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Abstract Background Ferroptosis, characterized by iron-dependent lipid peroxidation, emerges as a promising avenue for hepatocellular carcinoma (HCC) intervention due to its tumor susceptibility. RNA N6-methyladenosine (m6A) modification has been involved in several types of regulated cell death. However, the roles and molecular mechanisms of m6A-related regulators in HCC cell ferroptosis remain unclear. Methods By examining a series of m6A modification enzymes upon ferroptosis induction or inhibition, we identified METTL16 as a novel ferroptotic repressor in HCC cells. The roles of METTL16 on ferroptosis and HCC development were investigated in multiple cell lines, human HCC organoids, subcutaneous xenografts and MYC/Trp53−/− HCC model in hepatocyte-specific Mettl16 knockout and overexpression mice. The underlying mechanism was elucidated with MeRIP/RIP-qPCR, luciferase assay, Co-IP assay and Mass Spectrometry. The clinical significance and relevance were evaluated in human samples. Results High METTL16 expression confers ferroptosis resistance in HCC cells and mouse models, and promotes cell viability and tumor progression. Mechanistically, METTL16 collaborates with IGF2BP2 to modulate SENP3 mRNA stability in an m6A-dependent manner, and the latter impedes the proteasome-mediated ubiquitination degradation of Lactotransferrin (LTF) via de-SUMOylation. Elevated LTF expression facilitates the chelation of free iron and reduces liable iron pool level. SENP3 and LTF are implicated in METTL16-mediated HCC progression and anti-ferroptotic effects both in vivo and in vitro. Clinically, METTL16 and SENP3 expression were positively correlated, and high METTL16 and SENP3 expression predicts poor prognosis in human HCC samples. Conclusions Our study reveals a new METTL16-SENP3-LTF signaling axis regulating ferroptosis and driving HCC development. Targeting this axis is a promising strategy for sensitizing ferroptosis and against HCC.

Abstract Organic molecules with dynamic covalent-bonding characteristics have attracted much attention for their important role in constructing stimulus-responsive smart materials. However, it is difficult to realize sensitive and reversible covalent bond cleavage/formation through external stimuli in the aggregated state of molecules. Herein, a series of 2,3-diphenylmaleonitriles (DPMNs) with photoinduced π-bond cleavage properties have been designed and synthesized to construct the dynamic covalent bond materials. The cis-form 2,3-diphenylmaleonitriles (Z-DPMNs) exhibit significant photochromism in both solid and solution states under ultraviolet light and visible light. The photochromism stems from the photoinduced π-bond splitting of Z-DPMNs, resulting in a transition from the closed-shell to open-shell structure. Moreover, the twisted structure and molecular stacking of Z-DPMNs, the push-pull electron effect of substituents, and the external factors including temperature and solvent polarity have important effects on the dynamic conversion of π-bonds. Based on the sensitive and reversible optical performance transformation, Z-DPMNs can be applied as safety ink in anti-counterfeiting, information encryption and storage systems. This work not only provides an approach for constructing dynamic covalent bonds but also greatly enriches stimulus-responsive materials.

The complete chloroplast genome sequence of Sassafras randaiense (Hayata) Rehder, 1920, a subtropical tree in the family Lauraceae, was determined. For a better understanding of the differences between S. randaiense and S. tzumu, the complete chloroplast genome of S. randaiense was sequenced and analyzed. The complete chloroplast genome is 151,781 bp in length, consisting of a pair of inverted repeat (IR) regions of 20,114 bp, one large single-copy (LSC) region of 92,740 bp, and one small single-copy (SSC) region of 18,813 bp. The overall GC content of the complete chloroplast genome is 39.2%. Further, maximum-likelihood phylogenetic analysis was conducted using 31 complete plastome sequences, which support that S. randaiense and S. tzumu are nested among the members of Cinnamomum, suggesting that Sassafras belongs to Cinnamomum.

Scrub root systems play a crucial role in preventing soil erosion and nutrient loss. However, the effects of the root system configuration on soil nutrient dynamics and microbial changes at various evolutionary stages remain poorly understood. In this study, we investigated the relationship between soil physical and chemical properties and the diversity of bacteria and fungi throughout the evolutionary stages of the scrub root systems. This was achieved through a combination of whole-root excavation and root tracing techniques. The results indicated that root diameter was the main factor contributing to the continuous increase in carbon (C): phosphorus (P) and nitrogen (N): P ratios as the scrub sand pile developed. The soil organic carbon (SOC), total soil nitrogen (TN), and total soil phosphorus (TP) contents in the soil in the four evolutionary stages were the highest during the developmental stage, but the change in TP content was not statistically significant (P > 0.05). Partial least squares path modeling and redundancy analysis (RDA) indicated that root system stoichiometric C and N contents were positively correlated with microbial diversity (R2 = 0.85). There was no correlation between the evolutionary stage and soil nutrient TN, whereas soil nutrient TN was negatively correlated with microbial diversity (R2 = −0.92). These findings elucidate the relationship between the evolutionary stage of root chemical measurement characteristics, soil elements and microorganisms, and their subsequent effects on root elemental composition and microbial diversity. This study enhances the current understanding of plant–soil interactions in desert steppe ecosystems.

The implementation of Salix psammophila sand barriers measures constitutes a crucial element in desertification control, providing a solid theoretical foundation for the future application and pretreatment of sand barriers in production practices. To address the specific damage types predominant in desert environments, we executed simulations of ultraviolet irradiation and rainfall phenomena on mechanical sand barriers in sandy areas and also inspected the variations in chemical properties during accelerated aging processes. The findings unequivocally demonstrate that: (1) The synergistic impact of ultraviolet irradiation and water accelerated the deformation and fracturing of the S.psammophila sand barriers, thereby causing a partial degradation of its chemical properties and conspicuous lignin oxidation; (2) The fissure of the sand barrier deepened, resulting in structural alterations. The existence of water expedites the degradation process of S.psammophila sand barriers under ultraviolet irradiation. (3)With respect to the binding form of C atoms, the carbon atoms at S.psammophila sand barriers were highly oxidized after 576 hours of accelerated aging. The components of C2 (C-O) and C3 (C=O) rising to 40.16% and 12.24% respectively, while the components of C1 (C-C) declined to 47.60%. The amount of hydroxyl (O-C-O), carbonyl (C=O), and carboxyl (O-C=O) groups increases in line with the expansion of the contact area between the sand barrier structure and ultraviolet irradiation as well as water. More free radical substances are generated, thereby causing the chemical binding properties to tend to be more stable. In summary, Ultraviolet irradiation and water change are the primary factors influencing the degradation of S.psammophila sand barriers material structure and properties. In future desertification control, it is imperative to focus on enhancing the longevity of sand barriers by ensuring their waterproofing capabilities and resistance to ultraviolet irradiation.

Rationale and objectives: To predict high-risk prostate cancer (PCa) by combining the habitat features of biparametric magnetic resonance imaging (bp-MRI) with the omics features of contrast-enhanced ultrasound (CEUS). Materials and methods: This study retrospectively collected patients with PCa confirmed by histopathology from January 2020 to June 2023. All patients underwent bp-MRI and CEUS of the prostate, followed by a targeted and transrectal systematic prostate biopsy. The cases were divided into the intermediate-low-risk group (Gleason score ≤7, n = 59) and high-risk group (Gleason score ≥8, n = 33). Radiomics prediction models, namely, MRI_habitat, CEUS_intra, and MRI-CEUS models, were developed based on the habitat features of bp-MRI, the omics features of CEUS, and a merge of features of the two, respectively. Predicted probabilities, called radscores, were then obtained. Clinical-radiological indicators were screened to construct clinic models, which generated clinic scores. The omics–clinic model was constructed by combining the radscore of MRI-CEUS and the clinic score. The predictive performance of all the models was evaluated using the receiver operating characteristic curve. Results: The area under the curve (AUC) values of the MRI-CEUS model were 0.875 and 0.842 in the training set and test set, respectively, which were higher than those of the MR_habitat (training set: 0.846, test set: 0.813), CEUS_intra (training set: 0.801, test set: 0.743), and clinic models (training set: 0.722, test set: 0.611). The omics–clinic model achieved a higher AUC (train set: 0.986, test set: 0.898). Conclusions: The combination of the habitat features of bp-MRI and the omics features of CEUS can help predict high-risk PCa.

