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Abstract Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV1] to forced vital capacity ratio

Abstract Nipah virus (NiV) is a zoonotic emergent paramyxovirus that can cause severe encephalitis and respiratory infections in humans, with a high fatality rate ranging from 40% to 75%. Currently, there are no approved human vaccines or antiviral drugs against NiV. Here, we designed a ferritin-based self-assembling nanoparticle displaying the NiV G head domain on the surface (NiV G-ferritin) and assessed immune responses elicited by the soluble NiV G head domain (NiV sG) or NiV G-ferritin. Immunization with NiV G-ferritin or NiV sG conferred complete protection against lethal NiV challenge without detection of viral RNA in Syrian golden hamsters. Compared to NiV sG, NiV G-ferritin induced significantly faster, broader, and higher serum neutralizing responses against three pathogenic henipaviruses (NiV-Malaysia, NiV-Bangladesh, and Hendra virus). Moreover, NiV G-ferritin induced a durable neutralizing immunity in mice as antisera potently inhibited NiV infection even after six months of the third immunization. Additionally, we isolated a panel of 27 NiV G-binding monoclonal antibodies (mAbs) from NiV G-ferritin immunized mice and found that these mAbs targeted four distinct antigenic sites on NiV G head domain with two sites that have not been defined previously. Notably, 25 isolated mAbs have potent neutralizing activity with 50% inhibitory concentrations less than 10 ng/mL against NiV pseudovirus. Collectively, these findings provide new insights into the immunogenicity of NiV G protein and reveal that NiV G-ferritin is a safe and highly effective vaccine candidate against Nipah virus infection.

Abstract Tin-lead halide perovskites with a bandgap near 1.2 electron-volt hold great promise for thin-film photovoltaics. However, the film quality of solution-processed Sn-Pb perovskites is compromised by the asynchronous crystallization behavior between Sn and Pb components, where the crystallization of Sn-based perovskites tends to occur faster than that of Pb. Here we show that the rapid crystallization of Sn is rooted in its stereochemically active lone pair, which impedes coordination between the metal ion and Lewis base ligands in the perovskite precursor. From this perspective, we introduce a noncovalent binding agent targeting the open metal site of coordinatively unsaturated Sn(II) solvates, thereby synchronizing crystallization kinetics and homogenizing Sn-Pb alloying. The resultant single-junction Sn-Pb perovskite solar cells achieve a certified power conversion efficiency of 24.13 per cent. The encapsulated device retains 90 per cent of the initial efficiency after 795 h of maximum power point operation under simulated one-sun illumination.

Abstract Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging bunyavirus that causes severe viral hemorrhagic fever and thrombocytopenia syndrome with a fatality rate of up to 30%. No licensed vaccines or therapeutics are currently available for humans. Here, we develop seven monoclonal antibodies (mAbs) against SFTSV surface glycoprotein Gn. Mechanistic studies show that three neutralizing mAbs (S2A5, S1G3, and S1H7) block multiple steps during SFTSV infection, including viral attachment and membrane fusion, whereas another neutralizing mAb (B1G11) primarily inhibits the viral attachment step. Epitope binning and X-ray crystallographic analyses reveal four distinct antigenic sites on Gn, three of which have not previously been reported, corresponding to domain I, domain II, and spanning domain I and domain II. One of the most potent neutralizing mAbs, S2A5, binds to a conserved epitope on Gn domain I and broadly neutralizes infection of six SFTSV strains corresponding to genotypes A to F. A single dose treatment of S2A5 affords both pre- and post-exposure protection of mice against lethal SFTSV challenge without apparent weight loss. Our results support the importance of glycoprotein Gn for eliciting a robust humoral response and pave a path for developing prophylactic and therapeutic antibodies against SFTSV infection.

Relationships with parents and teachers are crucial to a child's socialization. However, little is known about the transactional processes between parent-child and teachers-student relationships and their mediating mechanisms. This short-term longitudinal study examined bidirectional relations between positive parent-child and teachers-student relationships, and the potential mediating role of positivity within these relations. There were 3,450 Chinese children (44.8% girls; M[subscript age] = 10.93 years) who participated in a four-wave longitudinal study, spaced 6 months apart. The random intercept cross-lagged panel modeling found: (a) both father-child and mother-child relationships directly predicted teachers-student relationships, and vice versa; (b) positivity functioned as a mediator in bidirectional relations between parent-child and teachers-student relationships. These results support a transactional spillover effect between parent-child and teachers-student relationships, suggesting Chinese children may become caught in a virtuous cycle either directly or indirectly via their positivity.

Background Comorbidity between non-suicidal self-injury (NSSI) and depression and anxiety was common. In the framework of network theory, the examination of directionality and gender differences in longitudinal relationships at the symptom level made a significant contribution to the understanding of comorbidity. Therefore, this study employed cross-lagged panel network analysis to investigate the longitudinal interrelations between NSSI and depression and anxiety in Chinese adolescents, with a focus on gender differences. Method The study was conducted with a sample of 884 senior high school students (F/M: 481/403; mean age: 15.19 ± 0.48 years) from Jinchang City, Gansu Province, China. All respondents completed the Adolescent Non-Suicidal Self-Injury Assessment Questionnaire and the two subscales (depression and anxiety) of the Brief Symptom Inventory at two intervals. The data were estimated in R 4.2.0 to construct the cross-lagged panel network (CLPN). Results The CLPN results uncovered the gender differences. For boys, self-hitting and feeling scared emerged as central symptoms. Cutting predicted subsequent feelings of sadness (β = − 0.57), tension (β = − 0.52) and indifference (β = − 0.49), potentially serving as a bridge connecting NSSI to depression and anxiety. For girls, biting themselves and feeling scared were central symptoms. Carving and skin rubbing predicted subsequent feelings of indifference (β = − 0.31, −0.21), bridging NSSI to depression and anxiety. In addition, feeling scared emerged as the key bridge symptom connecting depression and anxiety. Conclusion The findings showed the gender-specific developmental characteristics of the directional relations between NSSI and depression and anxiety at the symptom level. They provided new insights into the comorbidity of NSSI and depression and anxiety, carrying important implications for the screening and intervention of adolescent NSSI.

