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Abstract Background Sarcopenia is highly prevalent in elderly individuals and has a significant adverse effect on their physical health and quality of life, but the mechanisms remain unclear. Studies have indicated that transcription factors (TFs) and the immune microenvironment play a vital role in skeletal muscle atrophy. Methods RNA-seq data of 40 muscle samples were downloaded from the GEO database. Then, differentially expressed genes (DEGs), TFs(DETFs), pathways(DEPs), and the expression of immune gene sets were identified with limma, edgeR, GO, KEGG, ORA, GSVA, and ssGSEA. Furthermore, the results above were integrated into coexpression analysis by Pearson correlation analysis (PCA). Significant coexpression patterns were used to construct the immune-related transcriptional regulatory network by Cytoscape and potential medicine targeting the network was screened by Connectivity Map. Finally, the regulatory mechanisms and RNA expression of DEGs and DETFs were identified by multiple online databases and RT‒qPCR. Results We screened 808 DEGs (log2 fold change (FC) > 1 or 0.7 or 1 or 0.4 or

Magnesium (Mg) is the central atom of the chlorophyll porphyrin ring and plays an important role in the degradation of chlorophyll. In this study, the Mg contents in cigar tobacco leaves (Folium cigarum) under different fertilization (no (CK), NPK (NPK), and NPK+MgO (NKP+Mg)) were investigated by a field experiment, and the effects of Mg in cigar tobacco leaves on the chlorophyll degradation and leaf chroma during airing period were analyzed. The results showed that the application of Mg fertilization significantly increased Mg contents in cigar tobacco leaves. The chromaticity values (luminance value L*, red-green value a*, yellow-blue value b*, and total color difference value ΔE) of cigar tobacco leaves in NPK+Mg treatment were lower than other treatments during the airing. The contents of chlorophyll a (Chl a), chlorophyll b (Chl b), and total chlorophyll (TC) were decreased rapidly in the first eight airing days, and the decreasing trend of total chlorophyll/carotenoid (TC/Car) was more smoothly in NPK+Mg treatment than other treatments. The chromaticity values (L*, a*, b*, ΔE) were extremely significantly negatively correlated with pigment contents (Chl a, Chl b, TC, Car), which indicated that the leaf color was determined by the pigment contents. The activities of pheophytin pheophorbide hydrolase (PPH) in NPK+Mg treatment were the highest, while the activities of chlorophyllase (CLH) had no significant difference among the three treatments. The PPH activities were extremely significantly positively correlated with pigment contents (Chl a, Chl b, TC, Car), and significantly negatively correlated with ΔE values, but the CLH activities were not correlated with pigment contents and ΔE. Therefore, the application of Mg fertilizer was beneficial to chlorophyll degradation by increasing the PPH activities of cigar tobacco leaves, and then it regulated the formation of leaf color.

Summary: Background: Multiple myeloma (MM) is an incurable hematological malignancy of the plasma cells. The maintenance of protein homeostasis is critical for MM cell survival. Elevated levels of paraproteins in MM cells are cleared by proteasomes or lysosomes, which are independent but inter-connected with each other. Proteasome inhibitors (PIs) work as a backbone agent and successfully improved the outcome of patients; however, the increasing activity of autophagy suppresses the sensitivity to PIs treatment. Methods: The transcription levels of CRIP1 were explored in plasma cells obtained from healthy donors, patients with newly diagnosed multiple myeloma (NDMM), and relapsed/refractory multiple myeloma (RRMM) using Gene expression omnibus datasets. Doxycycline-inducible CRIP1-shRNA and CRIP1 overexpressed MM cell lines were constructed to explore the role of CRIP1 in MM pathogenesis. Proliferation, invasion, migration, proteasome activity and autophagy were examined in MM cells with different CRIP1 levels. Co-immunoprecipitation (Co-IP) with Tandem affinity purification/Mass spectrum (TAP/MS) was performed to identify the binding proteins of CRIP1. The mouse xenograft model was used to determine the role of CRIP1 in the proliferation and drug-resistance of MM cells. Findings: High CRIP1 expression was associated with unfavorable clinical outcomes in patients with MM and served as a biomarker for RRMM with shorter overall survival. In vitro and in vivo studies showed that CRIP1 plays a critical role in protein homeostasis via the dual regulation of the activities of proteasome and autophagy in MM cells. A combined analysis of RNA-seq, Co-IP and TAP/MS demonstrated that CRIP1 promotes proteasome inhibitors resistance in MM cells by simultaneously binding to de-ubiquitinase USP7 and proteasome coactivator PA200. CRIP1 promoted proteasome activity and autophagosome maturation by facilitating the dequbiquitination and stabilization of PA200. Interpretation: Our findings clarified the pivotal roles of the CRIP1/USP7/PA200 complex in ubiquitin-dependent proteasome degradation and autophagy maturation involved in the pathogenesis of MM. Funding: A full list of funding sources can be found in the acknowledgements section.

Summary: Background: Genomic variants outside of the canonical splicing site (±2) may generate abnormal mRNA splicing, which are defined as non-canonical splicing variants (NCSVs). However, the clinical interpretation of NCSVs in neurodevelopmental disorders (NDDs) is largely unknown. Methods: We investigated the contribution of NCSVs to NDDs from 345,787 de novo variants (DNVs) in 47,574 patients with NDDs. We performed functional enrichment and protein–protein interaction analysis to assess the association between genes carrying prioritised NCSVs and NDDs. Minigene was used to validate the impact of NCSVs on mRNA splicing. Findings: We observed significantly more NCSVs (p = 0.02, odds ratio [OR] = 2.05) among patients with NDD than in controls. Both canonical splicing variants (CSVs) and NCSVs contributed to an equal proportion of patients with NDD (0.76% vs. 0.82%). The candidate genes carrying NCSVs were associated with glutamatergic synapse and chromatin remodelling. Minigene successfully validated 59 of 79 (74.68%) NCSVs that led to abnormal splicing in 40 candidate genes, and 9 of the genes (ARID1B, KAT6B, TCF4, SMARCA2, SHANK3, PDHA1, WDR45, SCN2A, SYNGAP1) harboured recurrent NCSVs with the same variant present in more than two unrelated patients with NDD. Moreover, 36 of 59 (61.02%) NCSVs are novel clinically relevant variants, including 34 unreported and 2 clinically conflicting interpretations or of uncertain significance NCSVs in the ClinVar database. Interpretation: This study highlights the common pathology and clinical importance of NCSVs in unsolved patients with NDD. Funding: The present study was funded by grants from the National Natural Science Foundation of China, China Postdoctoral Science Foundation, the Hunan Youth Science and Technology Innovation Talent Project, the Provincial Natural Science Foundation of Hunan, The Scientific Research Program of FuRong laboratory, and the Natural Science Project of the University of Anhui Province