Salix psammophila sand barriers degrade under sunlight exposure, resulting in diminished protective performance and shortened service life in desertification control. To address the unresolved issue of photoinduced damage and degradation in sand barriers, we conducted simulations to assess the accelerated damage effect of ultraviolet (UV) rays during solar exposure of S. psammophila sand barriers. Our analysis focused on elucidating the mechanism of UV irradiation in sand barriers by examining the structural and material property changes that occur during the degradation process. The results indicated the following: (1) The discoloration of sand barriers resulting from UV irradiation was primarily ascribed to the modification in lignin content. (2) The morphology and protective performance of S. psammophila sand barriers underwent significant changes following exposure to UV irradiation. The 96-day and 144-day time points of UV exposure are crucial for evaluating the extent of UV degradation in sand barriers. After 192 days of UV irradiation, there was a decrease in mass loss percentage by 3.62%, modulus of elasticity by 8.63%, and modulus of rupture by 6.74%. (3) The lignin, hemicellulose, and cellulose content decreased by 23.12%, 14.30%, and 6.96%, respectively. The impact of UV irradiation on the polysaccharide (cellulose and hemicellulose) in S. psammophila sand barriers was relatively minimal. (4) The carbon binding form in S. psammophila sand barriers underwent a transformation, characterized by a significant decrease in C1 content and an increase in C2 and C3 content. This resulted in a gradual enhancement of the oxidation state and binding energy of carbon. Therefore, to prolong the utilization lifespan of S. psammophila sand barriers, it is essential to address the UV irradiation behavior from the perspective of inhibiting lignin reactions.

Abstract Acute lung injury (ALI) is life-threatening. MicroRNAs (miRNAs) are often abnormally expressed in inflammatory diseases and are closely associated with ALI. This study investigates whether miRNA-206-3p attenuates pyroptosis in ALI and elucidates the underlying molecular mechanisms. ALI mouse and cell models were established through lipopolysaccharide (LPS) treatment for 24 h. Subsequently, the models were evaluated based on ultrasonography, the lung tissue wet/dry (W/D) ratio, pathological section assessment, electron microscopy, and western blotting. Pyroptosis in RAW264.7 cells was then assessed via electron microscopy, immunofluorescence, and western blotting. Additionally, the regulatory relationship between miRNA-206-3p and the Toll-like receptor (TLR)4/nuclear factor (NF)-κB/Nod-like receptor protein-3 (NLRP3) pathway was verified. Finally, luciferase reporter gene and RNA pull-down assays were used to verify the targeting relationship between miRNA-206-3p and TLR4. miRNA206-3p levels are significantly decreased in the LPS-induced ALI model. Overexpression of miRNA-206-3p improves ALI, manifested as improved lung ultrasound, improved pathological changes of lung tissue, reduced W/D ratio of lung tissue, release of inflammatory factors in lung tissue, and reduced pyroptosis. Furthermore, overexpression of miRNA-206-3p contributed to reversing the ALI-promoting effect of LPS by hindering TLR4, myeloid differentiation primary response 88 (MyD88), NF-κB, and NLRP3 expression. In fact, miRNA-206-3p binds directly to TLR4. In conclusion, miRNA-206-3p alleviates LPS-induced ALI by inhibiting inflammation and pyroptosis via TLR4/NF-κB/NLRP3 pathway modulation.

Abstract Background Marfan syndrome (MFS) is an autosomal dominant connective tissue disease with wide clinical heterogeneity, and mainly caused by pathogenic variants in fibrillin-1 (FBN1). Methods A Chinese 4-generation MFS pedigree with 16 family members was recruited and exome sequencing (ES) was performed in the proband. Transcript analysis (patient RNA and minigene assays) and in silico structural analysis were used to determine the pathogenicity of the variant. In addition, germline mosaicism in family member (Ι:1) was assessed using quantitative fluorescent polymerase chain reaction (QF-PCR) and short tandem repeat PCR (STR) analyses. Results Two cis-compound benign intronic variants of FBN1 (c.3464–4 A > G and c.3464-5G > A) were identified in the proband by ES. As a compound variant, c.3464-5_3464-4delGAinsAG was found to be pathogenic and co-segregated with MFS. RNA studies indicated that aberrant transcripts were found only in patients and mutant-type clones. The variant c.3464-5_3464-4delGAinsAG caused erroneous integration of a 3 bp sequence into intron 28 and resulted in the insertion of one amino acid in the protein sequence (p.Ile1154_Asp1155insAla). Structural analyses suggested that p.Ile1154_Asp1155insAla affected the protein’s secondary structure by interfering with one disulfide bond between Cys1140 and Cys1153 and causing the extension of an anti-parallel β sheet in the calcium-binding epidermal growth factor-like (cbEGF)13 domain. In addition, the asymptomatic family member Ι:1 was deduced to be a gonadal mosaic as assessed by inconsistent results of sequencing and STR analysis. Conclusions To our knowledge, FBN1 c.3464-5_3464-4delGAinsAG is the first identified pathogenic intronic indel variant affecting non-canonical splice sites in this gene. Our study reinforces the importance of assessing the pathogenic role of intronic variants at the mRNA level, with structural analysis, and the occurrence of mosaicism.

Species in the Amorphophallus genus are important cash crops in many tropical and subtropical Asian countries. Although several molecular markers have been employed to determine relationships and assess genetic variation in the Amorphophallus genus, some conflicts remain in infrageneric classification and evolution. To aid in the phylogenetic research of the Amorphophallus genus, we collected one sample of Amorphophallus tonkinensis Engler and Gehrmann 1911 from southwestern China. We assembled the first chloroplast genome of this species using high-throughput sequencing. The assembled genome was 169,341 bp long with a typical quadripartite structure (GenBank accession number: PP234804). The lengths of the large single-copy region, small single-copy region, and two inverted repeats were 90,705 bp, 15,640 bp, 31,498 bp, and 31,498 bp, respectively. We annotated 129 genes across the chloroplast genome of A. tonkinensis. The phylogenetic trees suggested that the Amorphophallus species distributed in continental Asia split into two main clades. The chloroplast genome reported in our study provided valuable genomic resources for the future phylogenetic research of the Amorphophallus genus.

Abstract Mud loss is the most serious formation damage in oil and gas well drilling engineering and is an unsolved technical problem. To prevent mud loss, it is necessary to accurately understand and identify three key factors of mud loss, including the location of the loss, the time of occurrence, and the severity of the loss. The diagnosis of mud loss is a prerequisite for the proper formulation of mud loss control techniques. It emphasizes the integration of predrilling, drilling, and postanalysis information to describe and characterize loss zones and predict potential loss zones. On the basis of the theory of engineering fuzzy mathematics, we develop a mathematical model for loss probability evaluation that combines logging anomaly features and engineering data to predict the location of losses from drilling mud and develop a loss formation identification method. The study of hydraulic fracture deformation through stress‐sensitive experiments and numerical simulations can predict the deformation and severity of loss channels, which can help optimize the loss of circulating material by adding drilling fluid. Loss pressure models have been developed based on mud loss mechanisms, and loss pressure for hydraulic fracture creation, connection, and extension has been studied to help identify loss mechanisms and types. Mud losses can be identified by unusual engineering characteristics, including sudden changes in drilling times, cuttings, and mud logging. Real‐time logging parameters can be used to monitor the loss process and hence predict the loss trend. The framework of loss diagnosis techniques is established, which helps in successful mud loss controlling.

AbstractThe mountainous region of southern China has been characterized by its complicated environment and topography. Amorphophallus kiusianus Makino 1913 is a representative species of extreme habitat preference that resides mainly in this region. To help study the genetic differentiation mechanisms of A. kiusianus populations, we sequenced the first chloroplast genome of this species using next-generation sequencing. The chloroplast genome was 166,269 bp in length with an average GC content of 36% (GenBank accession number: PP072243). The lengths of the large single-copy region (LSC), small single-copy region (SSC), and two inverted repeats (IRs) were 90,701 bp, 14,802 bp, 31,383 bp, and 31,383 bp, respectively. One hundred and twenty-nine genes were annotated in the chloroplast genome, including 84 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. The phylogenetic tree suggested a close relationship among A. kiusianus, A. yunnanensis, and A. coaetaneus. The chloroplast genome reported in this study provides valuable genomic resources for the future phylogeographic research of A. kiusianus.

