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Sampling density and depth play crucial roles in three-dimensional (3D) soil modeling and prediction, particularly in digital soil mapping (DSM). However, previous studies have yielded inconsistent and even contradictory results regarding impacts of sampling density and depth on the accuracy of 3D DSM. Hence, this study aimed to evaluate the impacts of sampling depth, vertical sampling density and lateral profile density on 3D soil mapping accuracy based on a case study of soil organic carbon (SOC). To achieve this, a comprehensive analysis was conducted based on 511 soil samples collected from 111 profiles in a local hilly area spanning 5.52 km2 in China. A 3D regression geostatistical approach was employed for the analysis. The results revealed that samples taken from different depth intervals exhibited varying degrees of importance in relation to prediction accuracy. Notably, a reduced number of surface soil samples (0–0.3 m) led to significant fluctuations in the accuracy of predictions for the entire soil profile. Furthermore, a lower number of subsurface soil samples (0.3–0.6 m) also diminished the overall prediction accuracy, while the influence of deeper soil samples (0.6–1.2 m) on the overall accuracy was relatively less pronounced. Reducing the number of profiles for calibration led to significantly worse and more variable prediction accuracy, compared to reducing vertical samples. For 3D mapping, this study recommends prioritizing the collection of additional lateral profiles, specifically focusing on surface and subsurface soils, especially for properties that display vertical variation similar to SOC.

Bispecific T-cell-engaging antibodies are a growing class of therapeutics with numerous molecules being tested in clinical trials and, currently, seven of them have received market approval. They are structurally complex and function as adaptors to redirect the cytotoxicity of T cells to kill tumor cells. T-cell-engaging bispecific antibodies can be generally divided into two categories: IgG/IgG-like and non-IgG-like formats. Different formats may have different intrinsic potencies and physiochemical properties, and comprehensive studies are needed to gain a better understanding of how the differences in formats impact on structural and functional characteristics. In this study, we designed and generated bispecific T-cell-engaging antibodies with IgG-like (DVD-Ig) and non-IgG (BiTE) formats. Both target the same pair of antigens (EGFR and CD3) to minimize the possible influence of targets on functional characterization. We performed a side-by-side comparison to assess differences in the physiochemical and biological properties of these two bispecific T-cell-engaging antibodies using a variety of breast and ovarian cancer cell-based functional assays to delineate the structural–functional relationships and anti-tumor activities/potency. We found that the Fc portion of T-cell-engaging bispecific antibodies can significantly impact antigen binding activity, potency, and stability in addition to eliciting different mechanisms of action that contribute the killing of cancer cells.

Neurodegeneration with brain iron accumulation (NBIA) is a clinically and genetically heterogeneous disease characterized by increased iron deposition in the basal ganglia and progressive degeneration of the nervous system in adulthood. However, in early childhood, there were no characteristic features to perform early diagnosis. In our study, a female child exhibited global developmental delay, intellectual disability, and febrile seizure without other distinct clinical phenotypes. Through whole exome sequencing (WES), a de novo nonsense mutation (c.726C > G, p. Tyr242Ter) of WDR45 gene was identified in this child. She was finally diagnosed as β‐propeller protein-associated neurodegeneration (BPAN), one of the recently identified subtypes of NBIA. This mutation could act as a premature stop codon (PSC) which rendered the mutated transcripts to be degraded by nonsense-mediated mRNA decay (NMD), leading to decreased levels of PSC-containing mRNAs. Additionally, through mini-gene splicing assays, this mutation could result in an unprecedented novel transcript with the exon 9 of WDR45 excluded by nonsense-associated splicing alteration (NASA). Transcriptome sequencing (RNA-seq) on total RNAs from PBMCs of the trio revealed three types of alternative splicing events in the patient. Further research implied that downregulation of iron transport genes (TFRC, TFR2, SCARA5) might be the underlying mechanism for the iron accumulation in patients with deficient WDR45. This is the first report about NASA happening in WDR45. It implies that nonsense mutations approximal to splicing sites could affect the disease pathogenesis through more than one molecular mechanism and should be taken into consideration when conducting genetic counseling.

