 11 (16.4%) during pregnancy and 56 (83.6%) within 1 year postpartum (PP1) or after abortion, including 33 (49.3%) in the first trimester. In total, 14 (25.9%) patients with ON onset before pregnancy had a higher relapse rate during PP1 than within 1 year before pregnancy (p = 0.021), and 24 (85.7%) eyes with ION and nine (100%) with MOG-ON had significantly better visual outcomes (p ≥ 0.5) than those with AQP4-ON (14, 35%) (p < 0.001 and p < 0.001, respectively). Two AQP4-ON patients had premature birth and low baby weight, respectively. There were no birth defects or stillbirths.ConclusionThe significantly increased relapse rate and numerous cases of ON after pregnancy suggest that delivery adversely affects the course of ON.

Multidrug resistance (MDR) mediated by ATP binding cassette subfamily B member 1 (ABCB1) is significantly hindering effective cancer chemotherapy. However, currently, no ABCB1-inhibitory drugs have been approved to treat MDR cancer clinically, mainly due to the inhibitor specificity, toxicity, and drug interactions. Here, we reported that three polyoxypregnanes (POPs) as the most abundant constituents of Marsdenia tenacissima (M. tenacissima) were novel ABCB1-modulatory pro-drugs, which underwent intestinal microbiota-mediated biotransformation in vivo to generate active metabolites. The metabolites at non-toxic concentrations restored chemosensitivity in ABCB1-overexpressing cancer cells via inhibiting ABCB1 efflux activity without changing ABCB1 protein expression, which were further identified as specific non-competitive inhibitors of ABCB1 showing multiple binding sites within ABCB1 drug cavity. These POPs did not exhibit ABCB1/drug metabolizing enzymes interplay, and their repeated administration generated predictable pharmacokinetic interaction with paclitaxel without obvious toxicity in vivo. We further showed that these POPs enhanced the accumulation of paclitaxel in tumors and overcame ABCB1-mediated chemoresistance. The results suggested that these POPs had the potential to be developed as safe, potent, and specific pro-drugs to reverse ABCB1-mediated MDR. Our work also provided scientific evidence for the use of M. tenacissima in combinational chemotherapy.

Abstract Background The expansion of GGC repeat in the 5' untranslated region of the NOTCH2NLC has been associated with various neurogenerative disorders of the central nervous system and, more recently, oculopharyngodistal myopathy. This study aimed to report patients with distal weakness with both neuropathic and myopathic features on electrophysiology and pathology who present GGC repeat expansions in the NOTCH2NLC. Methods Whole‐exome sequencing (WES) and long‐read sequencing were implemented to identify the candidate genes. In addition, the available clinical data and the pathological changes associated with peripheral nerve and muscle biopsies were reviewed and studied. Results We identified and validated GGC repeat expansions of NOTCH2NLC in three unrelated patients who presented with progressive weakness predominantly affecting distal lower limb muscles, following negative results in an initial WES. We found intranuclear inclusions with multiple proteins deposits in the nuclei of both myofibers and Schwann cells. The clinical features of these patients are compatible with the diagnosis of distal motor neuropathy and rimmed vacuolar myopathy. Interpretation These phenotypes enrich the class of features associated with NOTCH2NLC‐related repeat expansion disorders (NRED), and provide further evidence that the neurological symptoms of NRED include not only brain, spinal cord, and peripheral nerves damage, but also myopathy, and that overlapping symptoms might exist.

SARS-CoV-2 3CL protease (3CLpro) is essential for coronavirus replication and of great interest as an antiviral drug target. Here, the authors show that the naturally occurring flavonoid myricetin is a non-peptidomimetic and covalent inhibitor of 3CLpro, and they solve crystal structures of 3CLpro with myricetin and derivatives, which reveal that the pyrogallol group covalently modifies the catalytic cysteine.

Abstract Objective We aimed to summarize the clinical, genetic, and myopathological features of a cohort of Chinese patients with congenital myasthenic syndrome, and follow up on therapeutic outcomes. Methods The clinical spectrum, mutational frequency of genes, and pathological diagnostic clues of various subtypes of patients with congenital myasthenic syndrome were summarized. Therapeutic effects were followed up. Results Thirty‐five patients from 29 families were recruited. Ten genes were identified: GFPT1 (27.6%), AGRN (17.2%), CHRNE (17.2%), COLQ (13.8%), GMPPB (6.9%), CHAT, CHRNA1, DOK7, COG7, and SLC25A1 (3.4% each, respectively). Sole limb‐girdle weakness was found in patients with AGRN (1/8) and GFPT1 (7/8) mutations, whereas distal weakness was all observed in patients with AGRN (6/8) mutations. Tubular aggregates were only found in patients with GFPT1 mutations (5/6). The patients with GMPPB mutations (2/2) had decreased alpha‐dystroglycan. Acetylcholinesterase inhibitor therapy resulted in no response or worsened symptoms in patients with COLQ mutations, a diverse response in patients with AGRN mutations, and a good response in patients with other subtypes. Albuterol therapy was effective or harmless in most subtypes. Therapy effects became attenuated with long‐term use in patients with COLQ or AGRN mutations. Interpretation The genetic distribution of congenital myasthenic syndrome in China is distinct from that of other ethnic origins. The appearance of distal weakness, selective limb‐girdle myasthenic syndrome, tubular aggregates, and decreased alpha‐dystroglycan were indicative of the specific subtypes. Based on the follow‐up findings, we suggest cautious evaluation of the long‐term efficacy of therapeutic agents in congenital myasthenic syndrome.