The Internet of Things (IoT) refers to the use of various communication technologies to achieve the interconnection of everything in cyberspace, and to achieve smart home and intelligent transportation, thus generating unprecedented amounts of data. In the financial sharing center, all businesses can extract effective data from these massive databases for analysis, and use data analysis tools to collect business, financial, human, process, knowledge and social data. At present, various types of IT (Internet Technology) systems have been widely used in financial sharing centers. However, a large number of sensitive data have also been generated. In order to protect these sensitive data, there is a high requirement for the personal information of IT system operation and financial sharing center personnel. In order to protect user data privacy, the optimal and most effective use of IT systems is an important issue that must be considered in privacy management. At present, there are many algorithms to protect data and privacy, but the effect is not ideal. Considering the balance between privacy issues, this paper proposed a K-means clustering algorithm based on IoT public cloud privacy protection technology to analyze the performance management of financial sharing center. The research results showed that before the improvement, the average number of employees who were dissatisfied with the post training ability and information platform construction ability of the financial sharing center was 57.9 and 57.8% respectively, more than half of them. After the improvement of IoT based public cloud privacy protection, the average number of employees dissatisfied with the post training ability and information platform construction ability of the financial sharing center was 5 and 3.9%, far less than the data prior to the improvement. It showed that IoT public cloud privacy protection was conducive to the performance management of the financial sharing center, and the relationship between the two was positive.

Abstract Long non-coding RNAs (lncRNAs) have been functionally characterised in various diseases. LncRNA PAX-interacting protein 1-antisense RNA 1 (PAXIP1-AS1) has reportedly been associated with cancer development. However, its role in gastric cancer (GC) remains poorly understood. Here, we showed that PAXIP1-AS1 was transcriptionally repressed by homeobox D9 (HOXD9) and was significantly downregulated in GC tissues and cells. Decreased expression of PAXIP1-AS1 was positively correlated with tumour progression, while PAXIP1-AS1 overexpression inhibited cell growth and metastasis both in vitro and in vivo. PAXIP1-AS1 overexpression significantly attenuated HOXD9-enhanced epithelial-to-mesenchymal transition (EMT), invasion and metastasis in GC cells. Poly(A)-binding protein cytoplasmic 1 (PABPC1), an RNA-binding protein, was found to enhance the stability of PAK1 mRNA, leading to EMT progress and GC metastasis. PAXIP1-AS1 was found to directly bind to and destabilise PABPC1, thereby regulating EMT and metastasis of GC cells. In summary, PAXIP1-AS1 suppressed metastasis, and the HOXD9/PAXIP1-AS1/PABPC1/PAK1 signalling axis may be involved in the progression of GC.

In this work, cis-1,4-polybutadiene rubber/polystyrene-butadiene rubber (BR/SBR) blend was filled with inorganic lightweight filler hollow glass microspheres (HGMs) to develop a rubber-based lightweight composite. Cu-plating was carried out on the surface of HGMs by polydopamine (PDA) and Ag nanoparticles to improve the compatibility among HGMs and rubber matrix. Filter paper experiment, X-ray energy dispersive spectroscopy (EDS) and X-ray photoelectron spectrometer (XPS) were used to analyze the bonding mechanism between Cu-plated HGMs and rubber. The results confirmed that the redox reaction between the reactive sulfur in the rubber matrix and Cu on the surface of Cu-plated HGM can be successfully carried out at 170°C. And the compatibility between HGM and rubber matrix was obviously improved after Cu plating. The physical-mechanical properties and abrasion resistance of the composites were improved significantly. This research was of great significance to marine flexible floating body materials.

Uveal melanoma (UM) is the most common primary intraocular cancer in the adult population. Recent studies suggested that the NLRP3 inflammasome could be a therapeutic target for cutaneous melanoma (CM), but the role of NLRP3 in UM remains unknown. Here, we analyzed the NLRP3‐IL‐1β axis in 5 UM and 4 CM cell lines. Expression of NLRP3 mRNA in UM and CM was low, and expression in UM was lower than in CM (P

Radiotherapy and chemotherapy are effective treatments for patients with locally advanced rectal cancer (LARC) and can significantly improve the likelihood of R0 resection. Radiotherapy can be used as a local treatment to reduce the size of the tumor, improve the success rate of surgery and reduce the residual cancer cells after surgery. Early chemotherapy can also downgrade the tumor and eliminate micrometastases throughout the body, reducing the risk of recurrence and metastasis. The advent of neoadjuvant concurrent radiotherapy (nCRT) and total neoadjuvant treatment (TNT) has brought substantial clinical benefits to patients with LARC. Even so, given increasing demand for organ preservation and quality of life and the disease becoming increasingly younger in its incidence profile, there is a need to further explore new neoadjuvant treatment options to further improve tumor remission rates and provide other opportunities for patients to choose watch-and-wait (W&W) strategies that avoid surgery. Targeted drugs and immunologic agents (ICIs) have shown good efficacy in patients with advanced rectal cancer but have not been commonly used in neoadjuvant therapy for patients with LARC. In this paper, we review several aspects of neoadjuvant therapy, including radiation therapy and chemotherapy drugs, immune drugs and targeted drugs used in combination with neoadjuvant therapy, with the aim of providing direction and thoughtful perspectives for LARC clinical treatment and research trials.

