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Background: Data on SARSCoV-2 infection in children with hematological malignancies (HM) are limited. Here, we describe the clinical features of children with HM after SARS-CoV-2 infection and investigate the potential risk factors for disease severity. Methods: Children with HM and SARS-CoV-2 infection from five hospitals in five cities in Henan, China from October 2022 to January 2023 were retrospectively included. Clinical information and Coronavirus disease 2019 (COVID-19) vaccination status were collected for further analyses. Results: A total of 285 children with HM and SARS-CoV-2 infections were included. COVID-19 was asymptomatic in 3.2% of the patients (n = 9), mild in 89.1% (n = 254), moderate in 5.3% (n = 15), severe in 1.8% (n = 5), and critical in 0.7% (n = 2). Fever (92.4%) and cough (56.9%) were the most common symptoms. Most (249, 88.3%) children were managed at home during their COVID-19 illness. Of the 36 children admitted to the hospital, two required intensive care unit care, 11 required supplementary oxygen, and two non-invasive ventilation. A total of 283 (99.3%) children fully recovered and two (0.7%) died due to COVID-19. Significant risk factors for increased severity of infection in multivariable analyses were the presence of comorbidity (OR, 10.4; 95%CI, 2.8–38.7; p

Abstract Background Pulmonary fibrosis (PF) is an aging-related progressive lung disorder. The aged lung undergoes functional and structural changes termed immunosenescence and inflammaging, which facilitate the occurrence of fibrosis. Interleukin-10 (IL-10) is a potent anti-inflammatory and immunoregulatory cytokine, yet it remains unclear how IL-10 deficiency-induced immunosenescence participates in the development of PF. Methods Firstly we evaluated the susceptibility to fibrosis and IL-10 expression in aged mice. Then 13-month-old wild-type (WT) and IL-10 knockout (KO) mice were subjected to bleomycin(BLM) and analyzed senescence-related markers by PCR, western blot and immunohistochemistry staining of p16, p21, p53, as well as DHE and SA-β-gal staining. We further compared 18-month-old WT mice with 13-month-old IL-10KO mice to assess aging-associated cell senescence and inflamation infiltration in both lung and BALF. Moreover, proliferation and apoptosis of alveolar type 2 cells(AT2) were evaluated by FCM, immunofluorescence, TUNEL staining, and TEM analysis. Recombinant IL-10 (rIL-10) was also administered intratracheally to evaluate its therapeutic potential and related mechanism. For the in vitro experiments, 10-week-old naïve pramily lung fibroblasts(PLFs) were treated with the culture medium of 13-month PLFs derived from WT, IL-10KO, or IL-10KO + rIL-10 respectively, and examined the secretion of senescence-associated secretory phenotype (SASP) factors and related pathways. Results The aged mice displayed increased susceptibility to fibrosis and decreased IL-10 expression. The 13-month-old IL-10KO mice exhibited significant exacerbation of cell senescence compared to their contemporary WT mice, and even more severe epithelial-mesenchymal transition (EMT) than that of 18 month WT mice. These IL-10 deficient mice showed heightened inflammatory responses and accelerated PF progression. Intratracheal administration of rIL-10 reduced lung CD45 + cell infiltration by 15%, including a 6% reduction in granulocytes and a 10% reduction in macrophages, and increased the proportion of AT2 cells by approximately 8%. Additionally, rIL-10 significantly decreased α-SMA and collagen deposition, and reduced the expression of senescence proteins p16 and p21 by 50% in these mice. In vitro analysis revealed that conditioned media from IL-10 deficient mice promoted SASP secretion and upregulated senescence genes in naïve lung fibroblasts, which was mitigated by rIL-10 treatment. Mechanistically, rIL-10 inhibited TGF-β-Smad2/3 and PTEN/PI3K/AKT/ERK pathways, thereby suppressing senescence and fibrosis-related proteins. Conclusions IL-10 deficiency in aged mice leads to accelerated cell senescence and exacerbated fibrosis, with IL-10KO-PLFs displaying increased SASP secretion. Recombinant IL-10 treatment effectively mitigates these effects, suggesting its potential as a therapeutic target for PF. Graphical Abstract

Abstract Background Abiotic stress seriously affects the growth and yield of crops. It is necessary to search and utilize novel abiotic stress resistant genes for 2.0 breeding programme in quinoa. In this study, the impact of drought stress on glucose metabolism were investigated through transcriptomic and metabolomic analyses in quinoa seeds. Candidate drought tolerance genes on glucose metabolism pathway were verified by qRT-PCR combined with yeast expression system. Results From 70 quinoa germplasms, drought tolerant material M059 and drought sensitive material M024 were selected by comprehensive evaluation of drought resistance. 7042 differentially expressed genes (DEGs) were indentified through transcriptomic analyses. Gene Ontology (GO) analysis revealed that these DEGs were closely related to carbohydrate metabolic process, phosphorus-containing groups, and intracellular membrane-bounded organelles. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis detected that DEGs were related to pathways involving carbohydrate metabolisms, glycolysis and gluconeogenesis. Twelve key differentially accumulated metabolites (DAMs), (D-galactose, UDP-glucose, succinate, inositol, D-galactose, D-fructose-6-phosphate, D-glucose-6-phosphate, D-glucose-1-phosphate, dihydroxyacetone phosphate, ribulose-5-phosphate, citric acid and L-malate), and ten key candidate DEGs (CqAGAL2, CqINV, CqFrK7, CqCELB, Cqbg1x, CqFBP, CqALDO, CqPGM, CqIDH3, and CqSDH) involved in drought response were identified. CqSDH, CqAGAL2, and Cqβ-GAL13 were candidate genes that have been validated in both transcriptomics and yeast expression screen system. Conclusion These findings provide a foundation for elucidating the molecular regulatory mechanisms governing glucose metabolism in quinoa seeds under drought stress, providing insights for future research exploring responses to drought stress in quinoa.

Abstract Background Ochrobactrum anthropi is widely distributed and primarily infects patients with compromised immune functions . Historically, O. anthropi has been considered to possess low toxicity and pathogenicity; however, recent studies suggest that it may in fact cause severe purulent infections. In this case study, we examine a case of O. anthropi infection following corneal transplantation, exploring the occurrence and outcomes of such post-operative infections. Case presentation A retrospective analysis of cases involved examinations, genetic testing for diagnosis, and subsequent treatment. In patients undergoing partial penetrating keratoplasty with a fungal corneal ulcer perforation, anterior chamber exudation and purulence were observed post-surgery. Despite antifungal treatment, genetic testing of the anterior chamber fluid and purulent material confirmed O. anthropi infection. The use of antimicrobial treatment specifically targeting O. anthropi was found to be effective in treating the infection. Conclusion Inflammatory reactions following corneal transplantation should be should be monitored for the presence of other infections. Genetic testing has significant implications for clinical diagnosis and treatment.

Slope shape as a consequence of erosional landform development plays a prominent role in soil erosion. Clarifying the distribution of soil erosion and deposition patterns on different shaped slopes is crucial for soil erosion control. The aim of this study was to decipher the effects of slope shape on soil erosion and deposition patterns under natural rainfall conditions based on high-resolution unmanned aerial vehicle (UAV) data and geographic information system technology. Structure from motion (SfM)-UAV photogrammetry was carried out in four runoff plots with various slope shapes during the rainy season in 2021. Digital elevation models (DEMs) were developed for each slope shape before and after the rainy season. In addition to collecting runoff and sediment, the DEMs of difference were analyzed to quantify soil erosion and deposition patterns on various slope shapes in the rainy season. Results showed that the runoff volumes and sediment yields induced by rainfall were markedly different among various slope shapes. The mean runoff volume and sediment yield from the concave-convex slope were 1.09 ∼ 2.69 and 1.33 ∼ 27.16 times those of the other three slopes, respectively, with less sediment loss from the convex-concave slope and its combination slope. Slope shape exhibited a notable effect on the type of slope erosion and deposition. All four slopes showed considerable changes in surface elevation after the rainy season. The increase and decrease in surface elevation were concentrated in the range of –0.02 to –0.007 m and 0.007 to 0.02 m, respectively, with a low proportion of changes less than –0.03 m and greater than 0.03 m. The effectiveness of SfM-UAV in monitoring the microgeomorphic changes of slopes was verified by the consistency of soil erosion amounts based on sediment collection and SfM-UAV measurements. Reference values were provided to solve the threshold problem of slope length cutoff in soil erosion prediction models based on runoff plot experiments. Findings of this study could be useful for decision-making in soil erosion control and slope reconstruction.