Gypenosides (Gyp) are bioactive components of Gynostemma pentaphyllum that have a variety of pharmacological properties. Extracts of G. pentaphyllum have been found to be effective in the reduction of blood sugar and lipids and prevention of atherosclerosis. Here, the functions of Gyp and the mechanisms underlying their effects on atherosclerosis were investigated. Mice were allocated to three groups, namely, the control (C57BL/6), atherosclerosis model (ApoE−/− mice with high-fat diet), and Gyp-treated groups. Differentially expressed mRNAs, miRNAs, circRNA, and differential metabolites among the groups were analyzed. The results showed that “Fatty acid metabolism”, “Fatty acid elongation”, “Cytokine-cytokine receptor interaction”, and “PI3K-Akt signaling pathway”, amongst others, were involved in treatment process. Differentially expressed genes, including Fabp1, Apoe, FADS1, ADH1, SYNPO2, and Lmod1were also identified. Mmu-miR-30a and mmu-miR-30e showed reduced expression in atherosclerosis models but were increased following Gyp treatment, suggesting involvement in the effects of Gyp. In addition, chr5:150604177-150608440 were found to interact with mmu-miR-30a and mmu-miR-30e to regulate their abundance. In terms of metabolomics, Gyp may regulate biological processes involving PGD2 and PGJ2, potentially alleviating atherosclerosis. In conclusion, Gyp appeared to have complex effects on atherosclerosis, most of which were positive. These results support the use of Gyp in the treatment of atherosclerosis.

Increasing demands for livestock products have stimulated rapid increases in the number of livestock and the scale of farming, thus increasing pressure on resources and the environment. Coordinating the development of livestock production (LP) with residential consumption (RC), resources and the environmental carrying capacity (RECC) is important to ensure sustainable development. In this study, the entropy weight method and the improved-coupling coordination degree (CCD) model were used to identify the spatial–temporal coordination development characteristics of livestock production-residential consumption-resource and environmental carrying capacity (LRRE). Furthermore, the spatial autocorrelation model (SAM) and gray model (GM) were used to analyze the spatial aggregation characteristics and future development trends of the CCDs of the LRRE in China. The findings show that the CCDs of the LRRE values in 31 Chinese provinces increased from 2005 to 2020, but no provinces reached a high coordination level. Specifically, the coordinated development level of LRRE is relatively high in the central, eastern and northeastern regions and relatively low in the western region. The spatial autocorrelation analysis confirmed that the high-high (H-H) aggregation areas were mainly distributed in the northeastern, eastern, and central regions, while low-high (L-H) agglomeration was distributed in the western region. This phenomenon is mainly attributed to the continuous expansion of the scale of livestock production in western China. Regions with relatively developed economies have more funds to invest in environmental protection projects. Using GM method, we find that the CCDs of LRRE in 31 provinces in China will increase from 2021 to 2030, and all provinces will reach the basic coordination level. However, most of the western regions will barely reach the basic coordination level. This result indicates that the low level of LRRE development in western China may be difficult to change in the short term. The level of coordinated LRRE development in the relatively developed eastern region is increasing. The spatial layout of China’s livestock industry should be appropriately adjusted, its expansion rate in the western region should be decreased, and the ecological environment of the areas bordering the western and central regions should be improved. These findings have practical implications for other large livestock production countries. Promoting the coordinated development of LRRE is also an important condition for agricultural transformation in developing countries, especially for improving the environment in key areas of the livestock industry.