Abstract To investigate the role of tracheal wall injury in the development of benign airway stenosis in rabbits. Prospective study. We injured the tracheal walls of 28 New Zealand white rabbits using four different methods. Experimental group: Group A (n = 7, mild injury of tracheal mucosa by ordinary brush under bronchoscopy); Group B (n = 7, severe injury of tracheal mucosa by nylon brush under tracheotomy); Group C (n = 7, tracheal cartilage was injured by vascular clamp after tracheotomy); Group D (n = 7, the tracheal cartilage was injured with vascular forceps and the tracheal mucosa was injured with a nylon brush after tracheotomy). Bronchoscopy was performed on each experimental rabbit at 1, 2, 3 and 4 weeks after operation. High-resolution computed tomography (HRCT) and endobronchial optical coherence tomography (EB-OCT) were performed at 4 weeks, and the rabbits were sacrificed after the examination. Their gross and histological findings were comparatively determined whether the experimental rabbit stenosis was established. No airway stenosis was observed in group A. In group B, 28.57% of experimental rabbits developed tracheal stenosis (granulation tissue proliferation was observed in rabbits No. 2 and No. 6 at 1, 2 and 3 weeks after operation, and the tracheal scar contracture was observed in No.6 rabbit at 4 weeks after operation). Fourteen rabbits in group C and group D had tracheal stenosis caused by granulation tissue proliferation at 1, 2 and 3 weeks after operation. At the fourth week after operation, 71.43% of experimental rabbits had tracheal stenosis due to granulation tissue hyperplasia, 7.14% of experimental rabbits had tracheal stenosis due to scar contracture and granulation hyperplasia, and 21.43% of experimental rabbits had tracheal stenosis due to scar contracture. EB-OCT scan showed that the cartilage layer with low signal reflection band was discontinuous. The injury of cartilage is the key factor of benign airway stenosis. Acute injury of airway mucosa alone is unlikely to cause airway stenosis, but combined with cartilage injury may aggravate airway stenosis. EB-OCT can clearly identify the airway layers of rabbits, which is helpful to evaluate the damage of tracheal cartilage and mucosa. The diagnostic potential of this technique makes EB-OCT a promising approach for the study and monitoring of airway diseases.

The microbial metabolism in vinegar is closely related to the flavor quality of vinegar, which has attracted the attention of researchers due to the diversity of microbes and flavor substances and their complex correlation. Exploring its research hot spots, evolution process and development trend is of great significance to guide the further research in this field. This paper used Cite Space to analyze the research hot spots, emerging trends and knowledge flow in the field of microbial diversity and flavor substance changes at home and abroad in the past 20 years, reflecting the research progress in this field in the past two decades. The results showed that the research heat of vinegar microbial diversity and flavor changes at home and abroad remained unchanged. Solid state fermentation, Chinese grain vinegar, acetic acid bacteria, metabolic characteristics, biological heat, and key environmental drivers were the main research directions in this field. The changes of knowledge flow in this research area were mainly from science, molecular, biology, immunology journals to environmental, toxicology, nutrition, molecular biology, genetics journals. Dynamics, solid state fermentation and volatile compounds would become new research hot spots.

Difficult and labour-intensive transportation up and down the steps is a challenge in small spaces. This work focused on the smooth performance requirements about each joint structure of robot foot. We have made research on the hand and foot structure of the transport part, which simplifies its posture calculation in the designed bipedal transport robot model. Methods for determination of each joint angle of the hand and foot are presented, including the use of standard D-H method to establish a mathematical model and perform forward and inverse kinematic analysis to derive the angles of each joint, where the matrix was coded by Python software to ensure the accuracy of the calculated results. The joints angles are assigned by the Step function, and the motion of the bipedal robot in the case of single access is simulated by the inverse kinematic derivation formula. Simulation results show that the structure of the robot's joints meets the requirement of maintaining the stability of the robot when going up and down the stairs.

This design proposes a self-grounding semi-circular gap dual-band flexible antenna in the context of the rapid development of wireless body area networks. The antenna combines the slit structure with the characteristics of traditional rectangular monopole antenna to realize dual-band. In addition, the antenna’s grounding structure adopts the self-grounding structure, which is less used nowadays, to extend the bandwidth. The antenna is designed on a dielectric board of polyimide material with a relative dielectric constant of 3.5. The overall dimensions of the antenna are 44 mm $\times 40$ mm $\times 0.2$ mm with two different sized gaps in a rectangular patch, similar to the geometry of an umbrella handle. Measured data shows that the structure has higher gain and efficiency in the bent state than in the flat state, making it ideal for wearable smart terminals. It can be combined with a smart armband for sports and medical applications or for a single soldier wearable wristband smartwatch. The article explores the effect of different slot sizes and different bending angles on the performance of the antenna, as well as the specific absorption rate values of the antenna for the human body. Finally, two frequency bands with good omnidirectional radiation characteristics are obtained: 2.38–2.81 GHz and 4.28–5.10 GHz. The antenna covers ISM, 4G, 5G, Bluetooth, WLAN, and other common communication frequency bands. The results of the study show that the design method is highly reliable.

Abstract Background Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disease caused by mutations in the Serine-Threonine Kinase 11 (STK11) gene. This study aimed to diagnose a Chinese pedigree with PJS and to expand the spectrum of STK11 variants. Methods We performed an inductive analysis of clinical features, gastrointestinal endoscopy, radiologic imaging, and pathological findings in a Chinese family with PJS. Whole-exome sequencing (WES), Sanger sequencing, and STK11 protein 3D structure prediction were performed for establishing a molecular diagnosis. Results The proband, her mother, and grandfather presented with pigmentation spots on lips, oral mucosa, and fingers. Her mother and grandfather also had pigmentation spots on face and feet, while her brother had pigmentation spots only on the lower lip. On endoscopy, polyps were discovered in the proband, her mother, and grandfather. A novel heterozygous mutation (c.521A > C) in exon 4 of STK11 was identified in all four patients, leading to a change from histidine to proline in amino acid 174. The variable site p.H174 was highly conserved in different species on multiple sequence alignment analysis. Conclusions We diagnosed a Chinese pedigree with PJS based on clinical features, gastrointestinal endoscopy, and genetic testing results. Our results expanded the spectrum of STK11 variants, which will be helpful for genetic counseling.

Abstract Ultraviolet light A (UVA) is the only UV light that reaches the retina and can cause indirect damage to DNA via absorption of photons by non-DNA chromophores. Previous studies demonstrate that UVA generates reactive oxygen species (ROS) and leads to programmed cell death. Programmed cell death (PCD) has been implicated in numerous ophthalmologic diseases. Here, we investigated receptor interacting protein 1 and 3 (RIPK1 and RIPK3) kinases, key signaling molecules of PCD, in UVA-induced photoreceptor injury using in vitro and ex vivo models. UVA irradiation activated RIPK3 but not RIPK1 and mediated necroptosis through MLKL that lie downstream of RIPK3 and induced apoptosis through increased oxidative stress. Moreover, RIPK3 but not RIPK1 inhibition suppresses UVA-induced cell death along with the downregulation of MLKL and attenuates the levels of oxidative stress and DNA fragmentation. In conclusion, these results identify RIPK3, not RIPK1, as a critical regulator of UVA-induced necroptosis cell death in photoreceptors and highlight RIPK3 potential as a neuroprotective target.