The traditional stir-fry process before pressing is crucial to manufacture Hainan camellia oil. To assess the effects of the stir-fry process on Hainan camellia oil, six samples across different stir-fry stages were analyzed. The stir-fry process modified odors, volatile metabolite profiles, and human health-promoting functions of Hainan camellia oil. Totally, 350 volatile metabolites were detected, and heterocyclic compounds were revealed as the main contributors of strong aroma. Potential indicators for monitoring the stir-fry degree were established. Eight key aroma volatile metabolites were identified, including three new ones (1-octen-3-one, 2,3-butanedione, and vanillin). Lipids degradation and the Millard reaction are probably the main pathways for aroma generation. Over-stir-fry treatment diminished the contents of some important volatile metabolites but increased the risk of arising burnt odor. Our work offered insights into the effects of the stir-fry process and over-stir-fry treatment on Hainan camellia oil, which is meaningful for improving the hot-pressing technique.

Abstract Almost all the neutralizing antibodies targeting the receptor-binding domain (RBD) of spike (S) protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged or emerging variants, such as Omicron and its sub-variants. This suggests that highly conserved epitopes are crucial for the development of neutralizing antibodies. Here, we present one nanobody, N235, displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants, including the newly emerged Omicron and its sub-variants. Cryo-electron microscopy demonstrates N235 binds a novel, conserved, cryptic epitope in the N-terminal domain (NTD) of the S protein, which interferes with the RBD in the neighboring S protein. The neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S complex. Furthermore, a nano-IgM construct (MN235), engineered by fusing N235 with the human IgM Fc region, displays prevention via inducing S1 shedding and cross-linking virus particles. Compared to N235, MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in vitro. The intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo, suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.

Objective: To determine the active components of Eupolyphaga sinensis Walker (Tu Bie Chong) and explore the mechanisms underlying its fracture-healing ability. Methods: A modified Einhorn method was used to develop a rat tibial fracture model. Progression of bone healing was assessed using radiological methods. Safranin O/fast green and CD31 immunohistochemical staining were performed to evaluate the growth of bone cells and angiogenesis at the fracture site. Methylthiazoletetrazolium blue and wound healing assays were used to analyze cell viability and migration. The Transwell assay was used to explore the invasion capacity of the cells. Tubule formation assays were used to assess the angiogenesis capacity of human vascular endothelial cells (HUVECs). qRT-PCR was used to evaluate the changes in gene transcription levels. Results: Tu Bie Chong fraction 3 (TF3) significantly shortened the fracture healing time in model rats. X-ray results showed that on day 14, fracture healing in the TF3 treatment group was significantly better than that in the control group (P = .0086). Tissue staining showed that cartilage growth and the number of H-shaped blood vessels at the fracture site of the TF3 treatment group were better than those of the control group. In vitro, TF3 significantly promoted the proliferation and wound healing of MC3T3-E1s and HUVECs (all P

Abstract Coherent spin waves possess immense potential in wave-based information computation, storage, and transmission with high fidelity and ultra-low energy consumption. However, despite their seminal importance for magnonic devices, there is a paucity of both structural prototypes and theoretical frameworks that regulate the spin current transmission and magnon hybridization mediated by coherent spin waves. Here, we demonstrate reconfigurable coherent spin current transmission, as well as magnon–magnon coupling, in a hybrid ferrimagnetic heterostructure comprising epitaxial Gd3Fe5O12 and Y3Fe5O12 insulators. By adjusting the compensated moment in Gd3Fe5O12, magnon–magnon coupling was achieved and engineered with pronounced anticrossings between two Kittel modes, accompanied by divergent dissipative coupling approaching the magnetic compensation temperature of Gd3Fe5O12 (T M,GdIG), which were modeled by coherent spin pumping. Remarkably, we further identified, both experimentally and theoretically, a drastic variation in the coherent spin wave-mediated spin current across T M,GdIG, which manifested as a strong dependence on the relative alignment of magnetic moments. Our findings provide significant fundamental insight into the reconfiguration of coherent spin waves and offer a new route towards constructing artificial magnonic architectures.

Abstract Antibody–drug conjugates (ADCs) consist of monoclonal antibodies that target tumor cells and cytotoxic drugs linked through linkers. By leveraging antibodies’ targeting properties, ADCs deliver cytotoxic drugs into tumor cells via endocytosis after identifying the tumor antigen. This precise method aims to kill tumor cells selectively while minimizing harm to normal cells, offering safe and effective therapeutic benefits. Recent years have seen significant progress in antitumor treatment with ADC development, providing patients with new and potent treatment options. With over 300 ADCs explored for various tumor indications and some already approved for clinical use, challenges such as resistance due to factors like antigen expression, ADC processing, and payload have emerged. This review aims to outline the history of ADC development, their structure, mechanism of action, recent composition advancements, target selection, completed and ongoing clinical trials, resistance mechanisms, and intervention strategies. Additionally, it will delve into the potential of ADCs with novel markers, linkers, payloads, and innovative action mechanisms to enhance cancer treatment options. The evolution of ADCs has also led to the emergence of combination therapy as a new therapeutic approach to improve drug efficacy.

ABSTRACT The rapid expansion of antibiotic-resistant bacterial diseases is a global burden on public health. It makes sense to repurpose and reposition already-approved medications for use as supplementary agents in synergistic combinations with existing antibiotics. Here, we demonstrate that the anthelmintic drug nitazoxanide (NTZ) synergistically enhances the effectiveness of the lipopeptide antibiotic polymyxin B in inhibiting gram-negative bacteria, including those resistant to polymyxin B. Mechanistic investigations revealed that nitazoxanide inhibited calcium influx and cell membrane depolarization, enhanced the affinity between polymyxin B and the extracellular membrane, and promoted intracellular ATP depletion and an increase in reactive oxygen species (ROS), thus enhancing the penetration and disruption of the Escherichia coli cell membrane by polymyxin B. The transcriptomic analysis revealed that the combination resulted in energy depletion by inhibiting both aerobic and anaerobic respiration patterns in bacterial cells. The increased bactericidal effect of polymyxin B on the E. coli ∆nuoC strain further indicates that NuoC could be a promising target for nitazoxanide. Furthermore, the combination of nitazoxanide and polymyxin B showed promising therapeutic effects in a mouse infection model infected with E. coli. Taken together, these results demonstrate the potential of nitazoxanide as a novel adjuvant to polymyxin B, to overcome antibiotic resistance and improve therapeutic outcomes in refractory infections.IMPORTANCEThe rapid spread of antibiotic-resistant bacteria poses a serious threat to public health. The search for potential compounds that can increase the antibacterial activity of existing antibiotics is a promising strategy for addressing this issue. Here, the synergistic activity of the FDA-approved agent nitazoxanide (NTZ) combined with polymyxin B was investigated in vitro using checkerboard assays and time-kill curves. The synergistic mechanisms of the combination of nitazoxanide and polymyxin B were explored by fluorescent dye, transmission electron microscopy (TEM), and transcriptomic analysis. The synergistic efficacy was evaluated in vivo by the Escherichia coli and mouse sepsis models. These results suggested that nitazoxanide, as a promising antibiotic adjuvant, can effectively enhance polymyxin B activity, providing a potential strategy for treating multidrug-resistant bacteria.