Abstract Recent findings have shown that the level of interleukin‐35 (IL‐35) is abnormal in several autoimmune diseases. Nonetheless, whether IL‐35 participates in the pathogenesis of immune thrombocytopenia (ITP) remains unclear. The current study investigates whether IL‐35 modulates megakaryopoiesis. The results show that IL‐35 receptors are progressively expressed on bone marrow megakaryocytes during the in vitro differentiation of CD34+ progenitors. IL‐35 increases the number of megakaryocyte colony‐forming units through the Akt pathway. The level of bone marrow IL‐35 is reduced in ITP patients, and the decreased level of IL‐35 may inhibit megakaryopoiesis. Then, the potential causes of decreased IL‐35 in ITP patients are explored. The primary type of cell that secretes IL‐35, known as IL‐35‐producing regulatory T cells (iTr35), is reduced in ITP patients. Bone marrow mesenchymal stem cells (MSCs) from ITP patients exhibit an impaired capability of inducing iTr35 due to enhanced apoptosis, which may contribute to the reduced level of bone marrow IL‐35 in ITP patients. Iguratimod promotes megakaryocyte development and differentiation by elevating the expression of IL‐35 receptors on megakaryocytes. Iguratimod improves response rates and reduces bleeding symptoms in corticosteroid‐resistant ITP patients.

Objective To investigate the correlations between multigene alterations and clinicopathological features in papillary thyroid carcinoma (PTC) samples. Methods In this retrospective study, 111 cytological specimens of thyroid nodules, including 74 PTC samples and 37 benign samples, were analyzed using a 22-gene mutation assay employing next-generation sequencing. Clinicopathological information was retrospectively collected and analyzed. Results Gene alterations were associated with a higher rate of lymph node metastasis (LNM) and thyroid capsular invasion, a lower rate of coexisting Hashimoto's thyroiditis, the classical PTC subtype, and younger age (

Purpose: Postoperative pain is prevalent and severe complication in elderly surgical patients. Multiple studies propose that a small dose of esketamine administered intraoperatively can alleviate postoperative pain and curtail opioid usage. We aimed to evaluate the impact of esketamine on postoperative acute pain among elderly patients with gastrointestinal tumors. Patients and methods: This is a prospective, parallel-group, randomized controlled trial. Ninety patients aged 60 and above, undergoing resection of gastrointestinal tumors, were randomly assigned to two groups: esketamine group (Group S, a single dose of 0.25 mg/kg and 0.1 mg/kg/h infusion) and control group (Group C, saline). Visual Analogue Scale (VAS) pain scores were the primary outcome. Remifentanil consumption, instances of rescue analgesia, delirium, sleep quality, postoperative recovery quality, serum levels of inflammatory cytokines, and adverse events within 72 h post-surgery were secondary outcomes, respectively. Results: Data of 87 of 99 eligible patients were analyzed. VAS scores at rest in Group S were lower than those in Group C at 6 h [1.2 (0.6, 1.6) vs 1.6 (1.0, 2.0), P = 0.003], 12 h [1.4 (1.0, 2.0) vs 2.0 (1.5, 2.0), P

Auricularia delicata (Mont.) Henn. 1893 is an edible and medicinal jelly mushroom popular in China. Here, we report the assembly and annotation of a complete A. delicata mitochondrial genome based on data sequenced using an Illumina NovaSeq 6000 platform. The length of the complete circular A. delicata mitochondrial genome is 189,696 bp, with a GC content of 34.1%. The A. delicata mitochondrial genome contains 60 genes, including 32 protein-coding genes, 26 tRNA genes, and two rRNA genes. Phylogenetic analysis indicated that A. delicata clustered with the Auricularia group, alongside A. auricula-judae and A. heimuer. Additionally, A. delicata was found to be genetically distant from other species of Polyporales, Russulales, and Agaricales. This genome will provide an invaluable reference for the continued study and utilization of A. delicata and other Auricularia species.