AbstractCastanopsis orthacantha Franch. 1899 is one representative tree species distributed in the evergreen broad-leaved forests of southwestern China. This species is an important source of timber for manufacturing furniture, floors, and paper. It also plays a significant role in maintaining ecological balance and stability. To help with the genetic diversity assessment of C. orthacantha, we sequenced and assembled the first complete chloroplast genome. The length of the chloroplast genome was 160,588 bp, with a typical quadripartite structure (GenBank accession no. OR900101). The large single-copy (LSC), small single-copy (SSC), and two inverted repeats (IRs) were 90,237 bp, 18,953 bp, and 25,699 bp in length, respectively. We annotated one hundred and thirty genes across the chloroplast genome, including 86 protein-coding genes (79 are unique), 37 tRNA genes (29 are unique), and eight rRNA genes (four are unique). Seventeen genes had one intron, and four were detected with two introns. The maximum likelihood phylogeny suggested that C. orthacantha, C. lamontii, C. sclerophylla, and C. hainanensis formed a clade with a high bootstrap value. This newly sequenced chloroplast genome assembly will aid in the population genetic and phylogenetic studies of Castanopsis species in the future.

AbstractKonjac glucomannan consists of D-mannose and D-glucose units and is a hydrocolloid obtained from the corm of Amorphophallus species. Due to its bioactive properties, biodegradability, and hydrophilic ability, glucomannan is widely used in the fields of food, medicine, and industry. Amorphophallus species have been cultivated as cash crops in many Asian countries. Amorphophallus kachinensis Engler & Gehrmann 1911 is naturally distributed in southwestern China, Laos, and northern Thailand. To help the genetic assessment and conservation of this species, the first chloroplast genome of A. kachinensis was sequenced on the Illumina sequencing platform. We assembled the chloroplast genome using the software GetOrganelle and annotated the genome by Geseq and Cpgavas 2. The assembled chloroplast genome was 173,330 bp long, and the average GC content was 35% (GenBank accession number: PP072244). The chloroplast genome of A. kachinensis contained one large single copy, one small single copy, and two inverted repeats, with lengths of 92,030 bp, 15,118 bp, 33,091 bp, and 33,091 bp, respectively. We successfully annotated 132 genes across the genome, which was consistent with other Amorphophallus species. The phylogenetic tree indicates a sub-divergence in the Amorphophallus genus with two main genetic groups detected among eight species. The two genetic groups should be treated as distinct evolutionarily significant units when making conservation strategies. Our study enriched the chloroplast genome resources of the Amorphophallus genus and could help future phylogeographic studies, protection, and utilization of wild resources.

Abstract As testicular mesenchymal stromal cells, stem Leydig cells (SLCs) show great promise in the treatment of male hypogonadism. The therapeutic functions of mesenchymal stromal cells are largely determined by their reciprocal regulation by immune responses. However, the immunoregulatory properties of SLCs remain unclear. Here, we observe that SLCs transplantation restore male fertility and testosterone production in an ischemia‒reperfusion injury mouse model. SLCs prevent inflammatory cascades through mitochondrial transfer to macrophages. Reactive oxygen species (ROS) released from activated macrophages inducing mitochondrial transfer from SLCs to macrophages in a transient receptor potential cation channel subfamily member 7 (TRPM7)-mediated manner. Notably, knockdown of TRPM7 in transplanted SLCs compromised therapeutic outcomes in both testicular ischemia‒reperfusion and testicular aging mouse models. These findings reveal a new mechanism of SLCs transplantation that may contribute to preserve testis function in male patients with hypogonadism related to immune disorders.

Accurately predicting travel destinations in a city from partial trajectories is crucial for many location-based services. This task faces two challenges: data sparsity and the complex probability distribution of destinations. Previous studies neglected the fusion of spatiotemporal features and urban contexts, which limited their effectiveness in characterizing trajectory patterns and exacerbated data sparsity issues. Most methods either predicted a single destination or the probability of each predefined sub-region, but they struggled with the modifiable areal unit problem. To address these problems, we propose an approach based on the diffusion probabilistic model, comprising a trajectory encoder and a diffusion decoder. The trajectory encoder extracts four embeddings to represent spatiotemporal features and urban contexts, integrating them using an attention mechanism to mitigate data sparsity. The diffusion decoder recovers the complex destination probability distribution and predicts multiple candidate destinations without predefined regional units, effectively addressing the modifiable areal unit problem. Experiments on driving trajectories in Shenzhen, China, show an average improvement of 10.80% across four metrics compared to state-of-the-art methods. We also observed the influence of trajectory length and origin location on prediction accuracy. The results validate the importance of modeling destination probability distributions, as well as integrating spatiotemporal features and urban contexts.

Background This study aims to evaluate the clinical application value of ultrasound viscoelastic imaging in noninvasive quantitative assessment of chronic kidney disease (CKD).Methods A total of 332 patients with CKD and 190 healthy adults as a control group were prospectively enrolled. Before kidney biopsy, ultrasound viscoelastic imaging was performed to measure the mean stiffness value (Emean), mean viscosity coefficient (Vmean), and mean dispersion coefficient (Dmean) of the renal. CKD patients were divided into three groups based on estimated glomerular filtration rate. The differences in clinic, pathology, ultrasound image parameters between the control and patient groups, or among different CKD groups were compared. The correlation between viscoelastic parameters and pathology were analyzed.Results Emean, Vmean, and Dmean in the control group were less than the CKD group (p 6.61 kPa, Vmean > 1.86 Pa·s, or Dmean > 7.51 m/s/kHz may suggest renal dysfunction. Combining Vmean, Dmean, and Emean can improve the efficiency of identifying CKD.

ABSTRACTEukaryotic gene expression is regulated by RNA interference (RNAi). Dicer-like (DCL), Argonaute (AGO), and RNA-dependent RNA polymerase (RDR) are essential elements involved in the process of RNAi. However, Jatropha (J.) curcas, an oil-producing plant, has not undergone any previous systematic analysis or expression profiling of these genes. In this study, a total of four JcDCL, nine JcAGO, and seven JcRDR genes were identified in the J. curcas genome. Based on phylogenetic analysis, each gene family was classified into four clades and randomly distributed on nine J. curcas chromosomes. Protein sequence alignment revealed that the classical PAZ, Piwi, and RdRP domains were present in all JcDCLs, JcAGOs, and JcRDRs, respectively. Comprehensive expression pattern analysis using RNA-seq data showed various expression patterns in different organs and under different abiotic stresses. In addition, special attention should be paid to JcDCL1, JcAGO1, JcAGO4, and JcRDR5, which play important roles in response to various stresses.

In order to explore the effects of two plants on the spatial distribution and nutrient distribution of crusts in different directions and distances after 30 years of aerial seeding, as well as the relationship between crust thickness and nutrient content, this paper takes the aerial seeding afforestation area in the northeastern margin of Tengger Desert as the research area, and the crusts under the plants of Hedysarum scoparium and Calligonum mongolicum as the research objects. The distribution of crust thickness and nutrients was analyzed, and the relationship between them was constructed. The thickness of the crust of H. scoparium and C. mongolicum was the largest in the southeast direction and the smallest in the northwest direction. With increasing distance from the plant, it shows a significant decreasing trend. The crust thickness of H. scoparium was higher than that of C. mongolicum. The nutrient indexes in the southeast direction of the crust of H. scoparium and C. mongolicum were significantly higher than those in the northwest direction; With the increase of the distance from the root of the plant, the nutrient content showed a significant decreasing trend. The contents of organic matter and available nitrogen in the crust of C. mongolicum were higher than those of H. scoparium, and the contents of available potassium and available phosphorus were lower than those of H. scoparium. The trend of nutrient enrichment rate of the crusts of the two plants was consistent with the trend of nutrient distribution. There was a significant positive correlation between the crust thickness and nutrients in the four directions under C. mongolicum. There was a significant positive correlation between the crust thickness and nutrients in the southwest direction under H. scoparium. The changes of available nitrogen, available phosphorus, available potassium and organic matter content in the crust under H. scoparium can explain 52.5% of the change of its thickness. The changes of available nitrogen, available phosphorus, available potassium and organic matter content in the crust under C. mongolicum can explain 78.5% of the change of its thickness. After 30 years of aerial seeding in Tengger Desert, the thickness and nutrients of the crust in the southeast direction of H. scoparium and C. mongolicum were significantly higher than those in the northwest direction and showed a decreasing trend with the increase of distance from the root of the plant. There was a positive correlation between crust nutrient and thickness.