Abstract The measurement of the stiffness of a precision reducer is essential to estimating the reducer. Since the angular sensor’s measurement results include the angle measurement error caused by the instrument’s torsional deformation, it cannot be used as the actual torsional deformation of the reducer. This paper analyzes the instrument’s torsional deformation characteristics to reduce the angle measurement error. Based on the analysis, a new method of calibrating the angle measurement error based on the improved B-spline curve fitting-gradient descent and particle swarm optimization -radial basis function neural network (IBSCF-GDPSO-RBF) method is proposed. The method can eliminate the angle measurement error caused by the instrument’s torsional deformation. The steps of the IBSCF-GDPSO-RBF method are presented, and the angular measurement error compensation is executed under load conditions. The experiment shows that the instrument deformation caused angle measurement error after compensation is within ± two angular seconds. This paper’s innovation proposes the error calibration method based on the IBSCF-GDPSO-RBF method. It provides a reference for measuring and evaluating the actual torsional rigidity of the Rotary Vector (RV) reducer under any load.

Abstract Background Waldenström macroglobulinemia (WM) is a rare and incurable indolent B-cell malignancy. The molecular pathogenesis and the role of immunosuppressive microenvironment in WM development are still incompletely understood. Methods The multicellular ecosystem in bone marrow (BM) of WM were delineated by single-cell RNA-sequencing (scRNA-seq) and investigated the underlying molecular characteristics. Results Our data uncovered the heterogeneity of malignant cells in WM, and investigated the kinetic co-evolution of WM and immune cells, which played pivotal roles in disease development and progression. Two novel subpopulations of malignant cells, CD19+CD3+ and CD138+CD3+, co-expressing T-cell marker genes were identified at single-cell resolution. Pseudotime-ordered analysis elucidated that CD19+CD3+ malignant cells presented at an early stage of WM-B cell differentiation. Colony formation assay further identified that CD19+CD3+ malignant cells acted as potential WM precursors. Based on the findings of T cell marker aberrant expressed on WM tumor cells, we speculate the long-time activation of tumor antigen-induced immunosuppressive microenvironment that is involved in the pathogenesis of WM. Therefore, our study further investigated the possible molecular mechanism of immune cell dysfunction. A precursor exhausted CD8-T cells and functional deletion of NK cells were identified in WM, and CD47 would be a potential therapeutic target to reverse the dysfunction of immune cells. Conclusions Our study facilitates further understanding of the biological heterogeneity of tumor cells and immunosuppressive microenvironment in WM. These data may have implications for the development of novel immunotherapies, such as targeting pre-exhausted CD8-T cells in WM.

Thermoplastic elastomer foam is often used as a midsole, which is an important factor affecting sports efficiency. In this research, ethylene vinyl acetate copolymer/polyolefin elastomer/styrene ethylene butylene styrene (EVA/POE/SEBS) microcellular foam was prepared with supercritical nitrogen gas (SC-N2). The influence of the formulation ratio on the matrix network structure was studied by vulcanization curve and rheometric expansion system rheometer. Then the foaming behavior and static/dynamic mechanical properties were studied, and midsole was prepared. The results showed that the increase of the relative content of SEBS reduced the viscosity of the matrix, but the loss factor increased, which further reduced the resistance to cell growth and increased the expansion ratio (density decreased from 0.19 to 0.13 g/cm3). In addition, the increase of SEBS resulted in an increase in the static compressive strength and resilience (61%) of the foam. However, after 100 000 dynamic compression cycles, the increase of SEBS resulted in a decrease in the energy absorption capacity of the foam and an increase in the dynamic compression set (from 6.8 to 9.4%). This is significantly different from the traditional physical and mechanical performance test results, which are rarely reported and have significance for practical applications.

The impact of land-use and cover-change (LUCC) on ecosystem carbon stock in China is poorly known due to large biases in existing databases. Here the authors develop a new LUCC database with corrected false signals and reveal that forest expansion is the dominant driver of China’s recent carbon sink.

Sarcopenia is an age-related skeletal muscle disorder that causes falls, disability and death in the elderly, but its exact mechanism remains unknown. In this study, we merged three GEO datasets into the expression profiles of 118 samples and screened 22 differentially expressed genes (DEGs) as candidate genes. Pathway analysis demonstrated that the functional enrichment of DEGs is mainly in the cellular response to insulin stimulus, PPAR signaling pathway and other metabolism-related pathways. Then, we identified six key genes by machine learning, which were confirmed to be closely associated with sarcopenia by bioinformatics analysis. It was experimentally verified that SCD1 exhibits the most substantial alterations in the progression of sarcopenia with disturbed lipid metabolism and myosteatosis. In addition, the immune microenvironment of sarcopenia was found to be affected by these key genes, with Th17 cells down-regulated and NK cells up-regulated. Sarcopenic patients consequently presented a more significant systemic inflammatory state with higher CAR (p = 0.028) and PAR (p = 0.018). For the first time, we identified key genes in sarcopenia with high-throughput data and demonstrated that key genes can regulate the progression of sarcopenia by affecting the immune microenvironment. Among them, SCD1 may influence lipid metabolism and myosteatosis process. Screening of key genes and analyzing of immune microenvironment provide a more accurate target for treating sarcopenia.

The emergence of SARS-CoV-2 has brought olfactory dysfunction to the forefront of public awareness, because up to half of infected individuals could develop olfactory dysfunction. Loss of smell—which can be partial or total—in itself is debilitating, but the distortion of sense of smell (parosmia) that can occur as a consequence of a viral upper respiratory tract infection (either alongside a reduction in sense of smell or as a solo symptom) can be very distressing for patients. Incidence of olfactory loss after SARS-CoV-2 infection has been estimated by meta-analysis to be around 50%, with more than one in three who will subsequently report parosmia. While early loss of sense of smell is thought to be due to infection of the supporting cells of the olfactory epithelium, the underlying mechanisms of persistant loss and parosmia remain less clear. Depletion of olfactory sensory neurones, chronic inflammatory infiltrates, and downregulation of receptor expression are thought to contribute. There are few effective therapeutic options, so support and olfactory training are essential. Further research is required before strong recommendations can be made to support treatment with steroids, supplements, or interventions applied topically or injected into the olfactory epithelium in terms of improving recovery of quantitative olfactory function. It is not yet known whether these treatments will also achieve comparable improvements in parosmia. This article aims to contextualise parosmia in the setting of post-viral olfactory dysfunction, explore some of the putative molecular mechanisms, and review some of the treatment options available.

