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Abstract Background A combination of prone positioning (PP) and venovenous extracorporeal membrane oxygenation (VV-ECMO) is safe, feasible, and associated with potentially improved survival for severe acute respiratory distress syndrome (ARDS). However, whether ARDS patients, especially non-COVID-19 patients, placed in PP before VV-ECMO should continue PP after a VV-ECMO connection is unknown. This study aimed to test the hypothesis that early use of PP during VV-ECMO could increase the proportion of patients successfully weaned from ECMO support in severe ARDS patients who received PP before ECMO. Methods In this prospective observational study, patients with severe ARDS who were treated with VV-ECMO were divided into two groups: the prone group and the supine group, based on whether early PP was combined with VV-ECMO. The proportion of patients successfully weaned from VV-ECMO and 60-day mortality were analyzed before and after propensity score matching. Results A total of 165 patients were enrolled, 50 in the prone and 115 in the supine group. Thirty-two (64%) and 61 (53%) patients were successfully weaned from ECMO in the prone and the supine groups, respectively. The proportion of patients successfully weaned from VV-ECMO in the prone group tended to be higher, albeit not statistically significant. During PP, there was a significant increase in partial pressure of arterial oxygen (PaO2) without a change in ventilator or ECMO settings. Tidal impedance shifted significantly to the dorsal region, and lung ultrasound scores significantly decreased in the anterior and posterior regions. Forty-five propensity score-matched patients were included in each group. In this matched sample, the prone group had a higher proportion of patients successfully weaned from VV-ECMO (64.4% vs. 42.2%; P = 0.035) and lower 60-day mortality (37.8% vs. 60.0%; P = 0.035). Conclusions Patients with severe ARDS placed in PP before VV-ECMO should continue PP after VV-ECMO support. This approach could increase the probability of successful weaning from VV-ECMO. Trial Registration ClinicalTrials.Gov: NCT04139733. Registered 23 October 2019.

Abstract Despite advancements in antiretroviral therapy (ART) suppressing HIV-1 replication, existing antiviral drugs pose limitations, including lifelong medication, frequent administration, side effects and viral resistance, necessitating novel HIV-1 treatment approaches. CD4, pivotal for HIV-1 entry, poses challenges for drug development due to neutralization and cytotoxicity concerns. Nevertheless, Ibalizumab, the sole approved CD4-specific antibody for HIV-1 treatment, reignites interest in exploring alternative anti-HIV targets, emphasizing CD4’s potential value for effective drug development. Here, we explore anti-CD4 nanobodies, particularly Nb457 from a CD4-immunized alpaca. Nb457 displays high potency and broad-spectrum activity against HIV-1, surpassing Ibalizumab’s efficacy. Strikingly, engineered trimeric Nb457 nanobodies achieve complete inhibition against live HIV-1, outperforming Ibalizumab and parental Nb457. Structural analysis unveils Nb457-induced CD4 conformational changes impeding viral entry. Notably, Nb457 demonstrates therapeutic efficacy in humanized female mouse models. Our findings highlight anti-CD4 nanobodies as promising HIV-1 therapeutics, with potential implications for advancing clinical treatment against this global health challenge.

Abstract Background The mortality rate and prognosis of short-term and long-term acute kidney injury (AKI) patients who undergo continuous renal replacement therapy (CRRT) are different. Setting up risk stratification tools for both short-term and long-term deaths is highly important for clinicians. Method A total of 1535 AKI patients receiving CRRT were included in this study, with 1144 from the training set (the Dryad database) and 391 from the validation set (MIMIC IV database). A model for predicting mortality within 10 and 90 days was built using nine different machine learning (ML) algorithms. AUROC, F1-score, accuracy, sensitivity, specificity, precision, and calibration curves were used to assess the predictive performance of various ML models. Results A total of 420 (31.1%) deaths occurred within 10 days, and 1080 (68.8%) deaths occurred within 90 days. The random forest (RF) model performed best in both predicting 10-day (AUROC: 0.80, 95% CI: 0.74–0.84; accuracy: 0.72, 95% CI: 0.67–0.76; F1-score: 0.59) and 90-day mortality (AUROC: 0.78, 95% CI: 0.73–0.83; accuracy: 0.73, 95% CI: 0.69–0.78; F1-score: 0.80). The importance of the feature shows that SOFA scores are rated as the most important risk factor for both 10-day and 90-day mortality. Conclusion Our study, utilizing multiple machine learning models, estimates the risk of short-term and long-term mortality among AKI patients who commence CRRT. The results demonstrated that the prognostic factors for short-term and long-term mortality are different. The RF model has the best prediction performance and has valuable potential for clinical application.

Abstract Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO2) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1β and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.

As dust source bare soil land (BSL) contributes to air pollution and affects the photosynthesis of green plants and carbon absorption, it is the objective of this study to develop an approach for monitoring the changes of BSL using remote sensing technology. Unlike other land use/cover types, the classification of BSL as well as its change detection is often ignored. For traditional convolutional neural networks, deep layers cause a long range between input and output, inevitably leading to the loss of information and computational costs. To alleviate this problem, transformer is available to model the global dependencies. Bitemporal association, which is described as subtraction or attention mechanism, is not fully considered by current methods. Therefore, we proposed a spatial-temporal association enhanced mobile-friendly vision transformer (STAE-MobileVIT) for change detection of high-resolution images with light weight and high efficiency. On the one hand, a temporal association enhanced MobileVIT block is employed to strengthen the association of bitemporal images during feature extraction. On the other hand, a multiscale feature difference aggregator enhanced by spatial association is designed to fuse semantic and detailed information. Since the lack of binary change detection dataset for BSL, we established a small dataset named BSL-CD, consisting of 1083 pairs of 0.8 m bitemporal images with the size of 256 × 256 pixels, along with the corresponding labels. The experiments on BSL-CD show that our light-weight model surpass seven common methods by 3.48, 5.05, and 1.44 percent on F1, IoU, and OA, which proves the efficiency and accuracy of STAE-MobileVIT.

Berry fruits produced by Vaccinium (Ericaceae) plants are small but have a signature flavor and have become increasingly popular in the 21st century. However, self-incompatibility (SI) results in a relatively low fruit-set ratio and reduced fruit quality in Vaccinium. In this study, using Vaccinium ashei (V. ashei) styles after cross-pollination (CP) and self-pollination (SP) as material, transcriptomics and gene expression analyses were performed using high-throughput RNA sequencing and quantitative real-time polymerase chain reaction (qRT-PCR). Subsequently, evolutionary analysis and conserved sequences analysis of candidate genes were conducted. Among the 135,324 unigenes, 30,863 were shown to be differentially expressed, and eight randomly selected differentially expressed genes were expressed in the styles at 96 hours after SP and CP. The transcriptomics and qRT-PCR results were significantly correlated, which confirmed the reliability of the differentially expressed genes obtained in our study. Compared with SP96, six differentially expressed ribonuclease T2 family genes were obtained in CP96, which were considered candidates for S-RNase. Additionally, the spatiotemporal and organizational expression trends of six candidates for S-RNase were confirmed by qRT-PCR, and the evolutionary and conservative sequence analysis indicated six candidate S-RNases with the typical S-RNase structure. The spatiotemporal and organizational expression results and evolutionary and conservative sequence analyses of the six candidate S-RNases suggest that SI in V. ashei is likely an S-RNase-mediated gametophytic one. This finding suggests the involvement of novel, previously undiscovered components involved in the V. ashei SI system. These findings help elucidate the molecular mechanisms of SI in rabbiteye blueberry and may also benefit breeding, production, and genomics research in V. ashei and other Vaccinium species.