Abstract Background More than half of the global population lives in areas at risk of dengue (DENV) transmission. Developing an efficient risk prediction system can help curb dengue outbreaks, but multiple variables, including mosquito-based surveillance indicators, still constrain our understanding. Mosquito or oviposition positive index (MOI) has been utilized in field surveillance to monitor the wild population density of Aedes albopictus in Guangzhou since 2005. Methods Based on the mosquito surveillance data using Mosq-ovitrap collection and human landing collection (HLC) launched at 12 sites in Guangzhou from 2015 to 2017, we established a MOI-based model of the basic dengue reproduction number (R 0) using the classical Ross-Macdonald framework combined with a linear mixed-effects model. Results During the survey period, the mean MOI and adult mosquito density index (ADI) using HLC for Ae. albopictus were 12.96 ± 17.78 and 16.79 ± 55.92, respectively. The R 0 estimated from the daily ADI (ADID) showed a significant seasonal variation. A 10-unit increase in MOI was associated with 1.08-fold (95% CI 1.05, 1.11) ADID and an increase of 0.14 (95% CI 0.05, 0.23) in the logarithmic transformation of R 0. MOI-based R 0 of dengue varied by month and average monthly temperature. During the active period of Ae. albopictus from April to November in Guangzhou region, a high risk of dengue outbreak was predicted by the MOI-based R 0 model, especially from August to October, with the predicted R 0 > 1. Meanwhile, from December to March, the estimates of MOI-based R 0 were < 1. Conclusions The present study enriched our knowledge about mosquito-based surveillance indicators and indicated that the MOI of Ae. albopictus could be valuable for application in estimating the R 0 of dengue using a statistical model. The MOI-based R 0 model prediction of the risk of dengue transmission varied by month and temperature in Guangzhou. Our findings lay a foundation for further development of a complex efficient dengue risk prediction system. Graphical Abstract

Abstract Estrogens promote binge alcohol drinking and contribute to sex differences in alcohol use disorder. However, the mechanisms are largely unknown. This study aims to test if estrogens act on 5-hydroxytryptamine neurons in the dorsal raphe nucleus (5-HTDRN) to promote binge drinking. We found that female mice drank more alcohol than male mice in chronic drinking in the dark (DID) tests. This sex difference was associated with distinct alterations in mRNA expression of estrogen receptor α (ERα) and 5-HT-related genes in the DRN, suggesting a potential role of estrogen/ERs/5-HT signaling. In supporting this view, 5-HTDRN neurons from naïve male mice had lower baseline firing activity but higher sensitivity to alcohol-induced excitation compared to 5-HTDRN neurons from naïve female mice. Notably, this higher sensitivity was blunted by 17β-estradiol treatment in males, indicating an estrogen-dependent mechanism. We further showed that both ERα and ERβ are expressed in 5-HTDRN neurons, whereas ERα agonist depolarizes and ERβ agonist hyperpolarizes 5-HTDRN neurons. Notably, both treatments blocked the stimulatory effects of alcohol on 5-HTDRN neurons in males, even though they have antagonistic effects on the activity dynamics. These results suggest that ERs’ inhibitory effects on ethanol-induced burst firing of 5-HTDRN neurons may contribute to higher levels of binge drinking in females. Consistently, chemogenetic activation of ERα- or ERβ-expressing neurons in the DRN reduced binge alcohol drinking. These results support a model in which estrogens act on ERα/β to prevent alcohol-induced activation of 5-HTDRN neurons, which in return leads to higher binge alcohol drinking.

Abstract Lumbar disc herniation (LDH) is a clinically common degenerative disease of the spine, and spinal–pelvic sagittal balance and paravertebral muscle degeneration have been a research focus in recent years. To explore the relationship between the degeneration of paravertebral muscle and the changes in the spinal–pelvic sagittal parameters in LDH patients, 105 LDH patients (experimental group) and 63 healthy volunteers (control group) hospitalized in Ordos Central Hospital from January 2020 and January 2023 were included as study subjects. All the patients underwent lumbar magnetic resonance imaging and spinal X-ray using uniform criteria. The correlation between the paravertebral muscle and sagittal–pelvic sagittal parameters of the patients with LDH was obtained from two imaging examinations, and the data were organized and grouped to explore the correlation between these parameters. No significant difference in general data existed between the groups (P > 0.05). In the L4/5 LDH patients group, the ratio of fat infiltration (FIR) in the healthy side [multifidus (MF) and erector spinae (ES)] was negatively correlated with the lumbar lordosis (LL) (r = −0.461, r = −0.486, P

Soil surface roughness (SSR) is an important factor affecting soil erosion and soil nutrient transport. Human tillage leads to increased instability in SSR, and the characteristics of SSR caused by different tillage practices await further study. This research utilizes terrestrial laser scanning (TLS) to measure the SSR of six farmland plots (25 m × 25 m) and analyzes the characteristics of SSR under different tillage practices (plowing, harrowing, ridging, crusting, etc.). The study results show: 1) Different agricultural tillage practices lead to significant differences in SSR. The plowed and harrowed plot corresponds to the maximum (2.49 cm) and minimum (1.5 cm) root mean square height (RMSH), respectively. Correlation length (CL) is more affected by different tillage practices than RMSH. The difference in CL between the ridged and harrowed plot is 2.6 times. 2) Ridging and crusting caused significant directional variation in SSR. The SSR anisotropy of the harrowed plot can be disregarded. 3) Under the condition of measuring soil profile in 12 directions and randomly sampling 70 times in each direction, the profile length must be at least 3 m to ensure that the measurement error of SSR is better than 5% compared to the “true” value. TLS can measure two-dimensional SSR. Therefore, it is only necessary to ensure that the measurement range is at least 3 m × 3 m. The study results provide a reference for the high-precision measurement of SSR (RMSH and CL) under different agricultural tillage practices.

Abstract Background Abdominal distension is a relatively common complication in postoperative lung cancer patients, which affects patients’ early postoperative recovery to varying degrees. However, the current status of the incidence of abdominal distension in postoperative lung cancer patients and the affecting factors are not well understood. This study aims at exploring the incidence of abdominal distension in postoperative lung cancer patients in ICU based on real-world data and analyzing its influencing factors. Methods A retrospective cohort study was conducted, encompassing patients who underwent lung cancer resections in the Lung Cancer Center of West China Hospital of Sichuan University from April 2020 to April 2021. Nevertheless, patients younger than 18 years and those whose information was limited in medical records were excluded. All data were obtained from the hospital HIS system. In this study, the influencing factors of abdominal distension were analyzed by univariate analysis and multiple logistic regression methods. Results A total of 1317 patients met eligibility criteria, and were divided into the abdominal distended group and the non-distended group according to whether abdominal distension occurred after surgery. Abdominal distension occurred in a total of 182 cases(13.8%). The results of the univariate analysis showed that, compared with the non-distended group, the abdominal distended group had these features as follows: more women (P = 0.021), older (P = 0.000), lower BMI (P = 0.000), longer operation duration (P = 0.031), more patients with open thoracotomy (P = 0.000), more patients with pneumonectomy (p = 0.002), more patients with neoadjuvant chemotherapy (P = 0.000), more days of hospitalization on average (P = 0.000), and higher costs of hospitalization on average (P = 0.032). Multifactor logistic regression analysis showed that sex (OR = 0.526; 95% CI = 0.378 ~0.731), age (OR = 1.154; 95%CI = 1.022 ~1.304) and surgical approach (OR = 4.010; 95%CI = 2.781 ~5.781) were independent influencing factors for the occurrence of abdominal distension in patients after lung cancer surgery in ICU. Conclusions The incidence of abdominal distension was high in postoperative lung cancer patients in ICU, and female, older and patients with open thoracotomy were more likely to experience abdominal distension. Trial registration The study was approved by the Chinese Clinical Trials Registry (registration number was ChiCTR2200061370).

Objective This study aimed to compare the effectiveness of instant versus text messaging intervention (TMI) on antiretroviral therapy (ART) adherence among men who have sex with men (MSM) living with HIV. Methods This study was conducted in an infectious disease hospital of Jinan, China from October 2020 to June 2021, using non-randomized concurrent controlled design to compare the effectiveness of instant messaging intervention (IMI) versus TMI. The intervention strategies (health messaging, medication reminder, and peer education) and contents were consistent between the two groups, and the difference was service delivery method and type of information. The primary outcome was the proportion of achieving optimal ART adherence, defined as never missing any doses and delayed any doses more than 1 hour. Results A total of 217 participants (including 72 in TMI group and 145 in IMI group) were included in the study. The proportion of achieving optimal adherence was higher in IMI group than TMI group at the first follow-up (90.2% versus 77.6%, p = 0.021) and second follow-up (86.5% versus 76.6%, p = 0.083). The effect of IMI versus TMI on improving ART adherence was found not to be statistically significant (risk ratio (RR) = 1.93, 95% confidence interval (CI): 0.95–3.94) in complete-case analysis. However, when excluding participants who did not adhere to the interventions, a significant improvement was observed (RR = 2.77, 95%CI: 1.21–6.38). More participants in IMI group expressed highly rated satisfaction to the intervention services than those in TMI group (67.3% versus 50.0%). Conclusions The IMI demonstrated superior efficacy over TMI in improving ART adherence and satisfaction with intervention services. It is suggested that future digital health interventions targeting ART adherence should prioritize instant messaging with multimedia information in areas with Internet access. Trial registration The study was registered at the Chinese Clinical Trial Register (ChiCTR), with number [ChiCTR2000041282].