Abstract Background High-fat diet (HFD) is closely associated with the increased prevalence of inflammatory bowel disease (IBD). Excessive gut microbial metabolite deoxycholic acid (DCA) caused by HFD plays significant roles in eliciting intestinal inflammation, however, the mechanism underlining the induction of inflammatory response by DCA has not been fully elucidated. The purpose of this study was to investigate the role of DCA in the triggering of inflammation via affecting CD4+ T cell differentiation. Results Murine CD4+T cells were cultured under Th1, Th2 or Th17-polarizing conditions treated with or without different dosage of DCA, and flowcytometry was conducted to detect the effect of DCA on CD4+ T cell differentiation. Alteration of gene expression in CD4+ T cells upon DCA treatment was determined by RNA-sequencing and qRT-PCR. Bioinformatic analysis, cholesterol metabolic profiling, ChIP assay and immuno-fluorescent staining were further applied to explore the DCA-regulated pathway that involved in CD4+T cell differentiation. The results showed that DCA could dose-dependently promote the differentiation of CD4+ T cell into Th17 linage with pathogenic signature. Mechanistically, DCA stimulated the expression of cholesterol biosynthetic enzymes CYP51 and led to the increased generation of endogenous RORγt agonists, including zymosterol and desmosterol, therefore facilitating Th17 differentiation. Up-regulation of CYP51 by DCA was largely mediated via targeting transcription factor SREBP2 and at least partially through bile acid receptor TGR5. In addition, DCA-supplemented diet significantly increased intestinal Th17 cell infiltration and exacerbated TNBS-induced colitis. Administration of cholestyramine to eliminate fecal bile acid obviously alleviated colonic inflammation accompanied by decreased Th17 cells in HFD-fed mice. Conclusions Our data establish a link between DCA-induced cholesterol biosynthesis in immune cells and gut inflammation. Modulation of bile acid level or targeting cholesterol metabolic pathway may be potential therapeutic measurements for HFD-related colitis.

Abstract Background Spinal cord injury (SCI), which causes loss of sensory and motor function in the body below the level of injury, is a devastating disease of the central nervous system. SCI leads to severe secondary immunosuppression, called SCI-induced immunodeficiency syndrome (SCI-IDS), which is characterized by increased susceptibility to infection and further exacerbates neurological dysfunction. Several studies have suggested that SCI-IDS is an independent risk factor for poor neurological prognosis. SCI-IDS predominantly occurs following injury above the T5 levels and eventually leads to systemic immune failure, possibly via the sympathetic–adrenal medullary axis and the hypothalamic‒pituitary‒adrenal (HPA) axis. However, the mechanism remains unclear. Methods and objectives The concentrations of adrenocorticotropic hormone and cortisol in plasma, as well as changes in sympathetic activity (blood pressure and catecholamine levels in plasma), were assessed in rats in the high-level (T3) spinal cord injury (T3-SCI) group and the low-level (T10) spinal cord injury (T10-SCI) group. Second, the differential regulation of the gene network between the sympathetic–adrenal medullary axis and the HPA axis was explored by histology and multitissue transcriptomics, and the neuroendocrine–immune network associated with SCI-IDS was further elucidated. Results The spleen and thymus gland, which are secondary immune organs, were significantly atrophied in rats in the T3-SCI group, and the white pulp of the spleen was significantly atrophied. The level of cortisol, which is mediated by the adrenal glands, was markedly elevated, but norepinephrine levels were markedly decreased. There was no difference in adrenocorticotropic hormone expression between any of the groups. The transcriptome analysis results showed that the downregulated differentially expressed genes (DEGs) in the T3-SCI group were enriched in the GO term immunoregulation, indicating that splenic immune function was markedly impaired after high-level SCI. The upregulated DEGs in the hypothalamus (hub genes: Nod2, Serpine1, Cebpb, Nfkbil1, Ripk2, Zfp36, Traf6, Akap8, Gfer, Cxcl10, Tnfaip3, Icam1, Fcgr2b, Ager, Dusp10, and Mapkapk2) were significantly enriched in inflammatory pathways, and the downregulated genes (hub genes: Grm4, Nmu, P2ry12, rt1-bb1, Oprm1, Zfhx2, Gpr83, and Chrm2) were enriched in pathways related to inhibitory Gi-mediated G protein-coupled receptor (Gi-GPCR) neurons and neuropeptide changes. The upregulated genes in the adrenal glands (hub genes: Ciart, per2, per3, cry1, and cry2) were enriched in cortisol secretion and circadian rhythm changes, and the downregulated genes (hub genes: IL7r, rt1-bb, rt1-bb1, rt1-da, rt1-ba, cd74, cxcr3, vcam1, ccl5, bin1, and IL8) were significantly enriched in MHC-mediated immune responses. Conclusions To explore the possible mechanism underlying SCI-IDS, this study assessed the differential regulation of the gene network associated with neuroendocrine immunity after SCI. Progressive neuroinflammation spreads after injury, and neurotransmission through Gi-mediated G protein-coupled receptors in the HPA axis and neuropeptide production by the hypothalamus are inhibited. Disruption of the connection between the hypothalamus and the adrenal glands causes autonomous regulation of the adrenal glands, disturbance of circadian rhythm and finally hypercortisolemia, leading to general suppression of peripheral adaptive immunity. Neuraxial nerve inflammation caused by SCI persists indefinitely, blocking nerve repair; persistent system-wide immunosuppression in the periphery results in increased susceptibility to infection, leading to poor neurological prognosis.