Introduction: Ultraviolet (UV) radiation is believed to play a significant role in accelerating litter decomposition in water-limited ecosystems. Litter traits also influence the decomposition. However, the dominance of litter traits and ultraviolet radiation on litter decomposition in hyper-arid deserts (annual precipitation: potential evaporation < 0.05) with diverse species and seasonal variations remain unclear.Methods: To address this knowledge gap, we examined the decomposition of three dominant litter species (Karelinia caspia, Alhagi sparsifolia, and Populus euphratica) in the southern edge of the Taklimakan Desert, Northwest China.Results: Our results revealed that under UV radiation conditions, K. caspia, A. sparsifolia, and P. euphratica experienced mass losses of 45.4%, 39.8%, and 34.9%, respectively, and 20%, 22.2% and 17.4%, respectively under UV filtering treatment. Specifically, the loss rate of carbon and lignin under UV radiation, was 2.5 and 2.2 times higher than under UV filtering treatment, respectively.Conclusion: UV radiation did not dominate decomposition throughout the year in our study area, and the loss rate of litter traits was significantly higher in summer than in winter under UV radiation. Moreover, this photodegradation is related to the intensity of UV exposure, but not to precipitation or temperature. Surprisingly, species type had no significant effect on litter decomposition. However, when we applied a UV filtering treatment, we observed higher loss rates of nitrogen compared with the ambient treatment, suggesting the involvement of other spectra in the litter decomposition process. Overall, our findings elucidate that UV radiation is a crucial factor that affects litter mass loss. The magnitude of this effect mostly varies with the season rather than the species of litter.

Intercropping has the potential to enhance yields and nutrient availability in resource-limited agricultural systems. However, the effects on crop yield nutrients and soil properties can vary considerably depending on the specific plant combinations and intercropping ratios used. In this study, the advantages and impacts of intercropping C. esculentus with legumes were investigated by measuring their biomass, nutrient content, and soil properties. The experiment included five intercropping treatments: monoculture of C. esculentus (MC), intercropping of C. esculentus with Medicago sativa L. (alfalfa) at row spacing ratios of 4:4 (4:4CM) and 8:4 (8:4CM), and intercropping of C. esculentus with Glycine max (L.) Merr. (soybean), also at row spacing ratios of 4:4 (4:4CG) and 8:4 (8:4CG). Our results demonstrated that all four intercropping treatments (4:4CM, 4:4CG, 8:4CM, and 8:4CG) significantly increased the biomass of C. esculentus by approximately 41.05%, 41.73%, 16.08%, and 18.43%, respectively, compared with monoculture cultivation alone, among which the 4:4CG treatment was optimum. However, no significant differences were observed in alfalfa or soybean biomass across different intercropping ratios. A notable increase was found in the total nitrogen (TN) and total phosphorus (TP) contents in the leaves, roots, and tubers of C. esculentus under intercropping, along with increased soil organic carbon (SOC), alkaline-hydrolyzed nitrogen (AN), available phosphorus (AP), microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), and soil water content (SWC), and significantly reduced the soil pH. Among the intercropping treatments, the 4:4CG treatment also exhibited the most favorable soil properties. In particular, compared with MC, the 4:4CG treatment resulted in significant increases of 163.8%, 394.6%, and 716.8% in SOC, AN, and AP contents, respectively. The same treatment also led to significant increases of 48.34%, 46.40%, and 208.65% in MBC, MBN, and SWC, respectively. Overall, the findings suggest that the use of 4:4CG intercropping is an effective approach for sustainable farming management in Xinjiang.

Against the backdrop of global climate warming, the issue of flash flood disasters in small watersheds triggered by heavy rainfall is gradually becoming more prominent. Selecting an appropriate hydrological model is crucial for flash flood disaster defense. This article focuses on the Daxi Water Basin in Lianping County, Guangdong Province, as the research area. Firstly, organize the data and subject it to standardization processing. Subsequently, establish the topological relationships within the basin, construct a hydrological model for simulating flood processes in Chinese mountainous regions, and obtain a set of model parameters applicable to the specific basin. The results indicated that: ① the relative errors of flood runoff depth were all less than 7%, with an average of 4.5%; ② the relative errors of peak flow for all events were less than 6%, with an average of 4.2%; ③ peak time errors were all within ±2 h, either earlier or later than the actual peak by 1 h; ④ the Nash-Sutcliffe efficiency coefficient for floods were all greater than 0.8, with an average of 0.86. The research results above will serve as a reference and guidance for flood defense management in the Daxi Water Basin.

Abstract Background Xp22.31 deletion and duplication have been described in various studies, but different laboratories interpret pathogenicity differently. Objectives Our study aimed to refine the genotype–phenotype associations between Xp22.31 copy number variants in fetuses, with the aim of providing data support to genetic counseling. Methods We retrospectively analyzed karyotyping and single nucleotide polymorphism array results from 87 fetuses and their family members. Phenotypic data were obtained through follow-up visits. Results The percentage of fetuses carrying the Xp22.31 deletions (9 females, 12 males) was 24.1% (n = 21), while duplications (38 females, 28 males) accounted for 75.9% (n = 66). Here, we noted that the typical region (from 6.4 to 8.1 Mb, hg19) was detected in the highest ratio, either in the fetuses with deletions (76.2%, 16 of 21) or duplications (69.7%, 46 of 66). In female deletion carriers, termination of pregnancy was chosen for two fetuses, and the remaining seven were born without distinct phenotypic abnormalities. In male deletion carriers, termination of pregnancy was chosen for four fetuses, and the remaining eight of them displayed ichthyosis without neurodevelopmental anomalies. In two of these cases, the chromosomal imbalance was inherited from the maternal grandfathers, who also only had ichthyosis phenotypes. Among the 66 duplication carriers, two cases were lost at follow-up, and pregnancy was terminated for eight cases. There were no other clinical findings in the rest of the 56 fetuses, including two with Xp22.31 tetrasomy, for either male or female carriers. Conclusion Our observations provide support for genetic counseling in male and female carriers of Xp22.31 copy number variants. Most of them are asymptomatic in male deletion carriers, except for skin findings. Our study is consistent with the view that the Xp22.31 duplication may be a benign variant in both sexes.

Soil salinization threatening natural and agricultural production challenges global food security. Halophytes are of great interest in soil desalinization in recent years; yet, there is a lack of a comprehensive quantitative overview of biotic and abiotic factors for halophytes’ desalinization performance across global scales. Here, a meta-analysis was conducted using 400 observations from 53 peer-reviewed studies to assess desalinization by halophytes in relation to 27 variables. Results showed that soil salinity was significantly decreased in halophytes field on average by 37.7% compared to control on a global scale (p < 0.05). Desalinization performance was better in cold and hot regions than in temperate regions, in dry regions than in wet regions, in alkaline saline soils than in neutral saline soils, and in conditions with low sand content than high sand content. Under aboveground harvest treatment, desalinization increased with the years of cultivation, while no trends were detected under no harvest treatment, indicating the importance of aboveground accumulation. Desalinization was not related to soil CaCO3 content but was accompanied by soil structure improvement, nutrition enrichment, and microbe propagation, implying other root-microbe-soil interactions rather than CaCO3 dissolution play important roles. Shoot biomass could be used as an indicator of the desalinization performance, and the performance would not be decreased due to the high uptake selectivity for K+ over Na+. Notably, desalinization was similar in the pot experiments and field experiments, but pot experiments would magnify the contribution of aboveground salt accumulation to desalinization. Our findings can help to expand the applicability and efficiency of halophytes for sustainable agricultural development in saline soils.

The progression of oesophageal squamous cell carcinoma (ESCC) from early to advanced stages requires comprehensive molecular characterisation. Here, the authors perform a proteogenomics analysis of ESCC patient samples across nine histopathological stages and three phases, identifying key alterations and paths for progression.