Due to the lack of effective supervision, guidance, training mechanism, there are serious problems in daylighting, energy efficiency, and thermal comfort of the existing rural residences in cold climate zone, China. In this paper, the multi-objective optimization was introduced to study the shape, size and constructure of the transparent building envelope of rural residences in cold climate zone, China. It began with the field investigation and the establishment of the prototypical models. Then the daylighting, heating and cooling load and thermal comfort of the building were simulated, and the multi-objective optimization was performed. The results indicated that the multi-objective optimization of the transparent building envelope could significantly improve daylighting, energy efficiency, and thermal comfort performance of the rural residences. The best values of the northward, the westward and the southward window-to-wall ratio are 0.10, 0.11, 0.12 respectively for the no-sunspace model, and that is 0.13, 0.13, 0.43 respectively for the sunspace model. Compared with the prototypical models, the useful daylight illuminances for the optimal no-sunspace model and sunspace model increased by 6% and 17% respectively, the heating and cooling load decreased by 23% and 17% respectively, and the predicted percentage of dissatisfied decreased by 12% and 9% respectively.

Abstract Mesenchymal stem cells (MSCs), due to their tumor tropism, are strongly recruited by various solid tumors and mobilized by inflammatory signals in the tumor microenvironment. However, effective cellular uptake is critical for MSC‐based drug delivery. In this study, we synthesized a spherical copolymer, polyethylenimine–poly(ε‐caprolactone), with aggregation‐induced emission (AIE) material and the anticancer drug, paclitaxel, coloaded onto its inner core. This was followed by the addition of a transactivator of transcription (TAT) peptide, a type of cell‐penetrating peptide, to modify the nanoparticles (NPs). Finally, the MSCs were employed to carry the TAT‐modified AIE‐NPs drug to the tumor sites and assist in simultaneous cancer diagnosis and targeted tumor therapy. In vitro, the TAT‐modified AIE‐NPs showed good biocompatibility, targeting, and stability in an aqueous solution besides high drug‐loading and encapsulation efficiency. In vitro, the AIE‐NPs exhibited a controllable release under a mildly acidic environment. The in vivo and in vitro studies showed high antitumor efficacy and low cytotoxicity of the AIE‐NP drug, whereas biodistribution confirmed the tumor tropism of MSCs. To summarize, the MSC‐based AIE‐NP drugs loaded with TAT possessed good biocompatibility and high antitumor efficacy via the enhanced NP‐drug uptake. In addition, the tumor tropism of MSCs provided selective drug uptake by the tumor cells and thus reduced the systemic side effects.

Abstract Background The surgical treatment of acetabular fracture has adverse outcomes and high risk, and minimally invasive method is a good way to reduce complications and improve hip joint function. This study is to investigate the treatment of certain acetabular fractures primarily involving the anterior column and quadrilateral plate using a limited pararectus approach and the anatomical plates. Methods A consecutive cohort of 17 patients with anterior displaced acetabular fractures were managed operatively with a limited approach and the anatomical plates. Ten patients had anterior column fractures, 1 patient had anterior wall fracture, 4 patients had transverse fractures and 2 patients had anterior column with posterior hemi-transverse fractures. The inferior half of the pararectus approach was adopted to open the medial window and to access the anterior column and the quadrilateral plate. The anatomical plates were used for internal fixation. Residual displacements were assessed on the postoperative CT scans using a standardized digital method. The surgical details, hip functional outcomes, and complications were noted. Results All of the patients were operated using the limited pararectus approach and the anatomical plates successfully. The mean operative time and blood loss were 90.9 min and 334.1 ml, respectively. The average postoperative residual gap and step displacement on CT were 2.9 mm and 0.7 mm, respectively. The radiological outcome was estimated according to the Matta score, ten of the cases were graded anatomical, six were graded imperfect, and one was graded poor. Follow up averaged 15 months. Functional outcomes were excellent for nine, good for six, and fair for two. It was noted that one case of peritoneal injury was repaired intraoperatively. Conclusions The limited pararectus approach with the advantages of less trauma, direct exposure to the anterior column and quadrilateral plate. The anatomical plates can fit with the surface of the acetabulum, which saves the time of remodeling plates during operation and facilitate fracture reduction. The combination approach can be a good choice for limited surgery of displaced anterior acetabular fractures especially involving the quadrilateral plate.