Summary: Background: Hospitals in China are classified into tiers (1, 2 or 3), with the largest (tier 3) having more equipment and specialist staff. Differential health insurance cost-sharing by hospital tier (lower deductibles and higher reimbursement rates in lower tiers) was introduced to reduce overcrowding in higher tier hospitals, promote use of lower tier hospitals, and limit escalating healthcare costs. However, little is known about the effects of differential cost-sharing in health insurance schemes on choice of hospital tiers. Methods: In a 9-year follow-up of a prospective study of 0.5 M adults from 10 areas in China, we examined the associations between differential health insurance cost-sharing and choice of hospital tiers for patients with a first hospitalisation for stroke or ischaemic heart disease (IHD) in 2009–2017. Analyses were performed separately in urban areas (stroke: n = 20,302; IHD: n = 19,283) and rural areas (stroke: n = 21,130; IHD: n = 17,890), using conditional logit models and adjusting for individual socioeconomic and health characteristics. Findings: About 64–68% of stroke and IHD cases in urban areas and 27–29% in rural areas chose tier 3 hospitals. In urban areas, higher reimbursement rates in each tier and lower tier 3 deductibles were associated with a greater likelihood of choosing their respective hospital tiers. In rural areas, the effects of cost-sharing were modest, suggesting a greater contribution of other factors. Higher socioeconomic status and greater disease severity were associated with a greater likelihood of seeking care in higher tier hospitals in urban and rural areas. Interpretation: Patient choice of hospital tiers for treatment of stroke and IHD in China was influenced by differential cost-sharing in urban areas, but not in rural areas. Further strategies are required to incentivise appropriate health seeking behaviour and promote more efficient hospital use. Funding: Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, China Ministry of Science and Technology, and National Natural Science Foundation of China.

Abstract Background Aedes albopictus is an invasive vector of serious Aedes-borne diseases of global concern. Habitat management remains a critical factor for establishing a cost-effective systematic strategy for sustainable vector control. However, the community-based characteristics of Ae. albopictus habitats in complex urbanization ecosystems are still not well understood. Methods A large-scale investigation of aquatic habitats, involving 12 sites selected as representative of four land use categories at three urbanization levels, was performed in Guangzhou, China during 2015–2017. The characteristics and dynamics of these Ae. albopictus habitats were assessed using habitat-type composition, habitat preference, diversity indexes and the Route index (RI), and the temporal patterns of these indexes were evaluated by locally weighted scatterplot smoothing models. The associations of RI with urbanization levels, land use categories and climatic variables were inferred using generalized additive mixed models. Results A total of 1994 potential habitats and 474 Ae. albopictus-positive habitats were inspected. The majority of these habitats were container-type habitats, with Ae. albopictus showing a particularly higher habitat preference for plastic containers, metal containers and ceramic vessels. Unexpectedly, some non-container-type habitats, especially ornamental ponds and surface water, were found to have fairly high Ae. albopictus positivity rates. Regarding habitats, the land use category residential and rural in Jiangpu (Conghua District, Guangzhou) had the highest number of Ae. albopictus habitats with the highest positive rates. The type diversity of total habitats (H-total) showed a quick increase from February to April and peaked in April, while the H-total of positive habitats (H-positive) and RIs peaked in May. RIs mainly increased with the monthly average daily mean temperature and monthly cumulative rainfall. We also observed the accumulation of diapause eggs in the winter and diapause termination in the following March. Conclusions Ecological heterogeneity of habitat preferences of Ae. albopictus was demonstrated in four land use categories at three urbanization levels. The results reveal diversified habitat-type compositions and significant seasonal variations, indicating an ongoing adaptation of Ae. albopictus to the urbanization ecosystem. H-positivity and RIs were inferred as affected by climatic variables and diapause behavior of Ae. albopictus, suggesting that an effective control of overwintering diapause eggs is crucial. Our findings lay a foundation for establishing a stratified systematic management strategy of Ae. albopictus habitats in cities that is expected to complement and improve community-based interventions and sustainable vector management. Graphical Abstract

CO2 is one of the primary greenhouse gases impacting global climate change, making it crucial to understand the spatiotemporal variations of CO2. Currently, commonly used satellites serve as the primary means of CO2 observation, but they often suffer from striping issues and fail to achieve complete coverage. This paper proposes a method for constructing a comprehensive high-spatiotemporal-resolution XCO2 dataset based on multiple auxiliary data sources and satellite observations, utilizing multiple simple deep neural network (DNN) models. Global validation results against ground-based TCCON data demonstrate the excellent accuracy of the constructed XCO2 dataset (R is 0.94, RMSE is 0.98 ppm). Using this method, we analyze the spatiotemporal variations of CO2 in China and its surroundings (region: 0°–60° N, 70°–140° E) from 2019 to 2020. The gapless and fine-scale CO2 generation method enhances people’s understanding of CO2 spatiotemporal variations, supporting carbon-related research.

Abstract Pulmonary fibrosis (PF) is a serious progressive fibrotic disease that is characterized by excessive accumulation of extracellular matrix (ECM), thus resulting in stiff lung tissues. Lysyl oxidase (LOX) is an enzyme involved in fibrosis by catalyzing collagen cross-linking. Studies found that the ingredients in schisandra ameliorated bleomycin (BLM)-induced PF, but it is unknown whether the anti-PF of schisandra is related to LOX. In this study, we established models of PF including a mouse model stimulated by BLM and a HFL1 cell model induced by transforming growth factor (TGF)-β1 to evaluate the inhibition effects of Schisandrin C (Sch C) on PF. We observed that Sch C treatment decreased pulmonary indexes compared to control group. Treatment of Sch C showed a significant reduction in the accumulation of ECM as evidenced by decreased expressions of α-SMA, FN, MMP2, MMP9, TIMP1 and collagen proteins such as Col 1A1, and Col 3A1. In addition, the expression of LOX in the lung tissue of mice after Sch C treatment was effectively decreased compared with the MOD group. The inhibition effects in vitro were consistent with those in vivo. Mechanistic studies revealed that Sch C significantly inhibited TGF-β1/Smad2/3 and TNF-α/JNK signaling pathways. In conclusion, our data demonstrated that Sch C significantly ameliorated PF in vivo and vitro, which may play an important role by reducing ECM deposition and inhibiting the production of LOX.

Abstract Segmentations provide important clues for diagnosing diseases. U‐shaped neural networks with skip connections have become one of popular frameworks for medical image segmentation. Skip connections really reduce loss of spatial details caused by down‐sampling, but they cannot handle well semantic gaps between low‐ and high‐level features. It is quite challenging to accurately separate out long, narrow, and small organs from human bodies. To solve these problems, the authors propose a Multiple Gated Boosting Network (MGB‐Net). To boost spatial accuracy, the authors first adopt Gated Recurrent Units (GRU) to design multiple Gated Skip Connections (GSC) at different levels, which efficiently reduce the semantic gap between the shallow and deep features. The Update and Reset gates of GRUs enhance features beneficial to segmentation and suppress information adverse to final results in a recurrent way. To obtain more scale invariances, the authors propose a module of Multi‐scale Weighted Channel Attention (MWCA). The module first uses convolutions with different kernel sizes and group numbers to generate multi‐scale features, and then adopts learnable weights to emphasize the importance of each scale for capturing attention features. Blocks of Transformer Self‐Attention (TSA) are sequentially stacked to extract long‐range dependency features. To effectively fuse and boost the features of MWCA and TSA, the authors use GRUs again to propose a Gated Dual Attention module (GDA), which enhances beneficial features and suppresses adverse information in a gated learning way. Experiments show that the authors’ method achieves an average Dice coefficient of 80.66% on the Synapse multi‐organ segmentation dataset. The authors’ method outperforms the state‐of‐the‐art methods on medical images. In addition, the authors’ method achieves a Dice segmentation accuracy of 62.77% on difficult objects such as pancreas, significantly exceeding the current average accuracy, so multiple gated boosting (MGB) methods are reliably effective for improving the ability of feature representations. The authors’ code is publicly available at https://github.com/DAgalaxy/MGB‐Net.