An increasing number of novel biomaterials have been applied in wound healing therapy. Creating beneficial environments and containing various bioactive molecules, hydrogel- and extracellular vesicle (EV)-based therapies have respectively emerged as effective approaches for wound healing. Moreover, the synergistic combination of these two components demonstrates more favorable outcomes in both chronic and acute wound healing. This review provides a comprehensive discussion and summary of the combined application of EVs and hydrogels to address the intricate scenario of wounds. The wound healing process and related biological mechanisms are outlined in the first section. Subsequently, the utilization of EV-loaded hydrogels during the wound healing process is evaluated and discussed. The moist environment created by hydrogels is conducive to wound tissue regeneration. Additionally, the continuous and controlled release of EVs from various origins could be achieved by hydrogel encapsulation. Finally, recent in vitro and in vivo studies reported on hydrogel dressings loaded with EVs are summarized and challenges and opportunities for the future clinical application of this therapeutic approach are outlined.

A foundation pit is constructed in the floodplain of Yangtze River, and a deep and thick layer of large-particle pebble gravel exists below the base slab, thus forming a connected supply channel with the adjacent Yangtze River. The large water volume, high water pressure, and strong permeability of this layer bring great risks to the foundation pit construction. In view of the fact that conventional waterproof curtain construction technologies such as the deep mixing column and high-pressure jet grouting column cannot meet the engineering requirements under these kinds of geological and environmental conditions, a new waterproof curtain construction technology that combines the trenching technology of the diaphragm wall with the TRD (Trench cutting Remixing Deep wall) technology is proposed, i.e., the trenching-and-replacing-style TRD technology, as well as the construction process of this technology, is presented. After the waterproof curtain is built using the proposed technology, the strength, integrity, uniformity, and service performance of the waterproof curtain wall are tested and evaluated by the comprehensive methods of coring, borehole television imaging, resistivity CT, and a group well pumping test. The results show that the proposed technology overcomes the adverse effects of underlying large-particle pebble gravel layer, and the waterproof curtain built by it effectively cuts off the hydraulic connection inside and outside the pit. The technical proposal can provide useful references for similar projects.

This paper proposes a prescribed performance control policy for spacecraft attitude tracking control. The designed controller employs a kind of performance envelope function that can configure the convergence rate arbitrarily. Moreover, the controller design is based on the barrier Lyapunov function and indirect adaptive methods, which can suppress the fluctuation of external disturbances to obtain lower steady-state errors. Compared to prior studies on spacecraft attitude tracking, the proposed policy can arbitrarily configure the system convergence performance to achieve performance trade-offs in different scenarios. Moreover, the barrier Lyapunov function design and adaptive methods can achieve low steady-state errors with low computational resource consumption. Simulations that verify its effectiveness and superiority are provided herein.