Remote sensing monitoring of glacial lakes is an indispensable tool for identifying and preventing glacial lake disasters. At present, the existing extraction methods of glacial lakes based on Landsat remote sensing image have achieved remarkable results, but the algorithms used lack the ability to analyze glacial lake spectral and shape and texture features, and require manual design parameters to fine tune the automation of the algorithm. As a result, it cannot mine the depth features of glacier lakes in remote sensing images accurately enough. To address these challenges, this study designed a self-attention mechanism module U-net network that enhances the propagation of features, reduces information loss, strengthens the weight of glacial lake areas, restrains the weight of irrelevant features, reduces the influence of low image contrast on the model, and deals with the variety of pixel categories in glacial lakes. These features improve the performance of the model. Based on Landsat-8 images, we first extracted glacial lakes in large-scale alpine areas using a U-net network model. To make it a self-attention U-net network, we introduced the attention mechanism into the step connection part of the U-net network to adjust feature weight, focus on learning glacial lake features, and strengthen the network to extract the glacial lake features. Finally, we selected the combination of bands 3, 5, and 6 and all bands of Landsat-8 images sing the self-attention U-net network to extract glacial lakes in the study area and compared and analyzed the extraction results. The experimental results and analyses revealed that the proposed method can effectively segment glacial lakes from Landsat-8 remote sensing images. Its effectiveness was proven by different evaluation indices. Compared with a standard U-net network, the true positive for the combination of 3, 5, and 6 bands increased by 15.95% and for all bands by 5.79%. The area under curve for the whole study area reached 85.03% for all bands. The improved U-net network can, thus, meet the real time needs of glacial lake disaster information acquisition.

One of the largest families of transcription factors in plants, the MYB transcription factors family (Myeloblastosis, MYB TF), plays a vital role in regulating plant biochemical and physiological processes. The role of MYB TF in coping with stresses, such as drought, salt and cold, has been reported. Unfortunately, a comprehensive identification of R2R3-MYB TF in Masson pine (Pinus massoniana) has not been achieved. In this study, a total of 49 sequences were identified as R2R3-MYB TF. The structure, function and phylogenetic relationships of the conserved structural domains of Masson pine R2R3-MYB TF and Populus trichocarpa Torr. & A.Gray ex Hook. TFs were compared using bioinformatics tools. The results showed that Masson pine R2R3-MYB TF was divided into 24 groups, mainly located in the nucleus, and mostly lacking signal peptides and transmembrane structural domains with multiple phosphorylation sites. The drought stress-responsive R2R3-MYB gene, PmMYB4, was selected from the drought stress transcriptome based on analysis of the expression pattern and tissue specificity of PmMYB4 gene under abiotic stress using qPCR. The results showed that PmMYB4 can be involved in drought stress treatment through ABA signaling, as well as in multiple stress responses such as salt stress, and there were significant differences in the expression of PmMYB4 in the eight tissues. These results provide a reference scheme for the functional identification of R2R3-MYB transcription factors, which may be involved in plant responses to multiple stresses such as drought, and enrich our understanding of the functions of R2R3-MYB transcription factors in plants.

Basic leucine zipper (bZIP) transcription factors (TFs) are ubiquitous in eukaryotes. Members of this family play significant roles in the regulation of plant growth, signal transduction, and various stresses. To date, bZIP TFs have been extensively studied in various plants, but there is little information about them in Pinus massoniana Lamb. In this study, 55 bZIP TFs were identified based on data from four different P. massoniana transcriptomes, and a systematic analysis was performed. According to the phylogenetic results, P. massoniana bZIP TFs were divided into 11 groups. Each bZIP protein contained a highly conserved bZIP domain, and the numbers and types of motifs were similar in the same group. The PmbZIPs were nuclear localization proteins. Based on the pine wood nematode inoculation transcriptome, the transcriptional profiles revealed that 25 PmbZIP genes could respond to pine wood nematodes at different levels. Genes PmbZIP3, PmbZIP4, PmbZIP8, PmbZIP20, and PmbZIP23 were selected to be upregulated in the process of inoculation with pine wood nematodes. These five genes had different expression levels in different tissues and were responsive to the related treatment conditions. Transcriptional activity analysis showed that PmbZIP3 and PmbZIP8 were transcriptional activators; PmbZIP4, PmbZIP20 and PmbZIP23 were transcriptional repressors. These findings provide preliminary information on PmbZIP TFs, which is helpful for further study of other physiological functions of bZIP TFs in P. massoniana.