Abstract Uncontrolled viral replication and excessive inflammation are the main causes of death in the host infected with virus. Hence inhibition of intracellular viral replication and production of innate cytokines, which are the key strategies of hosts to fight virus infections, need to be finely tuned to eliminate viruses while avoid harmful inflammation. The E3 ligases in regulating virus replication and subsequent innate cytokines production remain to be fully characterized. Here we report that the deficiency of the E3 ubiquitin-protein ligase HECTD3 results in accelerated RNA virus clearance and reduced inflammatory response both in vitro and in vivo. Mechanistically, HECTD3 interacts with dsRNA-dependent protein kinase R (PKR) and mediates Lys33-linkage of PKR, which is the first non-proteolytic ubiquitin modification for PKR. This process disrupts the dimerization and phosphorylation of PKR and subsequent EIF2α activation, which results in the acceleration of virus replication, but promotes the formation of PKR-IKK complex and subsequent inflammatory response. The finding suggests HECTD3 is the potential therapeutic target for simultaneously restraining RNA virus replication and virus-induced inflammation once pharmacologically inhibited.

Abstract High-quality ground observation networks are an important basis for scientific research. Here, an automatic soil observation network for high-resolution satellite applications in China (SONTE-China) was established to measure both pixel- and multilayer-based soil moisture and temperature. SONTE-China is distributed across 17 field observation stations with a variety of ecosystems, covering both dry and wet zones. In this paper, the average root mean squared error (RMSE) of station-based soil moisture for well-characterized SONTE-China sites is 0.027 m3/m3 (0.014~0.057 m3/m3) following calibration for specific soil properties. The temporal and spatial characteristics of the observed soil moisture and temperature in SONTE-China conform to the geographical location, seasonality and rainfall of each station. The time series Sentinel-1 C-band radar signal and soil moisture show strong correlations, and the RMSE of the estimated soil moisture from radar data was lower than 0.05 m3/m3 for the Guyuan and Minqin stations. SONTE-China is a soil moisture retrieval algorithm that can validate soil moisture products and provide basic data for weather forecasting, flood forecasting, agricultural drought monitoring and water resource management.

Abstract Background The optimal timing of endoscopy in liver cirrhosis with acute variceal bleeding (AVB) remains controversial in current guidelines and studies. Methods Consecutive patients with liver cirrhosis and AVB were screened. The timing of endoscopy was calculated from the last presentation of AVB or the admission to endoscopy. Early endoscopy was defined as the interval

Abstract Carbon-based solid acids have been successfully employed as acidic catalysts for pollutant mitigation in wastewater. To fully tap the potentials of commercially viable carbons for the preparation of solid acids and enhance their catalytic performances is a challenging problem. In this work, three commercialized carbons including biochar, activated carbon and graphite were preprocessed (ball-milling, Hummer exfoliation, HNO3 soaking, and microwave heating in HNO3, etc.), sulfonated, and evaluated as solid-acid catalysts for tylosin mitigation. Graphite-originated solid acid performed the best through a balling-milling preprocess, while biochar-originated solid acids behaved well under all preprocessing treatments, in which 40 mg L−1 of tylosin was mitigated within 8 min by 1 g L−1 of biochar-originated solid acids. The biochar solid acid through the ball-milling preprocess presented high total acidity and large amounts of –SO3H groups, due to dramatically increased surface area and the rise of activation groups (hydroxyl, alkyl and alkoxy groups, etc.) facilitating electrophilic reaction. In addition, decreased particle size and aromaticity and increased structural defects also contributed. Theoretical calculation of average local ionization energy (ALIE) of condensed aromatic model molecules with substituted activation groups confirmed the promoting effects on sulfonation from strong to weak were 8.40–9.06 eV. These findings have deepened the knowledge in tuning carbon surface chemistry for better sulfonation, thus strengthening catalytic degradation of tylosin. The value of this study is in pulling a clear thread for maneuvering solid-acid catalysts using carbons, which holds a novel promise for rationally functionalizing biochar-based catalysts for the remediation of macrolide antibiotics in polluted water. Graphical Abstract

Rock fragments are an important component of soil, and their presence has a significant impact on soil erosion and sediment yield. In this paper, the effects of rock fragments in the topsoil profile (RFP) and rock fragments on the soil surface (RFS) on the soil erodibility factor (K) were assessed at a global scale. The spatial pattern of the relationship between stoniness and erodibility (RS-K) and its predominant factors were explored through correlation analysis, pattern analysis, and random forest model analysis. The results were as followings: (1) The existence of RFP increased K by 2.84%. The RFS of the mountain land and desert/Gobi reduced K by 18.7%; therefore, once the RFP and RFS were taken into account in the calculation, K was 6.98% lower. (2) The predominant factors of the effect of RFS and the joint effect of RFP and RFS were elevation and slope gradient. The predominant factors of the effect of RFP were annual average precipitation and annual average temperature. (3) In assessing and mapping soil erosion in large regions, special attention should be given to areas with large rock fragment contents, a relatively high altitude, and the presence of steep slope. If rock fragments were not taken into consideration, the mapping results of soil erosion may be biased. This article made the calculation of K more complete and accurate, thereby improving the accuracy of regional soil erosion estimation. This research was of significance for the investigation of global hydrological effects and simulation of the global soil carbon budget.

Vegetation classification has always been the focus of remote sensing applications, especially for tropical regions with fragmented terrain, cloudy and rainy climates, and dense vegetation. How to effectively classify vegetation in tropical regions by using multi-spectral remote sensing with high resolution and red-edge spectrum needs to be further verified. Based on the experiment in Wenchang, Hainan, China, which is located in the tropical monsoon region, and combined with the ZY-1 02D 2.5 m fused images in January, March, July, and August, this paper discusses whether NDVI and four red-edge vegetation indices (VIs), CIre, NDVIre, MCARI, and TCARI, can promote vegetation classification and reduce the saturation. The results show that the schemes with the highest classification accuracies in all phases are those in which the red-edge VIs are involved, which suggests that the red-edge VIs can effectively contribute to the classification of vegetation. The maximum accuracy of the single phase is 86%, and the combined accuracy of the four phases can be improved to 92%. It has also been found that CIre and NDVIre do not reach saturation as easily as NDVI and MCARI in July and August, and their ability to enhance the separability between different vegetation types is superior to that of TCARI. In general, red-edge VIs can effectively promote vegetation classification in tropical monsoon regions, and red-edge VIs, such as CIre and NDVIre, have an anti-saturation performance, which can slow down the confusion between different vegetation types due to saturation.

The utilization of remote sensing soil moisture products in agricultural and hydrological studies is on the rise. Conducting a regional applicability analysis of these soil moisture products is essential as a preliminary step for their effective utilization. The triple collocation (TC) method enables the estimation of the standard deviation of errors in products when true soil moisture values are unavailable. It assesses data uncertainty and mitigates the influence of product errors on fusion, thereby enhancing product accuracy significantly. In this study, the TC uncertainty error analysis was employed to integrate Soil Moisture Active Passive (SMAP), the Advanced Microwave Scanning Radiometer 2 (AMSR-2), and the European Space Agency Climate Change Initiative (ESA CCI) active (ESA CCI A) and passive (ESA CCI P) products, with ground-based measurements serving as a reference. Traditional evaluation metrics, such as the correlation coefficient (R), bias, root mean square error (RMSE), and unin situed root mean square error (ubRMSE), were employed to evaluate the accuracy of the product. The findings indicate that SMAP and ESA CCI P products demonstrate strong spatiotemporal continuity within the research area and exhibit low uncertainty across various land types. The products derived from the Advanced Microwave Scanning Radiometer 2 (AMSR-2) exhibit a high level of temporal and spatial continuity; however, there is a requirement for enhancing their accuracy. The products of ESA CCI A exhibit notable spatiotemporal disjunction, contributing significantly to their elevated level of uncertainty. After fusion with TC analysis, the correlation coefficient (R = 0.7) of the TC-2 product derived from the fusion of SMAP, AMSR-2, and ESA CCI P products is significantly higher than the correlation coefficient of the TC-1 product (R = 0.65) obtained from the fusion of SMAP, AMSR-2, and ESA CCI A products at a 95% confidence level. The integration of data can efficiently mitigate the challenges associated with spatiotemporal gaps and inaccuracies in products, offering a dependable foundation for the subsequent utilization of remote sensing products.