The mechanisms of mAb-induced ADCC have been well established. However, the ADCC bioassays used to quantify mAb-induced ADCC require continued development/refinement to properly assess and compare the potency of newly developed therapeutic mAbs and biosimilars to meet regulatory requirements. We used trastuzumab and a lactate dehydrogenase (LDH)-based ADCC bioassay as a model to define critical parameters of the ADCC bioassay, describing how several bioassay parameters, including preparation of effector cells, E/T ratio, target cell selection, bioassay media components, and treatment time can influence the data quality of the ADCC activity. We confirm that a 4 to 24 h recovery cultivation is required to restore peripheral blood mononuclear cells (PBMCs) and natural killer (NK) cell activity toward ADCC when using cryopreserved PBMCs. Furthermore, we delineated the cellular mechanisms underlying the restored ADCC activity following the recovery cultivation. We observed that CD69, an early marker of NK cell activation, was upregulated and a new subset CD56dim/CD16dim population was dramatically increased in the recovered NK cells, which led to an increase in expression and secretion of perforin, granzyme B, and cytokine production. This study provides comprehensive technical insights into ADCC bioassay optimization to inform trastuzumab biosimilar development. The knowledge gained from this study can also be leveraged to guide bioassay development for therapeutic mAbs with ADCC as the primary mechanism of action.

ABSTRACTThe purpose of this study is to establish a clinical prediction model to discriminate patients at high risk of Klebsiella pneumoniae (KP) colonization before allogeneic hematopoietic stem cell transplantation (allo-HSCT) and evaluate the impact of KP colonization on clinical outcomes after allo-HSCT. We retrospectively collected data from 2,157 consecutive patients receiving allo-HSCT between January 2018 and March 2022. KP colonization was defined as a positive test for KP from a pharyngeal or anal swab before allo-HSCT. Logistic regression was used to build a clinical prediction model. Cox regression analyses were performed to explore the effect of KP colonization on clinical outcomes. Among all the inpatients, 166 patients had KP colonization and 581 with no positive pathogenic finding before transplantation. Seven candidate predictors were entered into the final prediction model. The prediction model had an area under the curve of 0.775 (95% CI 0.723–0.828) in the derivation cohort and 0.846 (95% CI: 0.790–0.902) in the validation cohort. Statistically significantly different incidence rates were observed among patient groups with clinically predicted low, medium, and high risk for KP infection (P < 0.001). The presence of KP colonization delayed platelet engraftment (P < 0.001) and patients with KP colonization were more likely to develop KP bloodstream infections within 100 days after allo-HSCT (P < 0.0001). Patients with KP colonization had higher non-relapse mortality (P = 0.032), worse progression-free survival (P = 0.0027), and worse overall survival within 100 days after allo-HSCT (P = 0.013). Our findings suggest that increased awareness of risks associated with pre-transplantation bacterial colonization is warranted.IMPORTANCESeveral studies have identified that Klebsiella pneumoniae (KP) is among the most common and deadly pathogens for patients in hospital intensive care units and those receiving transplantation. However, there are currently no studies that evaluate the impact of KP colonization to patients undergoing allogeneic hematopoietic stem cell transplantation. Our results confirm that pre-existing KP colonization is relatively common in a hematology transplant ward setting and negatively affects post-transplantation prognosis. Our clinical prediction model for KP colonization can support early intervention in patients at high risk to avoid subsequent bloodstream infections and improve survival outcomes. Altogether, our data suggest that increased awareness of risks associated with pre-transplantation bacterial colonization is warranted. Future studies are needed to confirm these findings and to test early intervention strategies for patients at risk of complications from KP infection.

Three-dimensional (3D) phenotyping is important for studying plant structure and function. Light detection and ranging (LiDAR) has gained prominence in 3D plant phenotyping due to its ability to collect 3D point clouds. However, organ-level branch detection remains challenging due to small targets, sparse points, and low signal-to-noise ratios. In addition, extracting biologically relevant angle traits is difficult. In this study, we developed a stratified, clustered, and growing-based algorithm (SCAG) for soybean branch detection and branch angle calculation from LiDAR data, which is heuristic, open-source, and expandable. SCAG achieved high branch detection accuracy (F-score = 0.77) and branch angle calculation accuracy (r = 0.84) when evaluated on 152 diverse soybean varieties. Meanwhile, the SCAG outperformed 2 other classic algorithms, the support vector machine (F-score = 0.53) and density-based methods (F-score = 0.55). Moreover, after applying the SCAG to 405 soybean varieties over 2 consecutive years, we quantified various 3D traits, including canopy width, height, stem length, and average angle. After data filtering, we identified novel heritable and repeatable traits for evaluating soybean density tolerance potential, such as the ratio of average angle to height and the ratio of average angle to stem length, which showed greater potential than the well-known ratio of canopy width to height trait. Our work demonstrates remarkable advances in 3D phenotyping and plant architecture screening. The algorithm can be applied to other crops, such as maize and tomato. Our dataset, scripts, and software are public, which can further benefit the plant science community by enhancing plant architecture characterization and ideal variety selection.