Oocytes are efficient at reprogramming terminally differentiated cells to a totipotent state. Nuclear transfer techniques can exploit this property to produce cloned animals. However, the overall efficiency is low. The use of umbilical cord mesenchymal stem cells (UC-MSCs) as donor nuclei may increase blastocyst rates, but the exact reasons for this remain unexplored. A single-cell transcriptomic approach was used to map the transcriptome profiles of eight-cell embryos that were in vitro-fertilized and handmade-cloned using umbilical cord mesenchymal stem cells and fibroblasts as nuclear donors. Differences were examined at the chromatin level, the level of differentially expressed genes, the level of histone modifications and the level of DNA methylation. This research provides critical information regarding the use of UC-MSCs as a preferred donor nucleus for nuclear transfer techniques. It also offers unique insights into the mechanism of cellular reprogramming.

Afatinib, as the first-line treatment for non-small cell lung cancer (NSCLC), causes severe gastrointestinal adverse reactions that greatly affect patients' quality of life and even potentially result in treatment discontinuation. Multiple dose adjustments and concomitant use of anti-diarrheal medications are commonly employed to manage diarrhea, also allowing for a recovery period between each adjustment. However, these approaches are based on empirical guidance and still have limitations. This study aims to explore reliable approaches to alleviate diarrhea by focusing on two strategies: adjusting the dosing regimen of afatinib itself and implementing combination therapy. In this study, we firstly revealed a dose-dependent relationship between afatinib-induced diarrhea and gastrointestinal epithelial damage, resulting in atrophy, reduced expression of tight junction proteins, and increased permeability. We further found that even after discontinuation of the medication, although the severity of diarrhea had improved to baseline, the tight junction proteins and permeability of the intestinal epithelium did not fully recover, and the pharmacokinetics studies showed that drug absorption significantly increased than normal. This indicated the recovery period was longer than expected and may accelerate the occurrence of subsequent episodes of diarrhea. Hence, it would be prudent to consider adjustments to the starting dose or the recovery interval. Furthermore, we initially investigated the relationship between DPP enzyme and afatinib-induced diarrhea and found a significant decrease in plasma DPP enzyme activity following afatinib-induced diarrhea. Subsequently, we conducted continuous treatment with sitagliptin and observed significant improvement in afatinib-induced diarrhea. We observed that sitagliptin can promote the production of anti-inflammatory factors, increase the expression of intestinal epithelial tight junction proteins, and improve intestinal microbiota, further validating the mechanism through the use of GLP-23-33 as GLP-2 receptor inhibitor. In conclusion, sitagliptin exhibits promising potential as a therapeutic option for managing afatinib-induced diarrhea. Taken together, our study provides valuable insights into alleviating afatinib-induced diarrhea through both afatinib medication adjustment and sitagliptin combination therapy.

IntroductionSolar radiation plays a crucial role in the decomposition of litter and the cycling of nutrients. Previous studies have investigated that the net effect of solar radiation on litter decomposition depends on the balance of its facilitative and inhibitory effects on microbial activity; however, a gap in understanding the mechanism by which precipitation affects the net effect of solar radiation and the mechanism of litter decomposition on a global scale was observed.MethodsIn addressing this gap, a comprehensive meta-analysis of 351 data points from 37 published studies was conducted to estimate the sole radiation effect and interactive effect of solar radiation and precipitation on a global scale, as well as how they vary at different precipitation levels. In addition, the importance of influential factors regulating the net effect of solar radiation on litter decomposition was assessed to identify the key drivers of the response of mass loss to solar radiation at different precipitation levels.ResultsOur findings indicated that solar radiation largely regulates litter decomposition, and the direction and magnitude are potentially dependent on the precipitation regime. In addition, solar radiation significantly increased mass loss and decreased the nutrient remaining. Furthermore, the effects of solar radiation on mass loss, C remaining, and N remaining were found to be similar among areas with precipitation levels below 200 and above 800 mm and greater than in areas with precipitation levels between 200-400 mm and 400-800 mm. The effect of solar radiation on CO2 emissions varied from 13.97% when precipitation was below 200 mm to −0.707% when precipitation was between 200 and 400 mm.ConclusionClimatic factors determine the response ratio of mass loss to solar radiation in arid lands, whereas the initial litter characteristics have a great influence on the response of mass loss to solar radiation in ecosystems that are not moisture limited. The effect of precipitation on the photodegradation mechanism of litter was primarily achieved by influencing the decomposition of lignin, and the main effect of solar radiation on litter decomposition will shift from the positive effect of “photopriming” to the negative effect of “microbial inhibition” with the increase of precipitation. Our findings can provide a comprehensive understanding of litter decomposition patterns on a global scale, and our results showed that CO2 emissions from photodegradation will be lessened by precipitation, which is important in predicting CO2 emission and separating sources of CO2 under future increasing precipitation scenarios, particularly in arid lands.

Abstract Background To understand the trend of equalization in maternal services and to guide policy-makers regarding resource allocation and public health policy in China. Methods Twelve indicators, including maternal services needs, utilization, and resource allocation, were collected from China Health Statistical Year Book 2010 and 2020. WHO’s comprehensive evaluation model and the non-integral Rank Sum Ratio (RSR) method were used to analyze, rank, and categorize maternal services of 31 provinces (cities, autonomous regions) in China. Results All provinces (cities, autonomous regions) are grouped into relative balance areas, low input areas, resource shortage areas, overutilization areas, and resource waste areas. In 2019, there were 18 provinces (cities, autonomous regions) in the relative balanced area, and more than one-half had achieved equal development. Compared to 2009, the resource shortage area decreased from three to zero, and the resource waste area increased from four to six. Among the provinces (cities, autonomous regions) with a type change compared with 2009, eight changed to a relative balance areas, and four showed an improvement. Conclusion Under the policy guidance of promoting the equalization of public health services, maternal services are gradually realized. However, several provinces (cities, autonomous regions) still have problems such as the mismatch between resource input and health needs, resource waste, over-utilization, etc. Therefore, specific policies should be formulated according to the actual types to promote the transformation into equalization regions.

The mechanisms of resistance to therapy in gastric cancer remain to be explored. Here, proteomic profiling of 206 tumour tissues from patients treated with chemotherapy and anti-HER2-based therapy results in the identification of four molecular subtypes and the development of prognostic models.

IntroductionWith the extensive use of immunosuppressants, immunosuppression-associated pneumonitis including Pneumocystis jirovecii pneumonia (PCP) has received increasing attention. Though aberrant adaptive immunity has been considered as a key reason for opportunistic infections, the characteristics of innate immunity in these immunocompromised hosts remain unclear.MethodsIn this study, wild type C57BL/6 mice or dexamethasone-treated mice were injected with or without Pneumocystis. Bronchoalveolar lavage fluids (BALFs) were harvested for the multiplex cytokine and metabolomics analysis. The single-cell RNA sequencing (scRNA-seq) of indicated lung tissues or BALFs was performed to decipher the macrophages heterogeneity. Mice lung tissues were further analyzed via quantitative polymerase chain reaction (qPCR) or immunohistochemical staining.ResultsWe found that the secretion of both pro-inflammatory cytokines and metabolites in the Pneumocystis-infected mice are impaired by glucocorticoids. By scRNA-seq, we identified seven subpopulations of macrophages in mice lung tissues. Among them, a group of Mmp12+ macrophages is enriched in the immunocompetent mice with Pneumocystis infection. Pseudotime trajectory showed that these Mmp12+ macrophages are differentiated from Ly6c+ classical monocytes, and highly express pro-inflammatory cytokines elevated in BALFs of Pneumocystis-infected mice. In vitro, we confirmed that dexamethasone impairs the expression of Lif, Il1b, Il6 and Tnf, as well as the fungal killing capacity of alveolar macrophage (AM)-like cells. Moreover, in patients with PCP, we found a group of macrophages resembled the aforementioned Mmp12+ macrophages, and these macrophages are inhibited in the patient receiving glucocorticoid treatment. Additionally, dexamethasone simultaneously impaired the functional integrity of resident AMs and downregulated the level of lysophosphatidylcholine, leading to the suppressed antifungal capacities.ConclusionWe reported a group of Mmp12+ macrophages conferring protection during Pneumocystis infection, which can be dampened by glucocorticoids. This study provides multiple resources for understanding the heterogeneity and metabolic changes of innate immunity in immunocompromised hosts, and also suggests that the loss of Mmp12+ macrophages population contributes to the pathogenesis of immunosuppression-associated pneumonitis.