CH4 is one of the most important greenhouse gases responsible for climate change. The effect of algal decomposition on CH4 emission fluxes in aquaculture environments is unknown. This study determined the relative abundance of methanogens in aquaculture in northern China. We determined various parameters in the water and sediment after the decomposition of Chaetomorpha valida. The results showed that the relative abundance of methanogens increased significantly during the decomposition of C. valida. The average CH4 emission flux was 50.64 mg m-2 h-1 when the density of C. valida was 25 mg cm-3, which was 11 times higher than that at a density of 0 mg cm-3. The concentrations of dissolved oxygen (DO), nitrite, nitrate and sulfate in the aquaculture pond significantly decreased during the decomposition of C. valida. The formation of a strong anaerobic reduction environment promoted the formation and release of CH4. Our results confirmed that the decomposition of C. valida enhanced the CH4 emission flux. The average CH4 emission fluxes ranged from 4.62 to 50.64 mg m-2 h-1. It is particularly important to remove decomposed algae in a timely manner and control greenhouse gas emissions from aquaculture ponds to mitigate climate change.

As one of the most densely populated and economically developed regions in China, Yangtze River Delta (YRD) has confronted with substantial land cover change (LCC) over the past several decades. This study investigates the impact of climate change and LCC on carbon dynamics in the YRD region for 1990–2019, taking advantage of a high-resolution vegetation model and two well-established LCC data in China. Simulated gross primary productivity increases from 0.52 ± 0.02 Pg[C] yr ^−1 in the 1990s to 0.57 ± 0.01 Pg[C] yr ^−1 in the 2010s with the major contribution by CO _2 fertilization effect. The regional carbon sink, measured as net biospheric productivity (NBP), peaks at 0.03 Pg[C] yr ^−1 in the 2000s but remains stable or slightly decreases in the 2010s depending on the LCC datasets. Forests act as the main contributors to the enhancement of the regional carbon sink, with negative contributions from the loss of shrubland and grassland. The stable NBP during 2000–2019 suggests a potential slowdown in the efficacy of carbon sink as forests mature. While forest expansion significantly promotes NBP, the carbon released during the replacement of other vegetation types suggests that afforestation efforts need to be complemented with associated supportive measures to prevent newly forested areas from becoming net carbon sources.

Numerous evapotranspiration (ET) products have been produced using various approaches and diverse forcing data even as the magnitude and trends of ET show divergence. We simulated ET using updated land use and cover change (LUCC) data in China from 1900 to 2020. We found that China’s ET increased slightly from 1900 to 1980, but it increased rapidly after 1980 due to LUCC characterized by forest expansion (2.05 mm yr ^−1 , P < 0.01). We also found that the ET trends derived from our simulation were significantly higher than other ET products (−0.70–1.47 mm yr ^−1 , P < 0.01), implying that existing, long-term ET products might have underestimated ET trends in China during the post-1980 period because of underrepresented LUCC. These underestimated ET trends could introduce biases in the regional water budget and water resources management. We advocate for future studies to take into account the impacts of LUCC in global ET simulations.

In order to realize the economic dispatch and safety stability of offshore wind farms, and to address the problems of strong randomness and strong time correlation in offshore wind power forecasting, this paper proposes a combined model of principal component analysis (PCA), sparrow algorithm (SSA), variational modal decomposition (VMD), and bidirectional long- and short-term memory neural network (BiLSTM). Firstly, the multivariate time series data were screened using the principal component analysis algorithm (PCA) to reduce the data dimensionality. Secondly, the variable modal decomposition (VMD) optimized by the SSA algorithm was applied to adaptively decompose the wind power time series data into a collection of different frequency components to eliminate the noise signals in the original data; on this basis, the hyperparameters of the BiLSTM model were optimized by integrating SSA algorithm, and the final power prediction value was obtained. Ultimately, the verification was conducted through simulation experiments; the results show that the model proposed in this paper effectively improves the prediction accuracy and verifies the effectiveness of the prediction model.

Heating, ventilation and air conditioning (HVAC) systems account for approximately 50% of the total energy consumption in buildings. Advanced control and optimal operation, seen as key technologies in reducing the energy consumption of HVAC systems, indispensably rely on an accurate prediction of the building’s heating/cooling load. Therefore, the goal of this research is to develop a model capable of making such accurate predictions. To streamline the process, this study employs sensitivity and correlation analysis for feature selection, thereby eliminating redundant parameters, and addressing distortion problems caused by multicollinearity among input parameters. Four model identification methods including multivariate polynomial regression (MPR), support vector regression (SVR), multilayer perceptron (MLP), and extreme gradient boosting (XGBoost) are implemented in parallel to extract value from diverse building datasets. These models are trained and selected autonomously based on statistical performance criteria. The prediction models were deployed in a nearly zero-energy office building, and the impacts of feature selection, training set size, and real-world uncertainty factors were analyzed and compared. The results showed that feature selection considerably improved prediction accuracy while reducing model dimensionality. The research also recognized that prediction accuracy during model deployment can be influenced significantly by factors like personnel mobility during holidays and weather forecast uncertainties. Additionally, for nearly zero-energy buildings, the thermal inertia of the building itself can considerably impact prediction accuracy in certain scenarios.

Through a large number of light and thin section identification under the microscope, a large number of mineral particle size and content measurement statistics, the main useful mineral purification, X-ray analysis, chemical multi-element analysis and other comprehensive research means, the detailed mineralogy, mineralogy and deposit geology research are carried out for yingfengya lead-zinc deposit, focusing on the mineral composition and imbued characteristics of the deposit to determine the beneficial and harmful components and their occurrence state in the deposit.

Natural forest growth does not decrease water yield and forest responses to human disturbances and management interventions vary with ecosystem complexity, according to a global meta-analysis that includes 496 watersheds and spans 25 years.