Ephemeral gully (EG) erosion is an important type of water erosion. Understanding the spatial distribution of EGs and other influencing factors at a regional scale is crucial for developing effective soil and water management strategies. Unfortunately, this area has not been sufficiently studied. The present study visually interpreted the EGs based on Google Earth images in 137 small watersheds uniformly distributed in the Loess Plateau, compared them with measured results, and analyzed the factors influencing EG formation and density using GeoDetector. The results showed that visually interpreting EGs from Google Earth images was suitable for EG regional studies. Out of the 137 small watersheds, 33.6% had EG occurrence with an average density of 3.41 km/km2. Rainfall (R) and slope gradient (S) were the primary factors influencing the formation of EGs, while the area proportion of sloping farmland (APSF) and soil erodibility (K) were the main factors affecting EG density. The interaction of dual factors had a greater influence compared to single factors, with the interaction between S and Normalized Difference Vegetation Index (NDVI) having the greatest impact on EG formation and the interaction between K and NDVI on EG density. Although natural forces significantly influence whether EGs can form in a specific area, human activities greatly affect the density of the gullies that develop. This underscores the importance of proper land management in controlling gully erosion. These findings could provide theoretical support for EG prediction models and a scientific basis for soil and water loss control strategies at the regional scale.

Introduction Whether and when to monitor the amount of anti-factor Xa (aFXa) activity in critically ill patients with complex diseases to prevent venous thromboembolism (VTE) remain unclear. This study is a randomised controlled trial to investigate the effect of aFXa level monitoring on reducing VTE and to establish a new method for accurately preventing VTE in critically ill patients with low-molecular-weight heparin (LMWH).Methods and analysis A randomised controlled trial is planned in two centres with a planned sample size of 858 participants. Participants will be randomly assigned to three groups receiving LMWH prophylaxis at a 1:1:1 ratio: in group A, peak aFXa levels will serve as the guide for the LMWH dose; in group B, the trough aFXa levels will serve as the guide for the LMWH dose; and in group C, participants serving as the control group will receive a fixed dose of LMWH. The peak and trough aFXa levels will be monitored after LMWH (enoxaparin, 40 mg, once daily) reaches a steady state for at least 3 days. The monitoring range for group A’s aFXa peak value will be 0.3–0.5 IU/mL, between 0.1 and 0.2 IU/mL is the target range for group B’s aFXa trough value. In order to reach the peak or trough aFXa levels, groups A and B will be modified in accordance with the monitoring peak and trough aFXa level. The incidence of VTE will serve as the study’s primary outcome indicator. An analysis using the intention-to-treat and per-protocol criterion will serve as the main outcome measurement.Ethics and dissemination The Xuanwu Hospital Ethics Committee of Capital Medical University and Peking University First Hospital Ethics Committee have approved this investigation. It will be released in all available worldwide, open-access, peer-reviewed publications.Trial registration number NCT05382481

Geoparks are home to unique and precious geological sites and have a rich historical and cultural heritage. Most studies have focused on their tourism value and/or educational significance. However, far too little attention has been paid to the impact of geopark construction on the local ecological environment. The Xiangxi UNESCO Global Geopark (XXGG) was used as a case study to explore the impact of global geopark construction on local ecological quality. Three ecological indices, including an ecological quality index based on productive, residential, and ecological land use, an improved remote-sensing ecological index (RSEI-2), and net primary productivity (NPP), were adopted to evaluate the ecological quality of XXGG during two periods: before construction (from 2015 to 2017) and during construction of XXGG (from 2018 to 2020). The results show that: (1) in general, all ecological quality indicators showed a downtrend (from 2015 to 2017) followed by an uptrend (from 2018 to 2020), indicating that construction and development of XXGG has had a significant positive effect on local ecological quality. This occurred because a series of environmental protection measures were taken after application to the United Nations Educational, Scientific, and Cultural Organization (UNESCO) Global Geoparks (UGGPs) for membership at the end of 2017. (2) The areas of XXGG with excellent and improved ecological quality are mainly distributed in the northern and southeastern portions, which are located in the protected area with high coverage rates of forest and other vegetation. Poor ecological quality in the east and south is closely related with human activities, such as ethnic tourism development. The results explore the relationship between regional construction of the geopark and ecological effects and provide a scientific reference for sustainable development of global geoparks.

Abstract Background Lysine acetyltransferase 6B (KAT6B) encodes a highly conserved histone acetyltransferase that regulates the expression of multiple genes and is essential for human growth and development. Methods We identified a novel frameshift variant c.3185del (p.leu1062Argfs*52) in a 5‐year‐old Chinese boy and further analyzed KAT6B expression and its interacting complexes and downstream products using real‐time quantitative polymerase chain reaction (qPCR). Furthermore, we assessed its three‐dimensional protein structure and compared the variant with other reported KAT6B variants. Results The deletion changed the leucine at position 1062 into an arginine, resulting in translation termination after base 3340, which may have affected protein stability and protein–protein interactions. KAT6B mRNA expression levels in this case were substantially different from those of the parents and controls in the same age range. There were also significant differences in mRNA expression levels among affected children's parents. RUNX2 and NR5A1, downstream products of the gene, affect the corresponding clinical symptoms. The mRNA expression levels of the two in children were lower than those of their parents and controls in the same age range. Conclusion This deletion in KAT6B may affect protein function and cause corresponding clinical symptoms through interactions with key complexes and downstream products.

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a global public health problem. Lifestyle modifications aimed at promoting weight loss and weight maintenance remain the current first‐line treatments for NAFLD. Objective We aim to identify barriers and enabling factors in weight management among patients with NAFLD using the capability, opportunity, motivation, behaviour (COM‐B) model of behaviour. Design This study adopted a qualitative design using semistructured interviews analysed with content analysis and the COM‐B framework. Setting and Participants Interviews were conducted with 27 patients with NAFLD who experienced successful or unsuccessful weight reduction. Results Our study included 27 participants: 15 participants with successful weight loss (successful weight loss refers to a decrease in body weight ≥7% of the initial body weight for patients with NAFLD) and 12 participants with unsuccessful weight loss. Thirty‐five themes (19 barriers and 16 facilitators) were mapped onto the COM‐B model as barriers and facilitators to weight management among patients with NAFLD. The key barriers were lack of time and energy, lack of awareness of weight, lack of attention to NAFLD, treating food as a reward or compensation and social entertainment. The key facilitators were having basic weight loss knowledge and skills, strong motivation, attention to NAFLD, unsuccessful weight loss experiences and positive feedback from phased success. Conclusion In addition to identifying factors consistent with existing studies, this study identified factors that influence weight management in NAFLD patients, such as basic weight loss skills and rational thinking before weight loss, which were not previously reported. This has clinical implications for clinical healthcare providers and health management services for the improvement of education and support regarding lifestyle improvement and weight management in patients with NAFLD. Patient or Public Contribution We recruited potential participants from the Bariatric Clinic, Hepatology Clinic and Physical Examination Center of hospitals between March 2021 and October 2021. Twenty‐seven patients with NAFLD who had successful or unsuccessful weight loss experiences participated in the study and responded to questions on weight management.

A large number of studies have shown that propolis has positive effects in the treatment of type 2 diabetes mellitus (T2DM). However, there are have only been a few reports that are based on an ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) analysis of the fecal metabolomics of ethanol extract of propolis (EEP) in the treatment of T2DM. The present investigation was designed to screen potential biomarkers of T2DM by the metabonomic method and to explain the possible anti-diabetes mechanism of EEP according to the changes in the biomarkers. The results showed that EEP improved the body weight (BW) of T2DM mice, lowered blood sugar levels, and significantly restored blood biochemical indicators related to T2DM, such as fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), aspartate transaminase (AST), and alanine aminotransferase (ALT). Liver pathology showed that EEP reversed liver damage caused by T2DM. Metabolomics data identified 27 potential biomarkers in fecal samples. EEP effectively regulated the dysfunction in the metabolic pathways of glycerophospholipids, sphingolipids, riboflavins, and sterol lipids caused by T2DM. In summary, our research results revealed positive effects of EEP in the treatment of T2DM and provided potential candidate markers for further research and in the clinical treatment of T2DM.