IntroductionMalonyl coenzyme A decarboxylase deficiency is caused by an abnormality in the MLYCD gene. The clinical manifestations of the disease involve multisystem and multiorgan.MethodsWe collected and analyzed a patient's clinical characteristics, genetic chain of evidence and RNA-seq. We use the search term “Malonyl-CoA Decarboxylase Deficiency” on Pubmed to collect cases reported.ResultsWe report a 3-year-old girl who is presented with developmental retardation, myocardial damage and elevated C3DC. High-throughput sequencing identified heterozygous mutation (c.798G>A, p.Q266?) in the patient inherited from her father. The other heterozygous mutation (c.641+5G>C) was found in the patient inherited from her mother. RNA-seq showed that there were 254 differential genes in this child, among which 153 genes were up-regulated and 101 genes were down-regulated. Exon jumping events occurred in exons encoding PRMT2 on the positive chain of chromosome 21, which led to abnormal splicing of PRMT2. (P

Abstract Background Former single center studies indicated that HER2 assessment with two primary tumor blocks (dual block HER2 assessment) could be an efficient and practical approach to overcome the adverse impact of heterogeneity and acquire a HER2 positive rate in gastric cancer (GC). This multicenter prospective clinical trial (NCT 02843412) was launched to verify its value and generality. Methods A total of 3806 participants with primary GCs have been enrolled from 8 hospitals in China. Two primary tumor blocks were selected and recorded as block 1 and block 2 after histological evaluation. An HER2 (4B5) rabbit monoclonal antibody was used for the immunohistochemistry (IHC) analysis. Results In total patients, HER2 IHC positive (3+) rate with dual block assessment (9.4%) was higher than that with single block assessment (block 1: 7.8%, block 2: 7.8%) (P

Abstract Background Gastric neoplasms with fundic gland differentiation include oxyntic gland adenomas (OGAs) and gastric adenocarcinomas of fundic gland type (GA-FGs). Due to their well-differentiated and similar morphology with normal fundic glands, it is usually challenging to identify these lesions in pathological diagnosis, especially in biopsy specimens. This study aims to explore and verify the potential role of a newly developed monoclonal antibody (McAb) NJ001 (SP70) in differentiating fundic neoplasms from non-neoplastic fundic gland lesions. Methods Twenty-three cases of histological confirmed gastric fundic gland neoplasms were obtained, including 12 cases of OGAs and 11 of GA-FGs. Fifty cases of fundic gland polyps (FGPs) were taken as the control group. Six cases of well-differentiated gastric neuroendocrine tumors (NETs) (easily misdiagnosed) were also obtained. Key clinicopathological information was collected. SP70 immunostaining was performed (with para-tumor normal fundic glands as internal control). The positive intensity and staining pattern of SP70 were analyzed and compared. Results In normal gastric mucosa, SP70 was strongly and diffusely stained on the cytoplasm in fundic glands, but not in the foveolar epithelium. Therefore, a zonal distribution of SP70 was observed in normal mucosa. FGPs (50/50, 100%) shared a similar expression pattern with normal fundic glands. In fundic gland neoplasms, a significant down-expression of SP70 was observed in both OGAs and GA-FGs. The positive rate of SP70 in fundic gland neoplasms (6/23, 26.1%) was significantly lower than that in FGPs (100%) (P0.05). In these 6 NET cases, SP70 was weak to moderate intensity in the majority of tumor cells (with a different expression pattern). Conclusion Down-expression of SP70 is a specific feature to fundic gland neoplasms including OGAs and GA-FGs. Therefore, SP70 can serve as a potential biomarker in the identification and differential diagnosis of fundic gland neoplasms.

IntroductionSoil microbial communities are key to functional processes in terrestrial ecosystems, and they serve as an important indicator of grasslands status. However, the responses of soil microbial communities and functional potential to drought stress in semiarid alpine grasslands remain unclear.MethodsHere, a field experiment was conducted under ambient precipitation as a control, −20% and −40% of precipitation to explore the responses of soil microbial diversity, community composition, and predicted functional potential to drought stress in a semiarid alpine grassland located in the northwest of China. Moreover, 16S rRNA gene and ITS sequencing were used to detect bacterial and fungal communities, and the PICRUST and FUNGuild databases were used to predict bacterial and fungal functional groups.ResultsResults showed drought stress substantially changes the community diversity of bacteria and fungi, among which the bacteria community is more sensitive to drought stress than fungi, indicating that the diversity or structure of soil bacteria community could serve as an indicator of alpine grasslands status. However, the fungal community still has difficulty maintaining resistance under excessive drought stress. Our paper also highlighted that soil moisture content, plant diversity (Shannon Wiener, Pieiou, and Simpson), and soil organic matter are the main drivers affecting soil bacterial and fungal community composition and predicted functional potential. Notably, the soil microbial functional potential could be predictable through taxonomic community profiles.ConclusionOur research provides insight for exploring the mechanisms of microbial community composition and functional response to climate change (longer drought) in a semiarid alpine grassland.

Background: Spatial transcriptome (ST) provides molecular profiles of tumor cells at the spatial level, which brings new progress to the research of tumors and the tumor microenvironment. This study summarizes the experiences and lessons learned in the spatial section preparation of two different pathological types of nose and skull base tumors at our institution, with the aim of offering guidelines to researchers to avoid wasting precious samples and provide a basis for the application of ST in clinical practice. Methods: Frozen tissue blocks from patients with squamous cell carcinoma and adenocarcinoma of the nose and skull base diagnosed at our institution were prepared. The effects of different procedures and pathological tissue types on slide quality were explored and evaluated using RNA integrity number (RIN) and HE scores as criteria. The effects of different RIN values on ST sequencing data were explored. Results: A total of 43 samples were obtained from 26 patients, including 22 with squamous carcinomas and 21 with adenocarcinomas. Thirteen samples with satisfactory RNA quality control and good histological morphology were sequenced for ST. Sample isolation time 7 in ST sequencing results was found, indicating that RIN ≥6 can be used as a criterion for qualified RNA quality control. Therefore, fresh tissues washed as soon as possible with cold PBS and then dried using OCT for snap freezing are currently the best method for preparing spatial sections of nose and skull base tumor tissues of different pathological types. Conclusion: This study is the first to investigate the feasibility of applying ST to different pathological types of nose and skull base tumors and to demonstrate the widespread application of ST in tumors. Rational optimization of spatial slide preparation procedures and exploration of individualized pre-sequencing protocols are used as the first stage to ensure the quality of spatial sequencing and lay the foundation for subsequent spatial analysis.

IntroductionThe productivity and community structures of terrestrial ecosystems are regulated by total precipitation amount and intra-annual precipitation patterns, which have been altered by climate change. The timing and sizes of precipitation events are the two key factors of intra-annual precipitation patterns and potentially drive ecosystem function by influencing soil moisture. However, the generalizable patterns of how intra-annual precipitation patterns affect the productivity and community structures of ecosystems remain unclear. MethodsWe synthesized 633 observations from 17 studies and conducted a global meta-analysis to investigate the influences of intra-annual precipitation patterns on the productivity and community structures of terrestrial ecosystems. By classifying intra-annual precipitation patterns, we also assess the importance of the magnitude and timing of precipitation events on plant productivity.ResultsOur results showed that the intra-annual precipitation patterns decreased diversity by 6.3% but increased belowground net primary productivity, richness, and relative abundance by 16.8%, 10.5%, and 45.0%, respectively. Notably, we found that the timing uniformity of precipitation events was more important for plant productivity, while the plant community structure benefited from the increased precipitation variability. In addition, the relationship between plant productivity and community structure and soil moisture dynamic response was more consistent with the nonlinear model.ComclusionsThe patterns of the responses of plant productivity and community structure to altered intra-annual precipitation patterns were revealed, and the importance of the timing uniformity of precipitation events to the functioning of production systems was highlighted, which is essential to enhancing understanding of the structures and functions of ecosystems subjected to altered precipitation patterns and predicting their changes.