The physiological activity facilitated by arbuscular mycorrhizal fungi (AMF) contributes to plants’ ability to tolerate drought. Nevertheless, it is unclear if AMF colonization affects the expression of genes in the host plant that encode antioxidant enzymes in the superoxide dismutase (SOD) family, which help alleviate drought stress in plants. Here, we conducted a pot trial to determine whether colonization by the AMF Rhizophagus irregularis improves drought resistance in Bombax ceiba. We comprehensively analyzed the SOD gene family and evaluated genome-wide expression patterns of SODs and SOD activity in AMF-colonized and non-mycorrhizal plants under simulated drought. We identified a total of 13 SODs in the genome of B. ceiba, including three FeSODs (BcFSDs), three MnSODs (BcMSDs), and seven Cu/ZnSODs (BcCSDs). Phylogenetic analysis based on binding domain revealed that SOD genes from B. ceiba and various other plant species can be divided into three separate groups, showing significant bootstrap values. Our examination of gene composition and patterns suggests that most BcSOD genes in these three subgroups are significantly conserved. Additionally, it was noted that hormones and stress-responsive cis-regulatory elements were found in all BcSOD promoters. Expression profiling by qRT-PCR demonstrated that AMF increased relative expression levels of Cu/Zn-SODs in both roots and shoots under drought stress, except for BcCSD3 in roots. Furthermore, AMF colonization increased the relative expression of BcMSD1a and BcMSD1b in roots, augmenting SOD activities and increasing ROS scavenging during drought. In general, this work offers molecular evidence in support of the beneficial effect of AMF colonization on drought tolerance in B. ceiba. It also elucidates the expression patterns of SOD genes, which will support efforts to optimize mycorrhizal seedling cultivation under stressful conditions.

Solid-state batteries (SSBs) have received widespread attention with their high safety and high energy density characteristics. However, solid-solid contacts in the internal electrode material and the electrode material/solid electrolyte (SE) interfaces, as well as the severe electrochemo-mechanical effects caused by the internal stress due to the volume change of the active material, these problems hinder ion/electron transport within the SSBs, which significantly deteriorates the electrochemical performance. Applying fabrication pressures and stack pressures are effective measures to improve solid-solid contact and solve electrochemo-mechanical problems. Herein, the influences of different pressures on cathode material, anode material, SEs, and electrode/SEs interface are briefly summarized from the perspective of interface ion diffusion, transmission of electrons and ions in internal particles, current density and ion diffusion kinetics, and the volume changes of Li+ stripping/plating based on two physical contact models, and point out the direction for the future research direction of SSBs and advancing industrialization by building the relationship between pressures and SSBs electrochemistry.

This study investigated airflow changes and sediment transport in the blowouts of the sandy grassland in Xilingol, Inner Mongolia. The results show that the wind direction inside the blowout is influenced by the direction of the incoming wind. Specifically, when the angle between the incoming wind direction and the long axis of the blowout is less than 15°, both sides of the wall tend to generate a wind flow towards the east exit. Meanwhile, the main airflow along the central axis airflow deflects towards the north side wall. However, when the angle is greater than 15°, the airflow on the north wall first disperses and then converges towards the wellbore. Conversely, the airflow on the south wall blows out in a southeast direction, and the axial airflow deflects towards the south wall. The rate of wind speed acceleration on both sides of the wall increases with height within the blowout but decreases along the central axis section. Higher wind speeds correlate with greater cumulative sand transport heights. Sand transport heights on both sides of the deflation basin are smaller than those along the central axis section, with the opposite observed in the depositional lobe. The rate of sand transport is primarily influenced by wind direction and wind speed, followed by, topography, vegetation coverage, slope, and aspect. These variations in airflow, combined with sediment transport, lead to the blowout taking on a develop deeper, longer, and wider shape.

Abstract Developing high‐efficiency and stable bifunctional electrocatalysts for water splitting remains a great challenge. Herein, NiMoO4 nanowires as sacrificial templates to synthesize Mo‐doped NiFe Prussian blue analogs are employed, which can be easily phosphorized to Mo‐doped Fe2xNi2(1‐x)P nanotubes (Mo‐FeNiP NTs). This synthesis method enables the controlled etching of NiMoO4 nanowires that results in a unique hollow nanotube architecture. As a bifunctional catalyst, the Mo‐FeNiP NTs present lower overpotential and Tafel slope of 151.3 (232.6) mV at 100 mA cm−2 and 76.2 (64.7) mV dec−1 for HER (OER), respectively. Additionally, it only requires an ultralow cell voltage of 1.47 V to achieve 10 mA cm−2 for overall water splitting and can steadily operate for 200 h at 100 mA cm−2. First‐principles calculations demonstrate that Mo doping can effectively adjust the electron redistribution of the Ni hollow sites to optimize the hydrogen adsorption‐free energy for HER. Besides, in situ Raman characterization reveals the dissolving of doped Mo can promote a rapid surface reconstruction on Mo‐FeNiP NTs to dynamically stable (Fe)Ni‐oxyhydroxide layers, serving as the actual active species for OER. The work proposes a rational approach addressed by electron manipulation and surface reconstruction of bimetallic phosphides to regulate both the HER and OER activity.

Abstract Integrating multiple single‐cell datasets is essential for the comprehensive understanding of cell heterogeneity. Batch effect is the undesired systematic variations among technologies or experimental laboratories that distort biological signals and hinder the integration of single‐cell datasets. However, existing methods typically rely on a selected dataset as a reference, leading to inconsistent integration performance using different references, or embed cells into uninterpretable low‐dimensional feature space. To overcome these limitations, a reference‐free method, Beaconet, for integrating multiple single‐cell transcriptomic datasets in original molecular space by aligning the global distribution of each batch using an adversarial correction network is presented. Through extensive comparisons with 13 state‐of‐the‐art methods, it is demonstrated that Beaconet can effectively remove batch effect while preserving biological variations and is superior to existing unsupervised methods using all possible references in overall performance. Furthermore, Beaconet performs integration in the original molecular feature space, enabling the characterization of cell types and downstream differential expression analysis directly using integrated data with gene‐expression features. Additionally, when applying to large‐scale atlas data integration, Beaconet shows notable advantages in both time‐ and space‐efficiencies. In summary, Beaconet serves as an effective and efficient batch effect removal tool that can facilitate the integration of single‐cell datasets in a reference‐free and molecular feature‐preserved mode.

Abstract Background Hepatocellular carcinoma (HCC) is the most common type of malignant liver tumor with poor prognosis. In this study, we investigated the expression of transforming growth factor beta regulator 4 (TBRG4) in HCC and its effects on the proliferation, invasion, and metastasis of HCC cells, and analyzed the possible molecular mechanisms. Method Downloading the expression and clinical information of HCC samples in the TCGA database, analyzing the expression differences of TBRG4 by bioinformatics methods, analyzing the clinical relevance and prognostic significance. Performing GO, KEGG and GSEA enrichment analysis on the TBRG4-related gene set in patient HCC tissues. Applying cell counting, scratch test and Transwell experiment to study the biological function of TBRG4 in HCC. Mitochondrial membrane potential, apoptosis and ROS levels were evaluated to assess cell iron death. Western blot, RT-PCR, laser confocal microscopy and co-immunoprecipitation were used to detect and analyze the downstream signaling pathways and interacting molecules of TBRG4. Results Bioinformatics analysis revealed that TBRG4 was abnormally highly expressed in HCC tumor tissues and was associated with poor prognosis and metastasis in HCC patients. GO and KEGG functional enrichment analysis showed that TBRG4 was related to oxidative stress and NADH dehydrogenase (ubiquinone) activity. GSEA enrichment analysis showed that TBRG4 was associated with Beta catenin independent wnt signaling and B cell receptor. Functional experiments confirmed that knocking down TBRG4 could inhibit the proliferation, migration, and invasion of HCC cells. Mechanistically, TBRG4 inhibited the function of HCC cells through the DDX56/p-AKT/GSK3β signaling pathway. In addition, interference with TBRG4 expression could reduce the mitochondrial membrane potential and accumulate ROS in HCC cells, leading to increased ferroptosis. Co-IP analysis showed that TBRG4 specifically bound to Beclin1. Conclusion TBRG4 is highly expressed in HCC tumor tissues and is associated with poor prognosis. It may regulate the proliferation, invasion, and metastasis of HCC cells through the DDX56/p-AKT/GSK3β signaling pathway. TBRG4 may interact with Beclin1 to regulate the ferroptosis of HCC cells.