Tropical forests are widely regarded as the Earth’s most important ecosystems, yet they are severely threatened by anthropogenic disturbances. Rapid and extensive monitoring of forest structure and biodiversity is crucial for developing ecologically sound conservation and restoration strategies. Airborne light detection and ranging (LiDAR) can effectively monitor three-dimensional forest canopy structures. Traditionally, LiDAR-based plant diversity estimation has relied on individual tree-based and area-based approaches. However, these approaches face significant challenges in tropical forests due to their complex canopy structures and diverse plant compositions. Therefore, by proposing a novel community-based approach, this study aims to examine the relationship between field-derived biodiversity indices and LiDAR-derived canopy structural metrics of plant communities in a species-rich ForestGEO forest dynamic plot in tropical Hong Kong. Our goal is to determine whether canopy structural metrics extracted from airborne LiDAR data can serve as a robust and efficient alternative for expediting plant diversity monitoring in highly dense and diverse tropical forests. Our results indicate that an integration watershed segmentation technique (for automatic patch-scale plant community delineation), LiDAR-derived canopy structural metrics, and machine learning-based random forest regression analysis can provide accurate predictions of community-based species diversity indices. Among various diversity indices, species richness and the Shannon-Wiener index are most accurately estimated using LiDAR-derived metrics. This study reveals that species richness is predominantly influenced by the existence of multi-layered canopy structures, whereas the Shannon-Wiener index is associated with both multi-layered structures and canopy morphologies. Overall, our findings showcase the immense potential of airborne LiDAR data in advancing the monitoring of structure and biodiversity in dense-canopy and species-rich tropical forests in a spatially explicit manner.

Objectives: This study aimed to investigate the prevalence and influencing factors of medication adherence in children with central precocious puberty (CPP), and provide references for clinical practice.Methods: Children under 12 years of age with CPP and their caregivers at a women’s and children’s hospital were selected for a cross-sectional study from February to May 2023, and a questionnaire was used to collect basic characteristics of pediatric patients and their caregivers, information of medication, cognition of medication, and medication adherence. The 8-item Morisky Medication Adherence Scale (MMAS-8) was adopted to assess medication adherence, and the potential influencing factors were explored by univariate and multivariate analyses.Results: A total of 125 valid questionnaires were collected. The medication adherence rate of children with CPP reported by caregivers was 76.0%. The univariate analysis showed that the percentage of parental caregivers (p = 0.027), the age of caregivers (p = 0.029), the education level of caregivers (p = 0.001), the financial burden (p < 0.000), the incidence of adverse effects (p = 0.008), and the cognition of medication including the importance of medication (p = 0.002), the dosage of medication (p = 0.002), the adverse effects of medication (p = 0.007), the harm of non-compliance with medication (p < 0.000), and the evaluation of the price of medication (p = 0.003) in the poor adherence group were significantly inferior to those in the better adherence group. The multivariate analysis showed that the higher incidence of adverse effects (p = 0.20), not understanding the harm of non-compliance with medication (p = 0.004), and evaluation of the price of medication as expensive (p = 0.043) were independent risk factors for poor medication adherence.Conclusion: Medication adherence in children with CPP is relatively better, and the factors leading to poor medication adherence are mainly on the caregivers of pediatric patients. It is recommended to increase the health education among caregivers of children with CPP to enhance the cognition of the condition and medication, and further improve the therapeutic efficacy for CPP.