The input and output torque testing is crucial for improving the quality of Industry robot reducers. In this study, the TMMISR and TMMOSR for a vertical-type robot reducer detector were designed. The length of measurement chain between the torque transducer and the tested reducer was shorten. The overall stiffness of this instrument has been improved through structural optimization. The characteristics of the two main parts of the torque-measurement errors were also analyzed. A high precision torque calibrator with a standard torque output is used to handle the torque calibration process. An error compensation method based on a backpropagation neural network was adopted for the error compensation process in this study. After error compensation, torque-measurement precision of 0.1% can be achieved by the reducer detector over the full torque measurement scale, and the instrument can be used for both static and dynamic measurements.

Abstract High‐quality perovskite single crystals (SCs) are emerging as promising optoelectronic materials and extensive photodetectors have been reported based on their SC frameworks, however, they are all disabled without applied external bias, and this is an evident obstacle for practical applications. Here, self‐powered photodetection (SPD) of perovskite SCs based on capacitance effects is reported when the capacitor releases its previously stored electric power by discharging operations. The capacitive results are highly in accord with numerical simulations of dielectrics, rather than the common ion migration. The lateral structures show good selectivity for local illuminations and consequently the induced self‐driven photovoltaic effects, but such influences on the SPD can be ignored when the capacitors are charged with sufficient electric power. This work first shows an attempt at achieving SPD in the form of lateral capacitors and may provide another new strategy for self‐powered perovskite devices.

BackgroundCuproptosis is a newly discovered form of cell death induced by targeting lipoacylated proteins involved in the tricarboxylic acid cycle. However, the roles of cuproptosis-related genes (CRGs) in the clinical outcomes and immune landscape of colon cancer remain unknown.MethodsWe performed bioinformatics analysis of the expression data of 13 CRGs identified from a previous study and clinical information of patients with colon cancer obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. Colon cancer cases were divided into two CRG clusters and prognosis-related differentially expressed genes. Patient data were separated into three corresponding distinct gene clusters, and the relationships between the risk score, patient prognosis, and immune landscape were analyzed. The identified molecular subtypes correlated with patient survival, immune cells, and immune functions. A prognostic signature based on five genes was identified, and the patients were divided into high- and low-risk groups based on the calculated risk score. A nomogram model for predicting patient survival was developed based on the risk score and other clinical features.ResultsThe high-risk group showed a worse prognosis, and the risk score was related to immune cell abundance, microsatellite instability, cancer stem cell index, checkpoint expression, immune escape, and response to chemotherapeutic drugs and immunotherapy. Findings related to the risk score were validated in the imvigor210 cohort of patients with metastatic urothelial cancer treated with anti-programmed cell death ligand 1.ConclusionWe demonstrated the potential of cuproptosis-based molecular subtypes and prognostic signatures for predicting patient survival and the tumor microenvironment in colon cancer. Our findings may improve the understanding of the role of cuproptosis in colon cancer and lead to the development of more effective treatment strategies.

Inoculation strategy is a significant determinant of the flavor quality of Zhenjiang aromatic vinegar. Herein, the comparative analyses of the effects of various inoculation strategies on the physicochemical properties, microbial community structure, and flavoring characteristics of Zhenjiang aromatic vinegar were performed. The results showed that the contents of total acid (6.91 g/100 g), organic acid (2099.63 ± 4.13 mg/100 g) and amino acid (3666.18 ± 14.40 mg/100 g) in the direct inoculation strategy were higher than those in the traditional inoculation strategy (6.21 ± 0.02 g/100 g, 1939.66 ± 4.16 mg/100 g and 3301.46 ± 13.41 mg/100 g). At the same time, it can effectively promote the production of acetoin. The diversity of strains under the traditional inoculation strategy was higher than that under the direct inoculation strategy, and the relative abundance of major microbial genera in the fermentation process was lower than that under the direct inoculation strategy. In addition, for two different inoculation strategies, pH was proved to be an important environmental factor affecting the microbial community structure during acetic acid fermentation. The correlation between main microbial species, organic acids, non-volatile acids, and volatile flavor compounds is more consistent. Therefore, this study may help to develop direct injection composite microbial inoculants to replace traditional starter cultures in future research.

Background and Aims:. Obeticholic acid (OCA) is a farnesoid X receptor agonist used in primary biliary cholangitis (PBC) treatment. Recent studies have expanded OCA use for NASH treatment and results from phase 3 clinical trial have shown beneficial reduction of ≥1 stage of fibrosis with no NASH worsening. However, safety concerns still preside, thus we systematically examine the safety profile of OCA in chronic liver disease. Materials and Methods:. A search was conducted in Medline and Embase databases for OCA randomized controlled trials in chronic liver disease. Binary events were pooled with Paule-Mandel random effects model and proportional events were examined in a generalized linear mixed model with Clopper-Pearson intervals. Results:. A total of 8 studies and 1878 patients were analyzed. There was a 75% [risk ratio (RR): 1.75, 95% CI: 1.43–2.15, p < 0.01] increased pruritis risk. OCA increased constipation incidence (RR: 1.88, 95% CI: 1.45–2.43, p < 0.01), decreased diarrhea (RR: 0.62, 95% CI: 0.50–0.77, p < 0.01), and increased development of hyperlipidemia (RR: 2.69, 95% CI: 1.85–3.92, p < 0.01) relative to placebo. Sensitivity analysis in NASH-only studies found a dose-dependent effect with pruritis which increases to RR: 3.07 (95% CI: 1.74–5.41) at 25 mg. However, up to 9.98% (95% CI: 5.01%–18.89%) of NAFLD patients with placebo similarly experience pruritis events. Overall, 16.55% (95% CI: 6.47%–36.24%) of patients with NAFLD on OCA experienced pruritis. There was no significant increase in cardiovascular events. Conclusions:. OCA may represent the first pharmacological treatment approved for NASH. However, pruritis, constipation, diarrhea, and hyperlipidemia were major events with evident dose-dependent effect that affect tolerability in NASH. Future long-term studies for longitudinal safety events are required.