Abstract This study aimed to reveal the soil reinforcement by shrub root systems after repeated stress from external forces, such as high winds and runoff, for extended periods in the wind-hydraulic compound erosion zone. Using the widely distributed Shandong mine area soil and water-conserving plant species, Caragana microphylla, Hippophae rhamnoides, and Artemisia ordosica, cyclic loading tests were conducted on taproots of the three plant species (1–5 mm diameter) via a TY8000 servo-type machine to investigate the taproots’ tensile properties response to repeated loading–unloading using simulated high wind pulling and runoff scouring. Our study revealed that the tensile force was positively correlated with the root diameter but the tensile strength was negatively correlated under monotonic and cyclic loading of the three plants’ taproots. However, after cyclic loading, the three plant species' taproots significantly enhanced the tensile force and strength more than monotonic loading (P

Abstract A lasting imbalance between fatty acid synthesis and consumption leads to non-alcoholic fatty liver disease (NAFLD), coupled with hepatitis and insulin resistance. Yet the details of the underlying mechanisms are not fully understood. Here, we unraveled that the expression of the transcription factor Zbtb18 is markedly decreased in the livers of both patients and murine models of NAFLD. Hepatic Zbtb18 knockout promoted NAFLD features like impaired energy expenditure and fatty acid oxidation (FAO), and induced insulin resistance. Conversely, hepatic Zbtb18 overexpression alleviated hepato-steatosis, insulin resistance, and hyperglycemia in mice fed on a high-fat diet (HFD) or in diabetic mice. Notably, in vitro and in vivo mechanistic studies revealed that Zbtb18 transcriptional activation of Farnesoid X receptor (FXR) mediated FAO and Clathrin Heavy Chain (CLTC) protein hinders NLRP3 inflammasome activity. This key mechanism by which hepatocyte’s Zbtb18 expression alleviates NAFLD and consequent liver fibrosis was further verified by FXR’s deletion and forced expression in mice and cultured mouse primary hepatocytes (MPHs). Moreover, CLTC deletion significantly abrogated the hepatic Zbtb18 overexpression-driven inhibition of NLRP3 inflammasome activity in macrophages. Altogether, Zbtb18 transcriptionally activates the FXR-mediated FAO and CLTC expression, which inhibits NLRP3 inflammasome’s activity alleviating inflammatory stress and insulin resistance, representing an attractive remedy for hepatic steatosis and fibrosis.

Abstract Non-dissociative chemisorption solid-state storage of hydrogen molecules in host materials is promising to achieve both high hydrogen capacity and uptake rate, but there is the lack of non-dissociative hydrogen storage theories that can guide the rational design of the materials. Herein, we establish generalized design principle to design such materials via the first-principles calculations, theoretical analysis and focused experimental verifications of a series of heteroatom-doped-graphene-supported Ca single-atom carbon nanomaterials as efficient non-dissociative solid-state hydrogen storage materials. An intrinsic descriptor has been proposed to correlate the inherent properties of dopants with the hydrogen storage capability of the carbon-based host materials. The generalized design principle and the intrinsic descriptor have the predictive ability to screen out the best dual-doped-graphene-supported Ca single-atom hydrogen storage materials. The dual-doped materials have much higher hydrogen storage capability than the sole-doped ones, and exceed the current best carbon-based hydrogen storage materials.

Abstract Single‐atom materials (SAMs) have become one of the most important power sources to push the field of energy conversion forward. Among the main types of energy, including thermal energy, electrical energy, solar energy, and biomass energy, SAMs have realized ultra‐high efficiency and show an appealing future in practical application. More than high activity, the uniform active sites also provide a convincible model for chemists to design and comprehend the mechanism behind the phenomenon. Therefore, we presented an insightful review of the application of the single‐atom material in the field of energy conversion. The challenges (e.g., accurate synthesis and practical application) and future directions (e.g., machine learning and efficient design) of the applications of SAMs in energy conversion are included, aiming to provide guidance for the research in the next step.

Abstract Background Most bone defects caused by bone disease or trauma are accompanied by infection, and there is a high risk of infection spread and defect expansion. Traditional clinical treatment plans often fail due to issues like antibiotic resistance and non-union of bones. Therefore, the treatment of infected bone defects requires a strategy that simultaneously achieves high antibacterial efficiency and promotes bone regeneration. Results In this study, an ultrasound responsive vanadium tetrasulfide-loaded MXene (VSM) Schottky junction is constructed for rapid methicillin-resistant staphylococcus aureus (MRSA) clearance and bone regeneration. Due to the peroxidase (POD)-like activity of VS4 and the abundant Schottky junctions, VSM has high electron–hole separation efficiency and a decreased band gap, exhibiting a strong chemodynamic and sonodynamic antibacterial efficiency of 94.03%. Under the stimulation of medical dose ultrasound, the steady release of vanadium element promotes the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). The in vivo application of VSM in infected tibial plateau bone defects of rats also has a great therapeutic effect, eliminating MRSA infection, then inhibiting inflammation and improving bone regeneration. Conclusion The present work successfully develops an ultrasound responsive VS4-based versatile sonosensitizer for robust effective antibacterial and osteogenic therapy of infected bone defects.

The fast and accurate series arc fault (SAF) identification method and its hardware implementation are the key to the development of arc fault circuit interrupter (AFCI) or arc fault detection device (AFDD). The SAF experiments under household multi-branch circuit conditions were conducted. And a novel SAF identification model based on lightweight one-dimensional (1-D) convolutional neural network was proposed. First, the main-circuit current signal was used as the input of the model. The 1-D convolutional layers and 1-D maximum pooling layers of the model were used to extract the features of the current signal. The fully connected neural network (FCNN) was used to identify whether or not there is a SAF in the circuit and determine the branch-circuit where the fault is located. Second, the second to fourth standard convolutional layers of the model were improved by using depthwise separable convolution, and the batch normalization layers were added to the model, so as to realize the optimal design of the model. Finally, the model was deployed to an embedded device and its performance was tested. When the sampling frequency is higher than 5 kHz, the accuracy of fault identification and fault line selection of the model in the embedded device is higher than 98.05% and 99.11%, respectively. The average runtime of single identification is 5.26 ms. It meets the technical requirements of household AFCI or AFDD.

Objective Conventional correction techniques were challenging and of high risk of neurological complications for the correction of severe and rigid kyphoscoliosis. A new technical note we developed and named as sequential correction, was used to treat severe and rigid kyphoscoliosis. The present study was to compare the clinical outcomes of sequential correction versus conventional correction for the treatment of severe and rigid kyphoscoliosis. Methods This is a respectively case–control study. Between January 2014 and December 2019, 36 adults underwent the surgical correction of severe and rigid kyphoscoliosis and were included in the present study. Among them, 20 adults underwent conventional correction, 16 adults underwent sequential correction. Major curve Cobb angle, kyphotic angle, coronal imbalance, and sagittal vertical axis were compared between two groups. The patient‐reported health‐related quality of life outcomes, including the Oswestry disability index score, and SRS‐22 questionnaire, were recorded. Independent samples t‐test, Mann–Whitney U test, and Wilcoxon signed‐rank test, were used to compare the differences between two groups according to the results of normal distribution test. Results In conventional correction group, the mean major curve Cobb angle was 122.50° preoperatively, 40.35° immediately after surgery, and 43.95° at final follow‐up postoperatively; the mean kyphotic angle was 97.45° preoperatively, 34.45° immediately after surgery, and 38.30° at final follow‐up postoperatively. In the sequential correction group, the mean major angle was 134.44° preoperatively, 44.56° immediately after surgery, and 46.25° at final follow‐up postoperatively; the mean kyphotic angle was 112.31° preoperatively, 39.00° immediately after surgery, and 40.38° at final follow‐up postoperatively. The mean major curve Cobb angle and kyphotic angle of both groups were improved significantly, while there were no significant differences between two groups (p > 0.001). Improved self‐reported quality of life scores were achieved postoperatively and at final follow‐up postoperatively, and there were no significant differences between the two groups. The total complication rate of the patients underwent conventional correction was 55%, and the total complication rate of the patients underwent sequential correction was 43.75%. The complication rate of the two groups showed no significant difference. Conclusions Sequential correction is an excellent and safe treatment for severe and rigid kyphoscoliosis in adults, with similar clinical outcomes with conventional correction. The total complication rate of the patients who underwent sequential correction was slightly lower than conventional correction.