Background: Patients with pathological stage IA lung adenocarcinoma (LUAD) are at risk of relapse. The value of the TNM staging system is limited in predicting recurrence. Our study aimed to develop a precise recurrence prediction model for stage IA LUAD. Materials and methods: Patients with pathological stage IA LUAD who received surgical treatment at Zhongshan Hospital Fudan University were retrospectively analyzed. Multivariate Cox proportional hazards regression models were used to create nomograms for recurrence-free survival (RFS). The predictive performance of the model was assessed using calibration plots and the concordance index (C-index). Results: The multivariate Cox regression analysis revealed that CTR (0.75 < CTR ≤ 1; HR = 9.882, 95% CI: 2.036–47.959, p = 0.004) and solid/micropapillary-predominance (SMPP; >5% and the most dominant) (HR = 4.743, 95% CI: 1.506–14.933, p = 0.008) were independent prognostic factors of RFS. These risk factors were used to construct a nomogram to predict postoperative recurrence in these patients. The C-index of the nomogram for predicting RFS was higher than that of the eighth T-stage system (0.873 for the nomogram and 0.643 for the eighth T stage). The nomogram also achieved good predictive performance for RFS with a well-fitted calibration curve. Conclusions: We developed and validated a nomogram based on CTR and SMP patterns for predicting postoperative recurrence in pathological stage IA LUAD. This model is simple to operate and has better predictive performance than the eighth T stage system, making it suitable for selecting further adjuvant treatment and follow-up.

IntroductionMénière’s disease (MD), a common disease in the inner ear, is characterized by an increase in endolymph in the cochlear duct and vestibular labyrinth. The pathophysiology of the condition appears to be the immune response. Studies have shown that basal levels of the IL-1β increased in some MD patients.MethodsHere, we used a murine model of endolymphatic hydrops (EH) to study the effect of anakinra on auditory and vestibular function. Mice were intraperitoneal injected with anakinra or saline before LPS by postauricular injection. Weight and disease severity were measured, histologic changes in auditory were assessed, and inflammation state was evaluated.ResultsWe found that anakinra therapy reduced LPS-induced EH, alleviated LPS-induced hearing loss and vestibular dysfunction, and inhibited the expression of the inflammatory cytokines and macrophage infiltration in the cochlea of mice. We further demonstrated that anakinra ameliorated the disorganization and degeneration of myelin sheath, and reduced the neuron damage in cochlea of EH mice.DiscussionConsequently, anakinra contributes to a promising therapeutic approach to MD, by restricting EH, alleviating auditory and vestibular function, inhibiting inflammation of the inner ear and protecting the cochlear nerve. Further investigations are needed to assess the potential therapeutic benefits of anakinra in patients with MD.

BackgroundMigraine plays an important role in some subgroups of children with recurrent vertigo. Moreover, the migraine component varies from definite to possibly absent as defined in this spectrum of three disorders—vestibular migraine of childhood (VMC), probable VMC (pVMC), and recurrent vertigo of childhood (RVC). However, studies on the sensory organization of balance control in these three disorders are rare.ObjectiveTo explore the balance control of children with RVC, VMC, and pVMC, when the three sensory systems are challenged.MethodA retrospective analysis was performed on 125 children with VMC (18 female and 15 male; aged 11.64 ± 2.74), pVMC (10 female and eight male; aged 11.78 ± 2.51), and RVC (32 female and 42 male; aged 11.10 ± 2.60). All children in each subtype were divided into groups of children aged ≤ 12 years old and 13–17 years old. Vestibular examination screening and assessment for postural control using the six conditions of the sensory organization test (SOT) were performed. The three primary outcome measures were: equilibrium score (ES), strategy score (SS), and sensory analysis score of the SOT.ResultsEquilibrium score under six different conditions and composite score increased with age (all P-values < 0.05). The somatosensory and visual scores also improved with growing (P-values < 0.05). However, vestibular scores did not increase significantly with age as the other senses did (P > 0.05). In the children ≤ 12 year-old group, children with VMC had a significantly higher visual preference score than those with pVMC and RVC (P < 0.05). There was an effect of age on the horizontal HIT. Ocular vestibular evoked myogenic potential (oVEMP), cervical vestibular evoked myogenic potential (cVEMP), and unilateral weakness (UW) values showed no significant difference among three diseases.ConclusionCompared with patients at the age of 13–17 years old and with RVC and pVMC (both ≤ 12 years old), children with VMC had a higher degree of reliance on visual signals to maintain their balance and a poorer central integration of peripheral information before reaching 12 years of age. In addition, vision may predominate by weakening vestibular function based on visuo-vestibular interactions. It must be noted that peripheral vestibular examinations could not distinguish the three disease subtypes.

In a complex market environment with fierce competition, maintaining their current market positions is an important issue for electric power companies. Sustainable development not only requires them to pay attention to their current operating efficiencies but also to actively participate in environmental and social responsibilities to maintain their competitive advantages. This paper proposes a model for evaluating the sustainable development capacities of power companies. Firstly, the preliminary evaluation indicator system is constructed with the seven dimensions of production safety, public relations and social welfare, shareholder rights protection, environmental sustainability, employee rights protection, scientific research innovation ability, and financial status. Then, specific financial indicators are selected by CART to avoid indicator redundancies and the final evaluation indicator system is constructed. Finally, the relative proximity calculated by the TOPSIS method is applied to evaluate the sustainable development capacities. An empirical study of 18 listed electric power companies is conducted to verify the evaluation model. The results show that the performances of these companies in production safety and environmental sustainability are generally satisfactory, but the overall performances in public relations and social welfare, employee rights protection, and scientific research innovation ability are relatively poor, so these dimensions should be strengthened. First published online 15 July 2022

Although conventional vaccine approaches have proven to be successful in preventing infectious diseases in past decades, for vaccine development against emerging/re-emerging viruses, one of the main challenges is rapid response in terms of design and manufacture. mRNA vaccines can be designed and produced within days, representing a powerful approach for developing vaccines. Furthermore, mRNA vaccines can be scaled up and may not have the risk of integration. mRNA vaccines are roughly divided into non-replicating mRNA vaccines and self-amplifying RNA (saRNA) vaccines. In this review, we provide an overview of saRNA vaccines, and discuss future directions and challenges in advancing this promising vaccine platform to combat emerging/re-emerging viruses.