Abstract Background Research on the relationship between disclosure of HIV status to male sexual partners (HIV disclosure) and quality of life (QOL) revealed complex and even contradictory results. The impact of HIV disclosure on various domains of QOL and the mediation effect between them are unclear. The purposes of this study were to explore the impact of HIV disclosure on QOL among men who have sex with men (MSM), and whether HIV treatment self-efficacy mediated these relationships. Methods The data came from a baseline survey on the design of a randomized control trial conducted in Shandong, China. A total of 579 MSM patients were included. SPSS 24.0 was used to conduct independent samples t test, one-way analysis of variance and nonparametric tests and the PROCESS macro was used to conduct mediation analysis. Results Among 579 participants, 16.06% disclosed their HIV infection status to their male sexual partners. The effect of HIV disclosure on QOL was mediated by treatment self-efficacy. Self-efficacy played partial mediating role in social relationships, meaning that HIV disclosure had both direct and indirect effects on this factor. In the overall QOL and domains of physical, psychological, independence, and environment, HIV disclosure had an indirect effect only through self-efficacy and no significant effect on the spirituality domain. Conclusions The results emphasize the importance of HIV disclosure and self-efficacy on the QOL of MSM patients and suggest that health care providers should assist MSM patients in deciding whether to disclose their HIV status during daily medical services.

Abstract Background Consistent and complete adherence is considered an essential requirement for patients on antiretroviral therapy (ART). This study aimed to evaluate the impact of ART duration on ART adherence, identify the trend of complete adherence, and compare the factors associated with ART adherence between short-term and long-term ART group among men who have sex with men (MSM) living with HIV in Jinan of China. Methods MSM living with HIV aged 18 or above and currently on ART were recruited from October to December 2020 using convenience sampling. Univariate and multivariable logistic regressions were used to evaluate the impact of ART duration on adherence and compare factors associated with ART adherence between subgroups. The Mann–Kendall test was used to identify the trend of complete adherence. Results A total of 585 participants were included in analysis, consisting of 352 on short-term ART (ART initiation ≤ 3 years) and 233 on long-term ART (ART initiation > 3 years). Significant difference of complete ART adherence between short-term and long-term ART group was detected (79.8% vs. 69.1%, P = 0.003). Multivariable analysis showed that men with longer ART duration were less likely to report complete ART adherence (AOR = 0.88, 95% CI 0.81–0.95). A descending trend of complete adherence was identified (Z = 1.787, P = 0.037). Alcohol use and lack of medication reminders were barriers to complete adherence for both of the subgroups. Conclusions Sustained efforts to encourage maintaining adherence for a lifetime are necessary, especially for those on long-term ART. Future interventions should be tailored to subgroups with different ART duration and individuals with specific characteristics.

Abstract Background Research on myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease (MOGAD) among Chinese children is relatively rare. Therefore, this study aimed to explore and analyze the clinical characteristics and prognoses of Chinese children with acquired demyelinating syndromes (ADSs) who tested positive or negative for MOG-Ab. Methods The clinical data of children with MOGAD who were treated in the Department of Neurology at Shanghai Children's Hospital from January 2017 to October 2021 were retrospectively collected. Results Among 90 children with ADSs, 30 were MOG-Ab-positive, and 60 were MOG-Ab-negative. MOG-Ab-positive children experienced more prodromal infections than did MOG-Ab-negative children (P

Abstract Background Sepsis still remains a major challenge in intensive care medicine with unacceptably high mortality among patients with septic shock. Due to current limitations of human CD19+CD24hiCD38hi Breg cells (Bregs) studies among sepsis, here, we tried to evaluate Bregs in severity and prognostic value in patients with sepsis. Methods Peripheral blood from 58 patients with sepsis and 22 healthy controls was analyzed using flow cytometry to evaluate the frequency and number of Bregs. All cases were divided into non-survived or survived group after 28 days followed up. Spearman's correlation analysis was performed on Bregs frequency and clinical indices. The area under the curve was acquired using the receiver operating characteristic analysis to assess the sensitivity and specificity of Bregs for outcome of sepsis. Survival curve analysis and binary logistic regression were applied to estimate the value of Bregs in prognosis among cases with sepsis. Results Sepsis patients had decreased proportions and number of Bregs. Sepsis patients with low frequency of Bregs were associated with an increased risk of septic shock. Bregs frequency is inversely associated with lactate, SOFA, and APACHE II and positively correlated with Tregs frequency. Low levels of Bregs closely correlated with septic outcomes. Numbers of Bregs were prediction factors for poor prognosis. Conclusions Frequency and number of Bregs decreased, and Bregs deficiency revealed poor prognosis in patients with sepsis.

Abstract Background Antiretroviral therapy (ART) adherence is still suboptimal among some key populations, highlighting the need for innovative tailored strategies. This randomized controlled trial (RCT) aimed to evaluate the effect of a differentiated digital intervention on ART adherence among men who have sex with men (MSM) living with HIV in China. Methods The two-armed parallel RCT was conducted at one HIV clinic in Jinan of China from October 19, 2020, to June 31, 2021. Men were referred by health providers to join the study and then choose one of three digital strategies—text message, only instant message, or instant message plus social media. They were assigned in a 1:1 ratio to the intervention arm or control arm using block randomization, and inside each arm, there were three groups depending on the type of delivering the message. The groups were divided according to participants’ preferred digital strategies. The intervention arm received ART medication messages, medication reminders, peer education, and involved in online discussion. The control arm received messages on health behavior and nutrition. The primary outcome was self-reported optimal ART adherence, defined as not missing any doses and not having any delayed doses within a one-month period. Secondary outcomes included CD4 T cell counts, viral suppression, HIV treatment adherence self-efficacy, and quality of life. Intention-to-treat analysis with generalized linear mixed models was used to evaluate the intervention’s effect. Results A total of 576 participants were enrolled, including 288 participants assigned in the intervention arm and 288 assigned in the control arm. Most were ≤ 40 years old (79.9%) and initiated ART ≤ 3 years (60.4%). After intervention, the proportion of participants achieving optimal ART adherence in the intervention arm was higher than in the control arm (82.9% vs 71.1%). The differentiated digital intervention significantly improved ART adherence (RR = 1.74, 95%CI 1.21–2.50). Subgroup analysis showed one-to-one instant message-based intervention significantly improved ART adherence (RR = 2.40, 95% CI 1.39–4.17). Conclusions The differentiated digital intervention improved ART adherence among MSM living with HIV in China, which could be integrated into people living with HIV (PLWH) management and further promoted in areas where PLWH can access text messaging and instant messaging services. Trial registration ChiCTR2000041282. Retrospectively registered on 23 December 2020.

Abstract Background Pro-opiomelanocortin (POMC) neurons play a sexually dimorphic role in body weight and glucose balance. However, the mechanisms for the sex differences in POMC neuron functions are not fully understood. Results We detected small conductance calcium-activated potassium (SK) current in POMC neurons. Secondary analysis of published single-cell RNA-Seq data showed that POMC neurons abundantly express SK3, one SK channel subunit. To test whether SK3 in POMC neurons regulates POMC neuron functions on energy and glucose homeostasis, we used a Cre-loxP strategy to delete SK3 specifically from mature POMC neurons. POMC-specific deletion of SK3 did not affect body weight in either male or female mice. Interestingly, male mutant mice showed not only decreased food intake but also decreased physical activity, resulting in unchanged body weight. Further, POMC-specific SK3 deficiency impaired glucose balance specifically in female mice but not in male mice. Finally, no sex differences were detected in the expression of SK3 and SK current in total POMC neurons. However, we found higher SK current but lower SK3 positive neuron population in male POMC neurons co-expressing estrogen receptor α (ERα) compared to that in females. Conclusion These results revealed a sexually dimorphic role of SK3 in POMC neurons in both energy and glucose homeostasis independent of body weight control, which was associated with the sex difference of SK current in a subpopulation of POMC + ERα + neurons.