AbstractSouthwestern China is a biodiversity hotspot due to its diverse topography and environment. Amorphophallus yunnanensis is a species of perennial herb that is mainly distributed throughout southwestern China. The genetic diversity and divergence in this species have not been assessed largely due to a lack of genomic resources. To help with the phylogeographic study, we sequenced and assembled the first complete chloroplast genome sequence of A. yunnanensis. The length of the chloroplast genome was 164,417 bp, with an average GC content of 36% (GenBank accession no. OR400247). The genome possessed a typical quadripartite structure, and the lengths of the large single-copy (LSC), small single-copy (SSC), and two inverted repeat (IR) regions were 92,149 bp, 15,182 bp, 28,543bp, and 28,543bp, respectively. A total of 128 genes were annotated across the genome, including 82 protein-coding genes, 8 rRNAs, and 38 tRNAs. The maximum likelihood (ML) phylogeny confirmed the phylogenetic position of Amorphophallus within Araceae, with the Amorphophallus species forming a single monophyletic clade with a high bootstrap value. The ML tree also indicated that A. yunnanensis was most closely related to A. coaetaneus. This newly sequenced chloroplast genome assembly will aid in future studies of genetic diversity, historical population dynamics, and geographic differentiation patterns of A. yunnanensis.

Abstract Background The incidence of Y chromosome microdeletions varies among men with infertility across regions and ethnicities worldwide. However, comprehensive epidemiological studies on Y chromosome microdeletions in Chinese men with infertility are lacking. We aimed to investigate Y chromosome microdeletions prevalence among Chinese men with infertility and its correlation with intracytoplasmic sperm injection (ICSI) outcomes. Methods This single-center retrospective study included 4,714 men with infertility who were evaluated at the Reproductive Center of the First Affiliated Hospital of Sun Yat-sen University between May 2017 and January 2021. Semen analysis and Y-chromosome microdeletion via multiplex polymerase chain reaction were conducted on the men. The study compared outcomes of 36 ICSI cycles from couples with male azoospermia factor (AZF)cd deletions with those of a control group, which included 72 ICSI cycles from couples without male Y chromosome microdeletions, during the same period. Both groups underwent ICSI treatment using ejaculated sperm. Results Among 4,714 Chinese men with infertility, 3.31% had Y chromosome microdeletions. The combined deletion of sY254 and sY255 in the AZFc region and sY152 in the AZFd region was the prevalent pattern of Y chromosome microdeletion, with 3.05% detection rate. The detection rates of AZF deletions in patients with normal total sperm count, mild oligozoospermia, severe oligozoospermia, cryptozoospermia, and azoospermia were 0.17%, 1.13%, 5.53%, 71.43%, and 7.54%, respectively. Compared with the control group, the AZFcd deletion group exhibited no significant difference in the laboratory results or pregnancy outcomes of ICSI cycles using ejaculated sperm. Conclusions This is the largest epidemiological study on Y chromosome microdeletions in Chinese men with infertility. The study results underline the necessity for detecting Y chromosome microdeletion in men with infertility and severe sperm count abnormalities, especially those with cryptozoospermia. The combined deletion of sY254 and sY255 in the AZFc region and sY152 in the AZFd region was the most prevalent Y chromosome microdeletion pattern. Among patients with AZFcd deletion and ejaculated sperm, ICSI treatment can result in pregnancy outcomes, similar to those without AZFcd deletion.

AbstractPlants in the genus Amorphophallus, many of which possess high konjac glucomannan content, are considered important cash crops in many Asian countries. Wild relatives of cultivated Amorphophallus species are valuable resources for the genetic improvement of these crops. To aid in future genetic research of wild germplasm resources of Amorphophallus, a single individual of Amorphophallus krausei Engler, Pflanzenr 1911 was collected from southwestern China, and its chloroplast genome was sequenced using next-generation sequencing technologies. The assembled chloroplast genome was 172,418 bp in length with a GC content of 35.23% (GenBank accession no. OR416863). A typical quadripartite structure was found in the genome, which was comprised of one large single-copy (LSC), one small single-copy (SSC), and two inverted repeats (IRs), with lengths of 91,983 bp, 15,591 bp, 32,422 bp, and 32,422 bp, respectively. A total of 132 genes were annotated in the genome, including 86 protein-coding genes, 38 tRNAs, and 8 rRNAs. A maximum likelihood (ML) tree of A. krausei and 17 other species in the family Araceae suggested that all Amorphophallus species formed a single monophyletic clade. A close relationship among A. konjac, A. albus, and A. krausei was also revealed by the phylogenetic tree. The newly sequenced chloroplast genome of A. krausei will support future genetic studies, particularly the assessment of genetic diversity, resource conservation, and phylogeographic research.

The ability to predict tourist movements has various practical applications, including recommendation, target marketing, and destination planning. Predictability determines the limit of the prediction accuracy of data and models and helps us understand the factors affecting the prediction accuracy. We first constructed a conceptual framework of factors influencing the predictability from three perspectives: tourist, destination, and space-time. In this study, we focused on factors affecting the tourist movement predictability using data collected from social media at the city level. We used two prediction models to understand the impact of the factors on predictability. We further analyzed the relationship between the factors and movement predictability. The results of this study demonstrate that the length of the tourist itinerary and the spatial scale of the study are key factors that influence model selection. In addition, the results indicate significant differences in the predictability of tourists with different tourism motivations.

When various urban functions are integrated into one location, they form a mixture of functions. The emerging big data promote an alternative way to identify mixed functions. However, current methods are largely unable to extract deep features in these data, resulting in low accuracy. In this study, we focused on recognizing mixed urban functions from the perspective of human activities, which are essential indicators of functional areas in a city. We proposed a framework to comprehensively extract deep features of human activities in big data, including activity dynamics, mobility interactions, and activity semantics, through representation learning methods. Then, integrating these features, we employed fuzzy clustering to identify the mixture of urban functions. We conducted a case study using taxi flow and social media data in Beijing, China, in which five urban functions and their correlations with land use were recognized. The mixture degree of urban functions in each location was revealed, which had a negative correlation with taxi trip distance. The results confirmed the advantages of our method in understanding mixed urban functions by employing various representation learning methods to comprehensively depict human activities. This study has important implications for urban planners in understanding urban systems and developing better strategies.

The high spatial complexities of soil temperature modeling over semiarid land have challenged the calibration–forecast framework, whose composited objective lacks comprehensive evaluation. Therefore, this study, based on the Noah land surface model and its full parameter table, utilizes two global searching algorithms and eight kinds of objectives with dimensional-varied metrics, combined with dense site soil moisture and temperature observations of central Tibet, to explore different metrics’ performances on the spatial heterogeneity and uncertainty of regional land surface parameters, calibration efficiency and effectiveness, and spatiotemporal complexities in surface forecasting. Results have shown that metrics’ diversity has shown greater influence on the calibration—predication framework than the global searching algorithm’s differences. The enhanced multi-objective metric (EMO) and the enhanced Kling–Gupta efficiency (EKGE) have their own advantages and disadvantages in simulations and parameters, respectively. In particular, the EMO composited with the four metrics of correlated coefficient, root mean square error, mean absolute error, and Nash–Sutcliffe efficiency has shown relatively balanced performance in surface soil temperature forecasting when compared to other metrics. In addition, the calibration–forecast framework that benefited from the EMO could greatly reduce the spatial complexities in surface soil modeling of semiarid land. In general, these findings could enhance the knowledge of metrics’ advantages in solving the complexities of the LSM’s parameters and simulations and promote the application of the calibration–forecast framework, thereby potentially improving regional surface forecasting over semiarid regions.