Background: Although recent research suggests that alterations in gut microbiota and metabolites play a critical role in the pathophysiology of immunoglobulin A nephropathy (IgAN), the causal relationship between specific intestinal flora and metabolites and the risk of IgAN remains unclear. Method: This study employed Mendelian randomization (MR) to investigate the causal association between gut microbiota and IgAN. To explore potential associations between gut microbiota and various outcomes, four MR methods were applied: inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode. If the results of the four methods are inconclusive, we prefer the IVW as the primary outcome. Additionally, MR-Egger, MR-PRESSO-Global, and Cochrane’s Q tests were used to detect heterogeneity and pleiotropy. The stability of MR findings was assessed using the leave-one-out approach, and the strength of the causal relationship between exposure and outcome was tested using Bonferroni correction. Additional clinical samples were utilized to validate the results of Mendelian randomization, and the outcomes were visualized through an ROC curve, confusion matrix, and correlation analysis. Result: This study examined a total of 15 metabolites and 211 microorganisms. Among them, eight bacteria and one metabolite were found to be associated with the risk of IgAN (p < 0.05). The Bonferroni-corrected test reveals that only Class. Actinobacteria (OR: 1.20, 95% CI: 1.07–1.36, p = 0.0029) have a significant causal relationship with IgAN. According to Cochrane’s Q test, there is no substantial heterogeneity across different single-nucleotide polymorphisms (p > 0.05). Furthermore, MR-Egger and MR-PRESSO-Global tests (p > 0.05) showed no evidence of pleiotropy. No reverse causal association was found between the risk of IgAN and microbiota or metabolites (p > 0.05). Clinical specimens demonstrated the effectiveness and accuracy of Actinobacteria in distinguishing IgAN patients from those with other glomerular diseases (AUC = 0.9, 95% CI: 0.78–1.00). Additionally, our correlation analysis revealed a potential association between Actinobacteria abundance and increased albuminuria (r = 0.85) and poorer prognosis in IgAN patients (p = 0.01). Conclusion: Through MR analysis, we established a causal link between Actinobacteria and the incidence of IgAN. Moreover, clinical validation using fecal samples indicated that Actinobacteria might be associated with the onset and poorer prognosis of IgAN. This finding could provide valuable biomarkers for early, noninvasive detection of the disease and potential therapeutic targets in IgAN.

Abstract Hypopharyngeal squamous cell carcinoma (HPSCC) is one of the most common malignant tumors in otolaryngology head and neck surgery and is one of the worst prognostic malignant tumors. Endogenous circular RNA (circRNA) is more stable than mRNA, microRNA (miRNA), and long non-coding RNA (LncRNA) in exosomes, plasma, and urine, and participates in gene expression regulation to perform different functions. Therefore, circRNA is expected to become a biomarker and therapy target for many tumors. However, the expression and function of circRNA regulated by N6-methyladenosine (m6A) are still unclear in HNSCC. In this study, we demonstrated that a specific circRNA, circCUX1, was upregulated in HPSCC patients who are resistant to radiotherapy and predicts poor survival outcome. We further found that methyltransferase like 3 (METTL3) mediated the m6A methylation of circCUX1 and stabilizes its expression. Knockdown circCUX1 promotes the sensitivity of hypopharyngeal cancer cells to radiotherapy. In addition, circCUX1 binds to Caspase1 and inhibits its expression, resulting in a decrease in the release of inflammatory factors, thereby developing tolerance to radiotherapy. Our findings indicate that circCUX1 is a potential therapeutic target for radiotherapy tolerance in HPSCC patients.

Abstract Background Acupuncture is effective in symptom and quality of life improvement of chronic asthma, but the efficacy differences between different acupoints are uncertain. In terms of the theory of Meridian-viscera Association, the study aims to investigate the different effectiveness between acupoints in Lung meridian and the acupoints in Heart meridian, so as to provide the evidence to develop a better prescription of the acupuncture treatment of chronic persistent asthma. Methods This study is a multicentral randomized controlled trial. A total of 68 chronic persistent asthma patients will be randomly allocated into two groups: the Lung meridian group and the Heart meridian group. This trial will include a 2-week baseline period, a 4-week treatment period with 12 sessions’ acupuncture, and an 8-week follow-up period. The primary outcome is the Asthma Quality of Life Questionnaire (AQLQ). Secondary outcomes are the Asthma Control Test (ACT), Peak Expiratory Flow (PEF), and Forced Expiratory Volume in 1 s (FEV1). The AQLQ and ACT will be collected at baseline, week 4, week 8, and week 12 after randomization. PEF, FEV1, the Self-rating Anxiety Scale (SAS), and the Self-rating Depression Scale (SDS) will be assessed at baseline and week 4. Discussion The results will provide evidence for acupuncture prescription selection and the clinical efficacy improvement. The results of this trial will also be used to determine whether or not a full definitive trial will go ahead, which will further confirm the theory of Meridian-viscera Association. Trial registration Chinese Clinical Trial Registry ( http://www.chictr.org.cn/showproj.aspx?proj=43803 ) ChiCTR1900027284. Registered on 7 November 2019

Accurate monitoring of bare soil land (BSL) is an urgent need for environmental governance and optimal utilization of land resources. High-resolution imagery contains rich semantic information, which is beneficial for the recognition of objects on the ground. Simultaneously, it is susceptible to the impact of its background. We propose a semantic segmentation model, Deeplabv3+-M-CBAM, for extracting BSL. First, we replaced the Xception of Deeplabv3+ with MobileNetV2 as the backbone network to reduce the number of parameters. Second, to distinguish BSL from the background, we employed the convolutional block attention module (CBAM) via a combination of channel attention and spatial attention. For model training, we built a BSL dataset based on BJ-2 satellite images. The test result for the F1 of the model was 88.42%. Compared with Deeplabv3+, the classification accuracy improved by 8.52%, and the segmentation speed was 2.34 times faster. In addition, compared with the visual interpretation, the extraction speed improved by 11.5 times. In order to verify the transferable performance of the model, Jilin-1GXA images were used for the transfer test, and the extraction accuracies for F1, IoU, recall and precision were 86.07%, 87.88%, 87.00% and 95.80%, respectively. All of these experiments show that Deeplabv3+-M-CBAM achieved efficient and accurate extraction results and a well transferable performance for BSL. The methodology proposed in this study exhibits its application value for the refinement of environmental governance and the surveillance of land use.

Current COVID-19 vaccines need to take at least one month to complete inoculation and then become effective. Around 51% of the global population is still not fully vaccinated. Instantaneous protection is an unmet need among those who are not fully vaccinated. In addition, breakthrough infections caused by SARS-CoV-2 are widely reported. All these highlight the unmet needing for short-term instantaneous prophylaxis (STIP) in the communities where SARS-CoV-2 is circulating. Previously, we reported nanobodies isolated from an alpaca immunized with the spike protein, exhibiting ultrahigh potency against SARS-CoV-2 and its variants. Herein, we found that Nb22, among our previously reported nanobodies, exhibited ultrapotent neutralization against Delta variant with an IC50 value of 0.41 ng/ml (5.13 pM). Furthermore, the crystal structural analysis revealed that the binding of Nb22 to WH01 and Delta RBDs both effectively blocked the binding of RBD to hACE2. Additionally, intranasal Nb22 exhibited protection against SARS-CoV-2 Delta variant in the post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP). Of note, intranasal Nb22 also demonstrated high efficacy against SARS-CoV-2 Delta variant in STIP for seven days administered by single dose and exhibited long-lasting retention in the respiratory system for at least one month administered by four doses, providing a strategy of instantaneous short-term prophylaxis against SARS-CoV-2. Thus, ultrahigh potency, long-lasting retention in the respiratory system and stability at room-temperature make the intranasal or inhaled Nb22 to be a potential therapeutic or STIP agent against SARS-CoV-2.

Background Although it is known that obesity is inseparable from diabetes, many anthropometric indices are used for determining obesity. At the same time, research on the predictive indices of diabetes in Chinese minority populations is lacking. Therefore, this study determines the relationship between different anthropometric indices and diabetes, and identifies the best index and best cut-off values for predicting diabetes. Method In total, 11,035 Dong and Miao ethnic participants (age: 30–79 years) from the China Multi-Ethnic Cohort study were included. The logistic regression model was used to examine the relationship between the different anthropometric indices and diabetes risk. The receiver operating characteristic curve and the area under the curve (AUC) were used to identify the best predictor of diabetes. Results In multivariate adjusted logistic regression models, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), a body shape index (ABSI), body roundness index (BRI), and visceral adiposity index (VAI) were positively correlated with diabetes risk. Among Chinese Dong men and women and Miao men, WHR had the largest AUC (0.654/0.719/0.651). Among Miao women, VAI had the largest AUC(0.701). The best cut-off values of WHR for Dong men and women and Miao men were 0.94, 0.92, and 0.91, respectively. The best cut-off value of VAI for Miao women was 2.20. Conclusion Obesity indicators better predict diabetes in women than men. WHR may be the best predictor of diabetes risk in both sex of Dong ethnicity and Miao men, and VAI may be the best predictor of diabetes risk in Miao women.