Abstract Background Post-menopausal hypertension has been attributed solely to declining estrogen levels. The purpose of the research is to elucidate the mechanism by which follicle stimulating hormone(FSH) increases renin production involved in the regulation of blood pressure. Methods The expression of follicle stimulating hormone receptors (FSHRs) in renal juxtaglomerular cells and a As4.1 juxtaglomerular mouse cell line was evaluated. We established a mouse model by ovariectomy (OVX). Ovariectomized mice were treated with gonadotropin-releasing hormone agonist (GnRHa) (OVX + GnRHa). Ovariectomized mice initially received physiological doses of estrogen and were then injected with recombinant FSH (OVX + E + FSH). Results We found that FSHR was expressed in mouse renal juxtaglomerular cells labeled by renin antibody and in As4.1 cells. FSH promoted renin synthesis via Gsα-coupled FSHRs that activated protein kinase A, cyclic adenosine monophosphate(cAMP) response element-binding protein, extracellular signal-regulated kinase (Erk1/2), Protein kinase B(AKT), and c-Jun N-terminal kinase signaling pathways in As4.1 cells. We found increased serum FSH levels in the ovariectomized mouse with concurrent increases in renin, angiotensin II, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MAP). Additionally, increases in serum renin, angiotensin II, HR, SBP, DBP, and MAP were reduced by the additional injection of GnRHa. Exogenous FSH administration completely reversed decreases in renin, angiotensin II, HR, SBP, DBP, and MAP even in mice that received physiological doses of estrogen to maintain normal estradiol levels. Conclusions Elevated FSH stimulates renin production involving a mechanism that may be relevant to the expression of FSH receptors in renal juxtaglomerular cells.

When present in the cytosol, a variety of peptides encoded by the distal carboxyl-termini of the L-type CaV1 calcium channels downregulate channel activity and neurite outgrowth.

Abstract The receptor tyrosine kinases (RTKs) family is well-recognized as vital targets for the treatment of hepatocarcinoma cancer (HCC) clinically, whereas the survival benefit of target therapy sorafenib is not satisfactory for liver cancer patients due to metastasis. EGFR and MET are two molecules of the RTK family that were related to the survival time of liver cancer patients and resistance to targeted therapy in clinical reports. However, the mechanism and clinical therapeutic value of EGFR/MET in HCC metastasis are still not completely clarified. The study confirmed that EGFR/MET was highly expressed in HCC cells and tissues and the phosphorylation was stable after metastasis. The expression of EGFR/MET was up-regulated in circulating tumor microemboli (CTM) to accelerate IL-8 production and resistance to the lethal effect of leukocytes. Meanwhile, highly expressed EGFR/MET effectively regulated the Ras/MAPK pathway and stabilized suspended HCC cells by facilitating proliferation and inhibiting apoptosis. Moreover, EGFR/MET promoted phosphorylation of hetero-RTKs, which was dependent on high-energy phosphoric acid compounds rather than their direct interactions. In conclusion, highly expressed EGFR/MET could be used in CTM identification and suitable for preventing metastasis of HCC in clinical practice.

Background and objective In recent years, with the advancement of minimally invasive techniques, thoracoscopic thymoma resection has experienced a development process from three-port video-assisted thoracic surgery (VATS) to two-port (TP) and single-port (SP) variants. However, the feasibility and safety of SP-VATS have not been generally recognized. This study intends to explore the safety and feasibility of SP-VATS in thymoma resection, in order to provide a reference for clinical surgicalselection. Methods The clinical data of 197 patients who underwent thoracoscopic thymoma resection in Beijing Tongren Hospital from January 2018 to September 2021 were retrospectively analyzed. The patients were divided into SP-VATS group (n=42) and TP-VATS group (n=155). After matching propensity scores, there is no statistically significant difference in preoperative baseline data between SP-VATS group and TP-VATS group. Among them, there were 17 males and 25 females with an average age of 28-72 (48.00±9.43) years in the SP-VATS group, and 20 males and 22 females with an average age of 30-75 (50.38±9.83) years in TP-VATS group. The clinical effects of the two groups were compared. Results The operation was successfully completed in both groups, and there was no conversion to thoracotomy or increased surgical incisions. Compared with the TP-VATS group, the chest drainage time and hospital stay in the SP-VATS group were shorter [(2.95±0.76) d vs (3.33±0.85) d; (4.57±0.83) d vs (5.07±1.13) d], and the visual pain score at 24 h and 72 h after surgery were lower [(3.64±0.85) points vs (4.05±0.66) points; (2.33±0.75) points vs (3.07±0.68) points] (P0.05). Conclusion SP-VATS in thymoma is a safe, feasible, and less invasive procedure, with less postoperative pain and faster recovery than multi-port VATS.

Abstract Background Hashimoto’s thyroiditis (HT) is an autoimmune illness that renders individuals vulnerable to neuropsychopathology even in the euthyroid state, the mechanisms involved remain unclear. We hypothesized that activated microglia might disrupt synapses, resulting in cognitive disturbance in the context of euthyroid HT, and designed the present study to test this hypothesis. Methods Experimental HT model was induced by immunizing NOD mice with thyroglobulin and adjuvant twice. Morris Water Maze was measured to determine mice spatial learning and memory. The synaptic parameters such as the synaptic density, synaptic ultrastructure and synaptic-markers (SYN and PSD95) as well as the interactions of microglia with synapses were also determined. Results HT mice had poorer performance in Morris Water Maze than controls. Concurrently, HT resulted in a significant reduction in synapse density and ultrastructure damage, along with decreased synaptic puncta visualized by immunostaining with synaptophysin and PSD-95. In parallel, frontal activated microglia in euthyroid HT mice showed increased engulfment of PSD95 and EM revealed that the synaptic structures were visible within the microglia. These functional alterations in microglia corresponded to structural increases in their attachment to neuronal perikarya and a reduction in presynaptic terminals covering the neurons. Conclusion Our results provide initial evidence that HT can induce synaptic loss in the euthyroid state with deficits might be attributable to activated microglia, which may underlie the deleterious effects of HT on spatial learning and memory.