Abstract Background The presence of cancer cachexia is a significant adverse prognostic indicator in patients with malignant tumors. Cancer cachexia is a multifactorial syndrome characterized by a constant loss of skeletal muscles with or without a loss of weight, leading to immune dysfunction. We performed a retrospective study to investigate the influence of cachexia on the immunotherapy efficacy and prognosis for malignant tumors of the digestive system. Methods The present study adopts a cross‐sectional design. The prognosis data of patients with advanced cancer of the digestive system who received immunotherapy from September 2021 to December 2022 were analyzed. Cachexia was calculated using the change of the area of the psoas major muscle (PMMA) or the weight. We measured the change at the beginning of immunotherapy and at least 2 cycles afterward. The participants were categorized into the cachexia group and control group based on the evaluation criteria. Kaplan–Meier and Log‐rank methods were used for survival analysis. Cox proportional hazard model as a method to assess the contribution of different clinical factors to overall survival (OS) and progression‐free survival (PFS). Results A total number of 98 patients, including esophageal carcinoma (4, 4%), gastric (36, 37%), colorectal (51, 52%), and other cancer types (7, 7%), were enrolled. Fifty‐four patients were diagnosed with non‐cancer cachexia, and the cancer cachexia group included 44 patients. The median PFS in the cachexia group was shorter than that in the control group (130 days vs. 212 days). Their difference was not significant (p = .321). The survival rate of the patients without cachexia was longer than of those with cachexia (p = .027). The level of albumin and the number of metastatic organs were related to PFS (p = .020, p = .029). The albumin level was significantly associated with the OS of patients (p = .003). Conclusions The presence of cachexia was significantly associated with poor OS in patients with malignant tumors of the digestive system who received immunotherapy, not with PFS or the response to immunotherapy.

BackgroundIn addition to abnormal liver inflammation, the main symptoms of non-alcoholic steatohepatitis (NASH) are often accompanied by gastrointestinal digestive dysfunction, consistent with the concept of spleen deficiency (SD) in traditional Chinese medicine. As an important metabolic sensor, whether peroxisome proliferator-activated receptor alpha (PPARα) participates in regulating the occurrence and development of NASH with SD (NASH-SD) remains to be explored.MethodsClinical liver samples were collected for RNA-seq analysis. C57BL/6J mice induced by folium sennae (SE) were used as an SD model. qPCR analysis was conducted to evaluate the inflammation and metabolic levels of mice. PPARα knockout mice (PPARαko) were subjected to SE and methionine–choline-deficient (MCD) diet to establish the NASH-SD model. The phenotype of NASH and the inflammatory indicators were measured using histopathologic analysis and qPCR as well.ResultsThe abnormal expression of PPARα signaling, coupled with metabolism and inflammation, was found in the results of RNA-seq analysis from clinical samples. SD mice showed a more severe inflammatory response in the liver evidenced by the increases in macrophage biomarkers, inflammatory factors, and fibrotic indicators in the liver. qPCR results also showed differences in PPARα between SD mice and control mice. In PPARαko mice, further evidence was found that the lack of PPARα exacerbated the inflammatory response phenotype as well as the lipid metabolism disorder in NASH-SD mice.ConclusionThe abnormal NR signaling accelerated the vicious cycle between lipotoxicity and inflammatory response in NAFLD with SD. Our results provide new evidence for nuclear receptors as potential therapeutic targets for NAFLD with spleen deficiency.

Investigating mechanisms underlying genetic variation and differentiation of wild resources is critical for the utilization and improvement of crop germplasms. Amorphophallus species is an important economic crop in Southwest China for its glucomannan production. However, the wild populations of this genus are declining due to human activities. To investigate the genetic diversity and phylogenetic relationship of representative Amorphophallus species in Southwest China, the phylogenetic relationships between species were reconducted by using three chloroplast DNA (cpDNA) fragments and analyzing genetic diversity of six Amorphophallus species. The results were as follows: (1) The genetic diversity of wild Amorphophallus populations was generally low with an average haplotype diversity (Hd) of 0.428. In addition, nearly half of the total populations had only one haplotype. The haplotype diversity of each species varied from 0.704 to 0.983. (2) The genetic differentiation between each pair of six species was relatively high, and the genetic differentiation coefficient (FST) values ranged from 0.481 to 0.967. (3) The phylogenetic analysis suggested that 27 selected Amorphophallus species should be mainly divided into three clades Africa clade, Southeast Asia clade, and East Asian continent clade. A. paeoniifolius belonged to the Southeast Asia clade. The East Asian continent A clade included A. konjac and A. krausei, and East Asian continent B clade was comprised of A. kiusianus, A. yunnanensis and A. tonkinensis. Geographic isolation and human disturbance could have caused the low genetic diversity in wild populations of Amorphophallus. The divergence of the East Asian continent clade may be driven by the rapid radiation and ecological adaptation in species of this clade. These findings provide theoretical guidance for the conservation, sustainable utilization and breeding of Amorphophallus species in Southwest China.

Abstract Birth defect is a global threat to the public health systems. Mitigating neonatal anomalies is hampered by elusive molecular mechanisms of pathogenic mutations and poor subsequent translation into preventative measures. Applying appropriate strategies in China to promote reproductive health is particularly challenging, as the Chinese population compromises complex genomic diversity due to the inclusion of many ethnic groups with distinct genetic backgrounds. To investigate and evaluate the feasibility of implementing a pan-ethnic screening strategy, and guide future reproductive counselling, high-quality variants associated with autosome recessive (AR) diseases derived from the largest publicly available cohort of the Chinese population were re-analysed using a bottom-up approach. The analyses of gene carrier rates (GCRs) across distinct ethnic groups revealed that substantial heterogeneity existed potentially due to diverse evolutionary selection. The sampling population, sequencing coverage and underlying population structure contributed to the differential variants observed between ChinaMAP and the East Asian group in gnomAD. Beyond characteristics of GCR, potential druggable targets were additionally explored according to genomic features and functional roles of investigated genes, demonstrating that phase separation could be a therapeutic target for autosomal recessive diseases. A further examination of estimated GCR across ethnic groups indicated that most genes shared by at least two populations could be utilised to direct the design of a pan-ethnic screening application once sequencing and interpreting costs become negligible. To this end, a list of autosomal recessive disease genes is proposed based on the prioritised rank of GCR to formulate a tiered screening strategy.

The neuroinflammatory responses following ischemic stroke cause irreversible nerve cell death. Cell free-double strand DNA (dsDNA) segments from ischemic tissue debris are engulfed by microglia and sensed by their cyclic GMP-AMP synthase (cGAS), which triggers robust activation of the innate immune stimulator of interferon genes (STING) pathway and initiate the chronic inflammatory cascade. The decomposition of immunogenic dsDNA and inhibition of the innate immune STING are synergistic immunologic targets for ameliorating neuroinflammation. To combine the anti-inflammatory strategies of STING inhibition and dsDNA elimination, we constructed a DNase-mimetic artificial enzyme loaded with C-176. Nanoparticles are self-assembled by amphiphilic copolymers (P[CL35-b-(OEGMA20.7-co-NTAMA14.3)]), C-176, and Ce4+ which is coordinated with nitrilotriacetic acid (NTA) group to form corresponding catalytic structures. Our work developed a new nano-drug that balances the cGAS-STING axis to enhance the therapeutic impact of stroke by combining the DNase-memetic Ce4+ enzyme and STING inhibitor synergistically. In conclusion, it is a novel approach to modulating central nervus system (CNS) inflammatory signaling pathways and improving stroke prognosis.

Abstract Cognitive impairment is a core feature of schizophrenia, which is aggravated by antipsychotics-induced metabolic disturbance and lacks effective pharmacologic treatments in clinical practice. Our previous study demonstrated the efficiency of metformin in alleviating metabolic disturbance following antipsychotic administration. Here we report that metformin could ameliorate cognitive impairment and improve functional connectivity (FC) in prefrontal regions. This is an open-labeled, evaluator-blinded study. Clinically stable patients with schizophrenia were randomly assigned to receive antipsychotics plus metformin (N = 48) or antipsychotics alone (N = 24) for 24 weeks. The improvement in cognition was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Its association with metabolic measurements, and voxel-wise whole-brain FC with dorsolateral prefrontal cortex (DLPFC) subregions as seeds were evaluated. When compared to the antipsychotics alone group, the addition of metformin resulted in significantly greater improvements in the MCCB composite score, speed of processing, working memory, verbal learning, and visual learning. A significant time × group interaction effect of increased FC between DLPFC and the anterior cingulate cortex (ACC)/middle cingulate cortex (MCC), and between DLPFC subregions were observed after metformin treatment, which was positively correlated with MCCB cognitive performance. Furthermore, the FC between left DLPFC A9/46d to right ACC/MCC significantly mediated metformin-induced speed of processing improvement; the FC between left A46 to right ACC significantly mediated metformin-induced verbal learning improvement. Collectively, these findings demonstrate that metformin can improve cognitive impairments in schizophrenia patients and is partly related to the FC changes in the DLPFC. Trial Registration: The trial was registered with ClinicalTrials.gov (NCT03271866). The full trial protocol is provided in Supplementary Material.