The xenia effect refers to the phenomenon whereby the pollen genotype directly affects seed and fruit development during the period from fertilization to seed germination, which leads to different characteristics in phenotypic traits. The xenia effect can create differences in the endosperm and embryo formed after double fertilization and can also alter various fruit parameters, such as the fruit-ripening period; the fruit shape, size, and color; the flavor quality, such as sugars and acids; as well as the nutrient quality, such as anthocyanins. The xenia effect manifests in various ways, playing an important role in increasing the yield of fruit trees, improving fruit appearance and internal quality, as well as in directional breeding. Compared with other pomology research areas, our understanding of the xenia effect is still in its infancy. Currently, xenia is classified into two types: xenia and metaxenia. In the former, the direct effects of the pollen genotype are exhibited in the syngamous parts of the ovules; that is, the embryo and endosperm only. In the latter, the effects of the pollen genotype are demonstrated in structures other than the embryo and endosperm; that is, in tissues derived wholly from the mother plant material, in seed parts such as the nucellus and testa, as well as in the carpels and accessory tissues. However, the current classification has various shortcomings. In the present study, we propose a novel classification based on whether the appearance of xenia results from the tissue formed by double fertilization. Three xenia types are proposed: double-fertilization xenia, non–double-fertilization xenia, and combined xenia. The new classification has great theoretical and practical significance for future studies on the xenia effect and its mechanisms and also provides a more effective, broader application of xenia in improving the yield and quality of fruit trees.

The effects of increasing nitrogen (N) and phosphorus (P) deposition on the nutrient stoichiometry of soil and plant are gaining improving recognition. However, whether and how the responses of N cycle coupled with P of the soil–plant system to external N and P deposition in alpine grassland is still unclear. A short-term external N and P addition experiment was conducted in an alpine grazing grassland in the KunLun Mountain to explore the effects of short-term N and P addition on the nutrient stoichiometry in soil and plant. Different rates of N addition (ranging from 0.5 g N m−2 yr−1 to 24 g N m−2 yr−1) and P addition (ranging from 0.05 g N m−2 yr−1 to 3.2 g P m−2 yr−1) were supplied, and the soil available N, P, leaf N and P stoichiometry of Seriphidium rhodanthum which dominant in the alpine ecosystem were measured. Results showed that N addition increased soil inorganic N, leaf C, leaf N, and leaf N:P ratio but decreased soil available P and leaf C:P. Furthermore, P addition increased soil available P, leaf P, soil inorganic N, leaf N, and leaf C and reduced leaf C:N, C:P, and N:P ratios. Leaf N:P was positively related to N addition gradient. Leaf C:P and leaf N:P were significantly negatively related to P addition gradient. Although external N and P addition changed the value of leaf N:P, the ratio was always lower than 16 in all treatments. The influences of P addition on soil and plant mainly caused the increase in soil available P concentration. In addition, the N and P cycles in the soil–plant system were tightly coupled in P addition but decoupled in N addition condition. The nutrient stoichiometry of soil and leaf responded differently to continuous N and P addition gradients. These data suggested that the alpine grazing grassland was limited by P rather than N due to long-term N deposition and uniform fertilization. Moreover, increasing P addition alleviated P limitation. Therefore, the imbalanced N and P input could change the strategy of nutrient use of the grass and then change the rates of nutrient cycling in the alpine grassland ecosystem in the future.

Summary: The dramatically expanding coronavirus disease 2019 (COVID-19) needs multiple effective countermeasures. Neutralizing nanobodies (Nbs) are a potential therapeutic strategy for treating COVID-19. Here, we characterize several receptor binding domain (RBD)-specific Nbs isolated from an Nb library derived from an alpaca immunized with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (S); among them, three Nbs exhibit picomolar potency against SARS-CoV-2 live virus, pseudotyped viruses, and circulating SARS-CoV-2 variants. To improve their efficacy, various configurations of Nbs are engineered. Nb15-NbH-Nb15, a trimer constituted of three Nbs, is constructed to be bispecific for human serum albumin (HSA) and RBD of SARS-CoV-2. Nb15-NbH-Nb15 exhibits single-digit ng/ml neutralization potency against the wild-type and Delta variants of SARS-CoV-2 with a long half-life in vivo. In addition, we show that intranasal administration of Nb15-NbH-Nb15 provides effective protection for both prophylactic and therapeutic purposes against SARS-CoV-2 infection in transgenic hACE2 mice. Nb15-NbH-Nb15 is a potential candidate for both the prevention and treatment of SARS-CoV-2 through respiratory administration.

Objectives: This study was conducted in order to investigate the study design and main outcomes of acupuncture neuroimaging studies on low back pain (LBP).Methods: Neuroimaging studies of acupuncture on LBP were collected from three English databases such as PubMed and four Chinese databases such as China National Knowledge Infrastructure (CNKI) from inception to December 31, 2020. Study selection, data extraction, and assessment of risk of bias were performed independently by two investigators. The quality of studies was appraised with the Cochrane's risk of bias tools. Information on basic information, methodology, and brain imaging data were extracted.Results: The literature search returned 310 potentially eligible studies and 19 articles met inclusion criteria; 78.9% of studies chose manual acupuncture as the intervention, 89.5% of studies evaluated functional changes elicited by acupuncture, and 68.4% of studies used resting-state fMRI as imaging condition. The most frequently reported acupuncture-induced brain alterations of LBP patients were in the prefrontal cortex, insula, cerebellum, primary somatosensory cortex, and anterior cingulate cortex. There was a significant correlation between improved clinical outcomes and changes in the brain.Conclusions: The results suggested that improving abnormal structure and functional activities in the brain of the LBP patient is an important mechanism of acupuncture treatment for LBP. The brain regions involved in acupuncture analgesia for LBP were mainly located in the pain matrix, default mode network (DMN), salience network (SN), and descending pain modulatory system (DPMS). However, it was difficult to draw a generalized conclusion due to the heterogeneity of study designs. Further well-designed multimodal neuroimaging studies investigating the mechanism of acupuncture on LBP are warranted.

Waardenburg syndrome (WS) is an autosomal dominant inherited disorder that is characterized by sensorineural hearing loss and abnormal pigmentation. SOX10 is one of its main pathogenicity genes. The generation of patient-specific induced pluripotent stem cells (iPSCs) is an efficient means to investigate the mechanisms of inherited human disease. In our work, we set up an iPSC line derived from a WS patient with SOX10 mutation and differentiated into neural crest cells (NCCs), a key cell type involved in inner ear development. Compared with control-derived iPSCs, the SOX10 mutant iPSCs showed significantly decreased efficiency of development and differentiation potential at the stage of NCCs. After that, we carried out high-throughput RNA-seq and evaluated the transcriptional misregulation at every stage. Transcriptome analysis of differentiated NCCs showed widespread gene expression alterations, and the differentially expressed genes (DEGs) were enriched in gene ontology terms of neuron migration, skeletal system development, and multicellular organism development, indicating that SOX10 has a pivotal part in the differentiation of NCCs. It’s worth noting that, a significant enrichment among the nominal DEGs for genes implicated in inner ear development was found, as well as several genes connected to the inner ear morphogenesis. Based on the protein-protein interaction network, we chose four candidate genes that could be regulated by SOX10 in inner ear development, namely, BMP2, LGR5, GBX2, and GATA3. In conclusion, SOX10 deficiency in this WS subject had a significant impact on the gene expression patterns throughout NCC development in the iPSC model. The DEGs most significantly enriched in inner ear development and morphogenesis may assist in identifying the underlying basis for the inner ear malformation in subjects with WS.