The α-arrestins form a large family of evolutionally conserved modulators that control diverse signaling pathways, including both G-protein-coupled receptor (GPCR)-mediated and non-GPCR-mediated pathways, across eukaryotes. However, unlike β-arrestins, only a few α-arrestin targets and functions have been characterized. Here, using affinity purification and mass spectrometry, we constructed interactomes for 6 human and 12 Drosophila α-arrestins. The resulting high-confidence interactomes comprised 307 and 467 prey proteins in human and Drosophila, respectively. A comparative analysis of these interactomes predicted not only conserved binding partners, such as motor proteins, proteases, ubiquitin ligases, RNA splicing factors, and GTPase-activating proteins, but also those specific to mammals, such as histone modifiers and the subunits of V-type ATPase. Given the manifestation of the interaction between the human α-arrestin, TXNIP, and the histone-modifying enzymes, including HDAC2, we undertook a global analysis of transcription signals and chromatin structures that were affected by TXNIP knockdown. We found that TXNIP activated targets by blocking HDAC2 recruitment to targets, a result that was validated by chromatin immunoprecipitation assays. Additionally, the interactome for an uncharacterized human α-arrestin ARRDC5 uncovered multiple components in the V-type ATPase, which plays a key role in bone resorption by osteoclasts. Our study presents conserved and species-specific protein–protein interaction maps for α-arrestins, which provide a valuable resource for interrogating their cellular functions for both basic and clinical research.

Background Mitsugumin 53 (MG53) is a membrane repair factor that is associated with acute myocardial infarction. This study aimed to investigate the effects of MG53 on cardiomyocyte injury and the posttranslational modification of MG53. Methods Cardiomyocyte injury was evaluated by enzyme-linked immunosorbent assay and flow cytometry. The succinylation and ubiquitination levels of MG53 were examined by immunoprecipitation (IP) and western blot. The relationship between MG53 and KAT3B or SIRT7 was assessed by co-IP and immunofluorescence. Results The results showed that overexpression of MG53 inhibited inflammation response and apoptosis of cardiomyocytes induced by hypoxia/reoxygenation (H/R). Succinylation and protein levels of MG53 were downregulated in H/R-induced cells, which was inhibited by SIRT7 and promoted by KAT3B. SIRT7 aggravated and KAT3B alleviated MG53-mediated cardiomyocyte injury. Moreover, MG53 was succinylated and ubiquitinated at K130. Conclusion SIRT7 inhibited/KAT3B promoted succinylation of MG53 at K130 sites, which suppressed ubiquitination of MG53 and upregulated its protein levels, thereby alleviating H/R-induced cardiomyocyte injury. The findings suggested that MG53 may be a potential therapy for myocardial infarction.

AbstractLarge-scale farming is an important way for sustainable development of pig industry. In this regard, the digital economy has an important influence on the industrial structure and economic development, but whether it is conducive to large-scale pig farming (LSPF) needs further study. This study assesses the development level of the digital economy in 31 provinces of China and examines the transmission mechanism of the digital economy in LSPF. The results demonstrate that the digital economy can contribute both directly and indirectly to the LSPF through improved technological innovation, enhanced merchandise sales, and reduced labor costs of raising pigs. More importantly, the digital economy has a significant negative spatial spillover effect on LSPF; that is, it is not conducive to large-scale farming in neighboring localities. The results of the heterogeneity analysis further show that the digital economy is more significant for regions that have been identified as LSPF key and potential growth areas. The findings provide a reference for policymakers and professionals in emerging economies to facilitate the scale-up and sustainability of the pig industry.

The accumulation, processing and toxicity of Aβ can be affected by interacting with transthyretin (TTR). We obtained 31 compounds with different structures by virtual screening based on protein structure. Among them, compound 11 inhibited acid-induced TTR protein amyloid fibrils by 75.57 ​± ​11.27%, inhibited Aβ amyloid fibrils by 68.55 ​± ​0.81%, and promoted depolymerization of Aβ fibrils by 109.2 ​± ​7.9%. Surprisingly, this molecule, as a pharmacological chaperone of TTR/Aβ, bound to TTR and Aβ to form a ternary complex that promoted Aβ phagocytosis by microglia and attenuated Aβ neurotoxicity. These results together suggest that formation of the ternary complex [TTR+11] +Aβ may become a viable therapeutic approach for AD treatment.