Septic encephalopathy (SE) represents a severe inflammatory syndrome linked to elevated septic mortality rates, lacking specific therapeutic interventions, and often resulting in enduring neurological sequelae. The present investigation endeavors to elucidate the involvement of C-X-C Motif Chemokine Receptor 2 (CXCR2) in the pathogenesis of SE and to explore the potential of CXCR2 modulation as a therapeutic avenue for SE. Employing a murine SE model induced by lipopolysaccharide (LPS) administration, CXCR2 knockout mice and the CXCR2 inhibitor SB225002 were utilized to assess neutrophil recruitment, endothelial integrity, and transendothelial migration. Our findings substantiate that either CXCR2 deficiency or its inhibition curtails neutrophil recruitment without impacting their adhesion to cerebral endothelial cells. This phenomenon is contingent upon endothelial CXCR2 expression rather than CXCR2’s presence on neutrophils. Furthermore, the CXCR2 blockade preserves the integrity of tight junction protein ZO-1 and mitigates F-actin stress fiber formation in cerebral endothelial cells following septic challenge. Mechanistically, CXCL1-mediated CXCR2 activation triggers cerebral endothelial actin contraction via Rho signaling, thereby facilitating neutrophil transmigration in SE. These observations advocate for the potential therapeutic efficacy of CXCR2 inhibition in managing SE.

Next-generation communication systems demand the integration of sensing, communication, and power transfer (PT) capabilities, requiring high spectral efficiency, energy efficiency, and low cost while also necessitating robustness in high-speed scenarios. Integrated sensing and communication systems (ISACSs) exhibit the ability to simultaneously perform communication and sensing tasks using a single RF signal, while simultaneous wireless information and power transfer (SWIPT) systems can handle simultaneous information and energy transmission, and orthogonal time frequency space (OTFS) signals are adept at handling high Doppler scenarios. Combining the advantages of these three technologies, a novel cyclic prefix (CP) OTFS-based integrated simultaneous wireless sensing, communication, and power transfer system (ISWSCPTS) framework is proposed in this work. Within the ISWSCPTS, the CP-OTFS matched filter (MF)-based target detection and parameter estimation (MF-TDaPE) algorithm is proposed to endow the system with sensing capabilities. To enhance the system’s sensing capability, a waveform design algorithm based on CP-OTFS ambiguity function shaping (AFS) is proposed, which is solved by an iterative method. Furthermore, to maximize the system’s sensing performance under communication and PT quality of service (QoS) constraints, a semidefinite relaxation (SDR) beamforming design (SDR-BD) algorithm is proposed, which is solved using through the SDR technique. The simulation results demonstrate that the ISWSCPTS exhibits stronger parameter estimation performance in high-speed scenarios compared to orthogonal frequency division multiplexing (OFDM), the waveform designed by CP-OTFS AFS demonstrates superior interference resilience, and the beamforming designed by SDR-BD strikes a balance in the overall performance of the ISWSCPTS.

IP network expansion is a common maintenance method for communication operators to keep the network running smoothly.The core is to predict the network traffic trend in the future period.IP network traffic is very complex, with local uncertainty, burstiness, heterogeneity, etc., which brings difficulties to prediction.A prediction method for complex network traffic was proposed.It adopted an encode-decode structure, adding global features to the encoding layer, and combining global features and local features in the decoding layer to solve local uncertainties.The model used sample balance, normalization and other methods to extract the commonality of the data as much as possible to avoid the heterogeneity of the data.And emergencies were alleviated by increasing prior knowledge.The overall model had fewer parameters and had strong generalization performance, at the same time, the combination of artificial features and automatic features ensured the accuracy of the shallow network.The experimental results show that the proposed method has the characteristics of high accuracy and strong generalization performance.At present, this method has been applied on a large scale in engineering.

Abstract Objective The present study is to evaluate the clinical outcomes of the sequential correction of severe and rigid kyphoscoliosis. Methods Between January 2014 and December 2020, 27 adults with severe and rigid kyphoscoliosis underwent sequential correction combined with posterior grade 4 or grade 5 spinal osteotomy. Radiological parameters, including the major curve Cobb angle, kyphotic angle, coronal imbalance, and sagittal vertical axis (SVA), were compared. Patient self-reported health-related quality of life (HRQOL) scores were used to evaluate clinical outcomes. Results The mean major curve Cobb angle improved from 134.30 ± 13.24° to 44.48 ± 9.34° immediately after surgery and to 46.11 ± 8.94° at the final follow-up. The mean kyphotic angle improved from 112.15 ± 20.28° to 38.63 ± 15.00° immediately after surgery and to 39.85 ± 14.92° at the final follow-up. The mean preoperative major curve Cobb angle of grade 5 spinal osteotomy group was higher than that of grade 4 spinal osteotomy group. Coronal imbalance and SVA slightly improved. The patient self-reported HRQOL scores improved postoperatively and at the final follow-up. Activity, appearance and total scores of the SRS-22 of the grade 5 spinal osteotomy group at the final follow-up were significantly better than those of the grade 4 spinal osteotomy group. Conclusions Sequential correction combined with posterior grade 4 or grade 5 spinal osteotomies is an excellent and safe treatment for severe and rigid kyphoscoliosis in adults. Sequential correction combined with posterior grade 5 spinal osteotomies can be used to correct severe and rigid kyphoscoliosis with higher major curve Cobb angle.

Abstract Background Microglia play a pivotal role in neuroinflammation, while obesity triggers hypothalamic microglia activation and inflammation. Sirt6 is an important regulator of energy metabolism in many peripheral tissues and hypothalamic anorexic neurons. However, the exact mechanism for microglia Sirt6 in controlling high-fat diet-induced obesity remain unknown. Methods Microglia Sirt6 expression levels under various nutritional conditions were measured in the hypothalamus of mice. Also, microglia Sirt6-deficient mice were provided various diets to monitor metabolic changes and hypothalamic inflammatory response. Besides, RNA-seq and Co-IP of microglia with Sirt6 alterations were conducted to further investigate the detailed mechanism by which Sirt6 modulated microglia activity. Results We found that Sirt6 was downregulated in hypothalamic microglia in mice given a high-fat diet (HFD). Additionally, knockout of microglia Sirt6 exacerbated high-fat diet-induced hypothalamic microglial activation and inflammation. As a result, mice were more prone to obesity, exhibiting a decrease in energy expenditure, impaired glucose tolerance, insulin and leptin resistance, and increased food intake. In vitro, Sirt6 overexpression in BV2 cells displayed protective effects against oleic acid and palmitic acid treatment-derived inflammatory response. Mechanically, Sirt6 deacetylated and stabilised NRF2 to increase the expression of anti-oxidative genes and defend against reactive oxygen species overload. Pharmacological inhibition of NRF2 eliminated the beneficial modulating effects of Sirt6 on microglial activity. Conclusion Collectively, our results revealed that microglial Sirt6 was a primary contributor of microglial activation in the central regulation of obesity. Thus, microglial Sirt6 may be an important therapeutic target for obesity.

Amorphophallus coaetaneus S. Y. Liu & S. J. Wei 1986 is a perennial herb belonging to the Araceae family in southwestern China (Guangxi and Yunnan provinces). Although this species have not been list in the red list of International Union for Conservation of Nature (IUCN), the populations are declining due to human over exploitation. To help to genetic diversity studies, we sequenced and assembled the complete chloroplast (cp) genome of A. coaetaneus (GenBank accession number of national center for biotechnology information (NCBI): OQ404947). The assembled genome revealed 175,465 bp in length with a GC content of 34.90%, including a large single-copy (LSC) region (98,561 bp), a small single-copy (SSC) region (16,504 bp) and two inverted repeat regions (IRs) (30,200 bp each). A total of 133 genes were annotated, of which 85 are protein-coding genes, 40 are tRNA genes and 8 are rRNA genes. As an output of this study, a maximum likelihood (ML) phylogenetic inference of 16 Araceae species clustered all four Amorphophallus species in one clade, and showed a relatively close relationship between the tribes Pythonieae and Colocasieae. The cp genome will serve as a basis in a more extensive molecular works covering all possible extant population of Amorphophallus, as well as conservation, breeding, and other ethnobotanical utilization of this species.