Human norovirus (HuNoV) is the leading cause of epidemic acute gastroenteritis worldwide. Type I interferons (IFN)-α/β are highly potent cytokines that are initially identified for their essential roles in antiviral defense. It was reported that HuNoV infection did not induce IFN-β expression but was controlled in the presence of IFN-β in human intestinal enteroids and a gnotobiotic pig model, suggesting that HuNoV has likely developed evasion countermeasures. In this study, we found that a cDNA clone of GII.4 HuNoV, the predominantly circulating genotype worldwide, inhibits the production of IFN-β and identified the viral NTPase as a key component responsible for such inhibition. HuNoV NTPase not only inhibits the activity of IFN-β promoter but also the mRNA and protein production of IFN-β. Additional studies indicate that NTPase inhibits the phosphorylation and nuclear translocation of interferon-regulatory factor-3 (IRF-3), leading to the suppression of IFN-β promoter activation. Mechanistically, NTPase interacts with IkB kinase ε (IKKε), an important factor for IRF-3 phosphorylation, and such interaction blocks the association of IKKε with unanchored K48-linked polyubiquitin chains, resulting in the inhibition of IKKε phosphorylation. Further studies demonstrated that the 1-179 aa domain of NTPase which interacts with IKKε is critical for the suppression of IFN-β production. Our findings highlight the role of HuNoV NTPase in the inhibition of IFN-β production, providing insights into a novel mechanism underlying how HuNoV evades the host innate immunity.

Although the thermal conductivity of molten salt mixtures is of interest for many potential technological applications, precise values are often hard to obtain. In this study, the thermal diffusivity of FliNaK was studied in a molten state using the laser flash method and found to be very slightly dependent on temperature. The heat capacity of FliNaK was measured using the DSC method. There was a minor difference between our results and data from the literature. From calculations based on thermal diffusivity, density and heat capacity values, thermal conductivity was shown to decrease with temperature.

Accurate mapping of dams can provide useful information about geographical locations and boundaries and can help improve public dam datasets. However, when applied to disaster emergency management, it is often difficult to completely determine the distribution of dams due to the incompleteness of the available data. Thus, we propose an automatic and intelligent extraction method that combines location with post-segmentation for dam detection. First, we constructed a dataset named RSDams and proposed an object detection model, YOLOv5s-ViT-BiFPN (You Only Look Once version 5s-Vision Transformer-Bi-Directional Feature Pyramid Network), with a training method using deep transfer learning to generate graphical locations for dams. After retraining the model on the RSDams dataset, its precision for dam detection reached 88.2% and showed a 3.4% improvement over learning from scratch. Second, based on the graphical locations, we utilized an improved Morphological Building Index (MBI) algorithm for dam segmentation to derive dam masks. The average overall accuracy and Kappa coefficient of the model applied to 100 images reached 97.4% and 0.7, respectively. Finally, we applied the dam extraction method to two study areas, namely, Yangbi County of Yunnan Province and Changping District of Beijing in China, and the recall rates reached 69.2% and 81.5%, respectively. The results show that our method has high accuracy and good potential to serve as an automatic and intelligent method for the establishment of a public dam dataset on a regional or national scale.

Plasmid DNA (pDNA) represents a promising “genetic vaccine platform” capable of overcoming major histocompatibility complex barriers. We previously demonstrated that low-to-moderate doses of mucosae-associated epithelial chemokine (MEC or CCL28) as an immunomodulatory adjuvant can trigger effective and long-lasting systemic and mucosal HSV-2 gD-specific immune responses, whereas mice immunized with gD in combination with high-dose CCL28 showed toxicity and lost their immunoprotective effects after lethal HSV-2 challenge. The exact causes underlying high-dose, CCL28-induced lesions remain unknown. In an intramuscularly immunized mouse model, we investigated the immune-enhancement mechanisms of low-dose CCL28 as a molecular adjuvant combined with the relatively weak immunogen HSV-2 gB. Compared with the plasmid gB antigen group, we found that a low-dose of plasmid CCL28 (pCCL28) codelivered with pgB induced increased levels of gB-specific serum IgG and vaginal fluid IgA, serum neutralizing antibodies (NAb), Th1-polarized IgG2a, and cytokine IL-2 (>5-fold). Furthermore, low-dose pCCL28 codelivery with pgB enhanced CCL28/CCR10-axis responsive CCR10− plus CCR10+ B-cell (~1.2-fold) and DC pools (~4-fold) in the spleen, CCR10− plus CCR10+ T-cell pools (~2-fold) in mesenteric lymph nodes (MLNs), and the levels of IgA-ASCs in colorectal mucosal tissues, leading to an improved protective effect against a lethal dose of HSV-2 challenge. Findings in this study provide a basis for the development of CCL28-adjuvant vaccines against viral mucosal infections.

Geo-information technology has been playing an increasingly important role in environmental monitoring in recent decades. With the continuous improvement in the spatial resolution of remote sensing images, the diversification of sensors and the development of processing packages, applications of a variety of geo-information, in particular, multi-resolution remote sensing and geographical data, have become momentous in environmental research, including land cover change detection and modeling, land degradation assessment, geohazard mapping and disaster damage assessment, mining and restoration monitoring, etc. In addition, machine learning algorithms such as Random Forests (RF) and Convolutional Neural Networks (CNN) have improved and deepened the applications of geo-information technology in environmental monitoring and assessment. The purpose of this Special Issue is to provide a platform for communication of high-quality research in the world in the domain of comprehensive application of geo-information technology. It contains 10 high-level scientific papers on the following topics such as desertification monitoring, governance of mining areas, identification of marine dynamic targets, extraction of buildings, and so on.

Waardenburg Syndrome (WS) is a common autosomal dominant syndrome associated with hearing loss. Its clinical manifestations include hearing impairment and pigmentation anomalies. In this study, we generated an induced pluripotent stem cell (iPSC) line from the Epstein–Barr virus-immortalized B lymphocytes of a 6-year-old boy affected with WS type I, caused by a heterozygous splice site mutation in the PAIRED BOX GENE 3 (PAX3) (NM_181457.3: c.452-2A > G). The patient-specific iPSC line (CSUXHi004-A) carrying the same PAX3 mutation showed a normal karyotype, expressed pluripotent markers, and presented differentiation capacity in vitro. This method may be a useful tool for the in vitro modeling of WS.

The level of acidity in rainfall can alter soil nutrient cycling (e.g., carbon [C] cycling), while the effect of changing acid rain frequency on soil C cycling and involved microbial communities remains largely understudied. Here, we manipulated a laboratory intact soil core experiment to test the effect of acid rain frequency (0, 30% and 100%) on soil CO2 emission, microbial communities, and microbial metabolism of various carbon sources in the agricultural and forest soils in southern China. We found idiosyncratic responses of soil microbial communities and carbon utilization to acid rain frequency in two different soil ecosystems. The high acid rain frequency (100%) substantially reduced soil microbial biomass, particularly that of gram-negative bacteria in the forest soil, while this effect was not observed in the agricultural soil. Moreover, acid rain frequencies (30% and 100%) significantly reduced the microbial utilization of amines/amides in the agricultural soil, while they did not alter the carbon sources utilization in the forest soil. However, surprisingly, both the acid rain treatments did not affect the soil CO2 emission in the agricultural and forest soils, suggesting a complex relationship between soil microbial biomass or abundance and CO2 emission. Our results suggest that the agricultural and forest soils have idiosyncratic responses to changing acid rain frequency, probably because of differences in their biological and physicochemical properties.

An effective HSV-2 vaccine should induce antigen (Ag)-specific immune responses against viral mucosal infection. This study reveals that chemokine CCL19 or CCL28 enhanced HSV-2 glycoprotein D ectodomain (gD-306aa)-induced immune responses against vaginal virus challenge.