Expanded thermoplastic polyurethane (ETPU) foam materials with superelasticity for footwear application were developed and investigated. ETPU foams with different ratios of CO2/N2 as foaming agents and ETPU foams prepared by pure nitrogen foaming with different kinds of foaming additives were prepared by supercritical (Sc) foaming technology, which further made into sheet forms through the steam molding process. TPU foam exhibits better cell structure, crystallization performance, and mechanical strength with the increased CO2 proportion. Further, the foams using 25% CO2–75% N2 and 50% CO2–50% N2, showed a lower density and excellent resilience and cyclic-compression performance. However, an increase of N2 ratio improves the dimensional stability and compression set of the foam. The introduction of foaming aids enhances the interaction between Sc-N2 and TPU. The ETPU foam prepared under the same conditions has a smaller density and a larger expansion ratio. Especially the ETPU foam prepared by Sc-N2 using monofluorodichloroethane as the foaming assistant as a co-blowing agent, the decrease in cell size (from 117.9 to 19.6 μm) and density (from 0.175 to 0.139 g/cm3) has observed. The study revealed the high potential of these materials in footwear applications and offered sound evidence for mass production in the industry.

Applying the improved social-network analysis method and the idea of rolling-window regression, this paper explores the impact of an HSR network on the quality of urbanization and its dynamics. Based on a sample of 273 cities in China over the period 2009–2019, we find that the high-speed railway network has an increasingly positive effect on the quality of urbanization, which proves the existence of a network effect. The empirical results further show that this effect is closely related to the coverage rate of the high-speed rail network. In addition, heterogeneity analysis reveals that urban agglomeration cities are the main beneficiaries. Academically, our study provides a plausible explanation and evidence from network size differences for the two conflicting views of the HSR effect. Practically, we also propose some important policy implications for countries in different high-speed-rail-network construction stages.

Abstract Background RNA-cleaving deoxyribozymes (DNAzymes) are catalytic deoxyribonucleic acid molecules that have become a promising new class of gene suppressors by binding and cleaving target mRNA. This study investigated whether DNAzymes targeting Bcl-xL enhanced the effectiveness of radiotherapy and chemotherapy in colorectal cancer (CRC) cells. Methods Two types of CRC cells, SW480 and SW837, were transfected with five DNAzymes. Cell viability, Bcl-xL expression and apoptosis were examined. SW480 xenograft model was used to examine the combined effects of Bcl-xL DNAzymes and 5-FU (or X-rays) on tumor growth. Results Three Bcl-xL DNAzymes, DT882, DT883, and DT884 were identified to be effective in suppressing Bcl-xL expression and causing cell apoptosis. Furthermore, DT882 combined with 5-FU or radiotherapy addictively promoted cell apoptosis and significantly inhibited the growth of SW480 xenografts in vivo. Conclusions These results suggest that Bcl-xL DNAzymes can enhance the radiosensitivity and chemosensitivity in CRC cells via inducing apoptosis.

The frequent invasion of organisms poses a serious threat to biodiversity, ecosystem service functions, and economic development. Invasions from terrestrial systems have been well studied, but invasions from marine systems still lack a literature review, especially for invasive algae. With the frequent invasion of non-native algae, marine biodiversity and its sustainable use are threatened, and thus, the in-depth investigation of the biological mechanisms and ecological impacts of invasive alien marine algae has become particularly important. Here, we conducted a literature review of a series of studies that were undertaken by identified experts on algae invasions, including information on the classification of invasive algae in the ecosystem, mechanisms of invasion success (including the invader’s biological traits, interactions with native species, and adaptive evolution), and the impact on the native community and environment of the invaded area. In addition, we put forward suggestions for relevant research on invasive algae to overcome the current obstacles and provide references for future research on invasive marine algae. This review could be used to inform biological regulations and provides a scientific basis for the protection of marine biodiversity, sustainable environmental development, and the restoration of blue carbon ecosystems.

Background: Shifts in forest phenological events serve as strong indicators of climate change. However, the sensitivity of phenology events to climate change in relation to forest origins has received limited attention. Moreover, it is unknown whether forest phenology changes with the proximity to forest edge. Methods: This study examined the green-up dates, dormancy dates, time-integrated NDVI (LiNDVI, a measure of vegetation productivity in growing season), and their sensitivities to climatic factors along the gradients of distance (i.e. proximity) to forest edge (0–2 ​km) in China's natural forests (NF) and planted forests (PF). For the analysis, field-surveyed data were integrated with Moderate Resolution Imaging Spectroradiometer (MODIS) NDVI from 2000 to 2022. Results: Our results reveal that PF had earlier green-up dates, later dormancy dates, and higher LiNDVI than NF. However, green-up sensitivities to temperature were higher at the edges of NF, whereas no such pattern was observed in PF. Conversely, the sensitivity of dormancy dates remains relatively stable from the inner to the edge of both NF and PF, except for a quadratic change in dormancy date sensitivity to precipitation found in NF. Additionally, we found that the green-up sensitivity to temperature increased with decreasing proximity to edge in NF evergreen forests, while it showed the opposite trend in PF evergreen forests. Furthermore, we observed that the precipitation impact on green-up dates shifts from postponing to advancing from the inner to the edge of NF, whereas precipitation dominantly postpones PF's green-up dates regardless of the proximity to edge. The LiNDVI exhibits higher sensitivity to precipitation at the edge areas, a phenomenon observed in NF but not in PF. Conclusions: These results suggest that the responses of forests to climate change vary with the distance to the edge. With increasing edge forests, which results from fragmentation caused by global changes, we anticipate that desynchronized phenological events along the distance to the edge could alter biogeochemical cycles and reshape ecosystem services such as energy flows, pollination duration, and the tourism industry. Therefore, we advocate for further investigations of edge effects to improve ecosystem modelling, enhance forest stability, and promote sustainable tourism.

This paper proposes a wearable flexible dual-band antenna that covers the 2.34–2.68 GHz and 4.05–5.26 GHz frequency bands. This antenna employs a novel nested imitation annular solar eclipse structure, where the main radiator is a gradually widening loop, and another loop is coupled inside the radiator. The antenna, with overall dimensions of 40∗32∗0.3 mm³, utilizes polyimide as the dielectric material. The gain, efficiency, and cross-polarization of the antenna were tested using a microwave anechoic chamber. The antenna achieves a maximum gain of 6 dBi and a maximum efficiency of 79.6%. We tested the SAR of the antenna at 10 mm from the human body, which was significantly below the international standard of 2.0 W/kg. The flexible antenna presented in this paper exhibits a broad low-frequency bandwidth, enabling coverage of various communication bands such as ISM, WLAN, WIMAX, and Bluetooth. The antenna delivers satisfactory simulation and measurement results while meeting the requirements of minimizing radiation exposure to the human body.