Abstract Background Avian coccidiosis is an important parasitic disease that has serious adverse effects on the global poultry industry. The extensive use of anticoccidial drugs has resulted in an increase in drug resistance. Ethanamizuril (EZL) is a novel triazine with high anticoccidial activity. Methods We compared oocyst production and sporulation between EZL-sensitive (S) and EZL-resistant Eimeria tenella strains (R10 and R200) and used label-free quantitative proteomics to identify differentially expressed proteins (DEPs) between these strains. Results We generated two EZL-resistant E. tenella strains: strain R10, which was induced using a constant dose of 10 mg EZL/kg poultry feed, and strain R200, which was generated by gradually increasing the EZL dosage to 200 mg EZL/kg poultry feed. With an increase in resistance, the total oocyst output decreased, but the percentage of sporulation did not change significantly. We identified a total of 7511 peptides and 1282 proteins, and found 152 DEPs in the R10 strain versus the S strain, 426 DEPs in the R200 strain versus the S strain and 494 DEPs in the R200 strain versus the R10 strain. When compared with the S strain, 86 DEPs were found to have consistent trends in both resistant strains. The DEPs were primarily involved in ATP and GTP binding, invasion, and membrane components. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the DEPs suggested that they are involved in transcription and translation processes. Protein–protein interaction network analysis of the 86 DEPs showed that 10 proteins were hubs in the functional interaction network (≥ 8 edges) and five of them were ribosomal proteins. Conclusions The results of the present study indicate that the resistance mechanisms of E. tenella against EZL might be related to the transcriptional and translational processes, especially in the factors that inhibit the growth of parasites. The DEPs found in this study provide new insights into the resistance mechanisms of E. tenella against EZL. Further research on these potential targets holds promise for new chemotherapeutic approaches for controlling E. tenella infections. Graphical Abstract

Abstract Background Hypertension, a well-known risk factor, contributes to millions of deaths from cardiovascular and renal diseases worldwide. However, evidence on the association between frequency of dairy product consumption and hypertension is inconsistent. Methods The data for the present study are from the Tongxiang baseline dataset of the China Kadoorie Biobank prospective study. A total of 53,916 participants aged 30–79 years were included in the final analysis. Multivariable logistic regression was utilized to evaluate the association of dairy product consumption with hypertension, and multiple linear regression was conducted to assess the association of dairy product consumption with systolic and diastolic blood pressure. Results Of the 53,916 participants, 2.6% reported consuming dairy products weekly, and 44.4% had prevalent hypertension. After adjusting for socio-demographic status, lifestyle factors, BMI, waist circumference, sleep duration and snoring, when compared with participants who never consumed dairy products, the odds ratios (95% CI) for hypertension among those consuming dairy products less than once per week, and ≥ 1 time per week were 0.85 (0.77–0.95) and 0.74 (0.65–0.84), respectively. The corresponding odds ratios (95% CI) for men were 0.85 (0.71–1.02) and 0.75 (0.61–0.92), respectively (P trend = 0.001), and for women were 0.88 (0.76–1.01) and 0.77 (0.65–0.91), respectively. (P trend

Osteoporosis (OP) is characterized by a decrease in osteoblasts and an increase in adipocytes in the bone marrow compartment, alongside abnormal bone/fat differentiation, which ultimately results in imbalanced bone homeostasis. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into osteoblasts and adipocytes to maintain bone homeostasis. Several studies have shown that lncRNAs are competitive endogenous RNAs that form a lncRNA–miRNA network by targeting miRNA for the regulation of bone/fat differentiation in BMSCs; this mechanism is closely related to the corresponding treatment of OP and is important in the development of novel OP-targeted therapies. However, by reviewing the current literature, it became clear that there are limited summaries discussing the effects of the lncRNA–miRNA network on osteogenic/adipogenic differentiation in BMSCs. Therefore, this article provides a review of the current literature to explore the impact of the lncRNA–miRNA network on the osteogenic/adipogenic differentiation of BMSCs, with the aim of providing a new theoretical basis for the treatment of OP.

Glucose is the basic fuel essential for maintenance of viability and functionality of all cells. However, some neurons — namely, glucose-inhibited (GI) neurons — paradoxically increase their firing activity in low-glucose conditions and decrease that activity in high-glucose conditions. The ionic mechanisms mediating electric responses of GI neurons to glucose fluctuations remain unclear. Here, we showed that currents mediated by the anoctamin 4 (Ano4) channel are only detected in GI neurons in the ventromedial hypothalamic nucleus (VMH) and are functionally required for their activation in response to low glucose. Genetic disruption of the Ano4 gene in VMH neurons reduced blood glucose and impaired counterregulatory responses during hypoglycemia in mice. Activation of VMHAno4 neurons increased food intake and blood glucose, while chronic inhibition of VMHAno4 neurons ameliorated hyperglycemia in a type 1 diabetic mouse model. Finally, we showed that VMHAno4 neurons represent a unique orexigenic VMH population and transmit a positive valence, while stimulation of neurons that do not express Ano4 in the VMH (VMHnon-Ano4) suppress feeding and transmit a negative valence. Together, our results indicate that the Ano4 channel and VMHAno4 neurons are potential therapeutic targets for human diseases with abnormal feeding behavior or glucose imbalance.

ABSTRACT The gut flora is a treasure house of diverse bacteriophages maintaining a harmonious and coexistent relationship with their hosts. The giant panda (Ailuropoda melanoleuca), as a vulnerable endemic species in China, has existed for millions of years and is regarded as a flagship species for biodiversity conservation. And yet, limited studies have analyzed the phage communities in the gut of giant pandas. Using viral metagenomic analysis, the phageomes of giant pandas and other relative species were investigated. Our study explored and compared the composition of phage communities from different animal sources. Giant pandas possessed more diverse and abundant phage communities in the gut compared with other relevant animals. Phylogenetic analyses based on the phage terminase large subunit (TerL) showed that the Caudovirales phages in giant pandas also presented highly genetic diversity. Our study revealed the diversity of phage communities in giant pandas and other relative species, contributing to the health maintenance of giant pandas and laying the groundwork for molecular evolution research of bacteriophages in mammals. IMPORTANCE Gut phageome plays an important role in shaping gut microbiomes by direct interactions with bacteria or indirect influences on the host immune system, potentially regulating host health and disease status. The giant panda (Ailuropoda melanoleuca) is a vulnerable and umbrella species for biodiversity conservation. Our work explored and compared the gut phageome of giant pandas and relative species, contributing to the health maintenance of giant pandas.

Clouds and cloud shadow cover cause missing data in some images captured by the Gaofen-1 Wide Field of View (GF-1 WFV) cameras, limiting the extraction and analysis of the image information and further applications. Therefore, this study proposes a methodology to fill GF-1 WFV images using the spatial autocorrelation and improved weighting (SAIW) method. Specifically, the search window size is adaptively determined using Getis-Ord Gi* as a metric. The spatial and spectral weights of the pixels are computed using the Chebyshev distance and spectral angle mapper to better filter the suitable similar pixels. Each missing pixel is predicted using linear regression with similar pixels on the reference image and the corresponding similar pixel located in the non-missing region of the cloudy image. Simulation experiments showed that the average correlation coefficient of the proposed method in this study is 0.966 in heterogeneous areas, 0.983 in homogeneous farmland, and 0.948 in complex urban areas. It suggests that SAIW can reduce the spread of errors in the gap-filling process to significantly improve the accuracy of the filling results and can produce satisfactory qualitative and quantitative fill results in a wide range of typical land cover types and has extensive application potential.

The purpose of this study is to explore the possibility of using graphene–zinc oxide–hydroxyapatite (GO/ZnO/nHAp) composite microspheres as bone regeneration materials by making use of the complementary advantages of nanocomposites, so as to provide reference for the clinical application of preventing and solving bacterial infection after implantation of synthetic materials. Firstly, GO/ZnO composites and hydroxyapatite nanoparticles were synthesized using the hydrothermal method, and then GO/ZnO/nHAp composite microspheres were prepared via high-temperature sintering. The graphene–zinc oxide–calcium phosphate composite microspheres were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), energy dispersion spectroscopy (EDS), water contact angle measurement, degradation and pH determination, and differential thermal analysis (DiamondTG/DTA). The biocompatibility, osteogenic activity, and antibacterial activity of GO/ZnO/nHAp composite microspheres were further studied. The results of the cell experiment and antibacterial experiment showed that 0.5% and 1% GO-ZnO-nHAp composite microspheres not only had good biocompatibility and osteogenic ability but also inhibited Escherichia coli and Staphylococcus aureus by more than 45% and 70%. Therefore, GO/ZnO/nHAp composite microspheres have good physical and chemical properties and show good osteogenic induction and antibacterial activity, and this material has the possibility of being used as a bone regeneration material.