Background Emerging evidence suggests a central role for inflammation in cardiac conduction disorder (CCD). It is unknown whether habitual physical activity could modulate the inflammation‐associated risks of incident CCD in the general population. Methods and Results This population‐based cohort was derived from the China Kailuan study, including a total of 97 192 participants without prior CCD. The end points included incident CCD and its subcategories (atrioventricular block and bundle‐branch block). Systemic inflammation was indicated by the monocyte‐to‐lymphocyte ratio (MLR). Over a median 10.91‐year follow‐up, 3747 cases of CCD occurred, with 1062 cases of atrioventricular block and 2697 cases of bundle‐branch block. An overall linear dose‐dependent relationship was observed between MLR and each study end point (all P‐nonlinearity≥0.05). Both higher MLR and physical inactivity were significantly associated with higher risks of conduction block. The MLR‐associated risks of developing study end points were higher in the physically inactive individuals than in those being physically active, with significant interactions between MLR levels and physical activity for developing CCD (P‐interaction=0.07) and bundle‐branch block (P‐interaction

AimThis study aimed to develop a marital self-disclosure programme to alleviate the fear of cancer recurrence in patients with gastric cancer who are undergoing chemotherapy.DesignDelphi method.MethodsData from available literature and stakeholder interviews were utilised to formulate the initial draft of a marital self-disclosure programme aimed to alleviate the fear of cancer recurring in patients with gastric cancer and undergoing chemotherapy. A panel of experts subsequently conducted a two-round modified Delphi method to finalise the programme.ResultsA total of 13 experts participated in the first round of consultation, while 11 experts were involved in the second round, as two experts withdrew due to unavailability. The response rates of both rounds of expert consultation were 100 and 84.62%, respectively, and the expert authority coefficients (Cr) of the programme were 0.83 and 0.84, respectively. The coordination coefficients of the expert opinions were 0.124 (χ2 = 61.214, p = 0.010) and 0.167 (χ2 = 69.668, p = 0.001) for each Delphi round. The average score of the second round was (4.545 ± 0.688) to (5.000 ± 0), with a full score ratio of 0.55–1.00. The coefficient of variation (CV) ranged from 0 to 0.031. Outcomes from both rounds of consultations were considered acceptable and credible. The finalised marital self-disclosure programme for alleviating the fear of cancer recurrence in patients with gastric cancer undergoing chemotherapy consists of two parts; disclosure guidance for patients and their spouse with nine items, and the structure and themes of marital self-disclosure with 31 items.Patient or public contributionAfter two rounds of expert consultations, the marital self-disclosure programme for patients with gastric cancer undergoing chemotherapy is suggested to be scientifically valid and reliable. This programme is anticipated to potentially support patients and their spouses effectively by providing a reliable intervention plan focused on alleviating the fear of cancer recurrence.

Alzheimer’s disease (Alzheimer’s disease, AD) is a progressive neurological disorder characterized by memory loss and cognitive impairment. It is characterized by the formation of tau protein neurofibrillary tangles and β-amyloid plaques. Recent studies have found that mitochondria in neuronal cells of AD patients exhibit various dysfunctions, including reduced numbers, ultrastructural changes, reduced enzyme activity, and abnormal kinetics. These abnormal mitochondria not only lead to the loss of normal neuronal cell function, but are also a major driver of AD progression. In this review, we will focus on the advances of mitochondria and their multi-omics in AD research, with particular emphasis on how mitochondrial dysfunction in AD drives disease progression. At the same time, we will focus on summarizing how mitochondrial genomics technologies have revealed specific details of these dysfunctions and how therapeutic strategies targeting mitochondria may provide new directions for future AD treatments. By delving into the key mechanisms of mitochondria in AD related to energy metabolism, altered kinetics, regulation of cell death, and dysregulation of calcium-ion homeostasis, and how mitochondrial multi-omics technologies can be utilized to provide us with a better understanding of these processes. In the future, mitochondria-centered therapeutic strategies will be a key idea in the treatment of AD.

Diabetic retinopathy is the major cause of blindness in diabetic patients, with limited treatment options that do not always restore optimal vision. Retinal nerve degeneration and vascular degeneration are two primary pathological processes of diabetic retinopathy. The retinal nervous system and vascular cells have a close coupling relationship. The connection between neurodegeneration and vascular degeneration is not yet fully understood. Recent studies have found that microRNA plays a role in regulating diabetic retinal neurovascular degeneration and can help delay the progression of the disease. This article will review how microRNA acts as a bridge connecting diabetic retinal neurodegeneration and vascular degeneration, focusing on the mechanisms of apoptosis, oxidative stress, inflammation, and endothelial factors. The aim is to identify valuable targets for new research and clinical treatment of diabetic retinopathy.

BackgroundThis study aimed to explore the knowledge and attitude (KA) toward postoperative antithrombotic management and prevention among coronary artery disease (CAD) patients who underwent coronary revascularization.MethodsThis cross-sectional study enrolled CAD outpatients and inpatients between May and December 2023 at Kailuan Medical Group at Tangshan. Basic demographic characteristics and KA scores were collected through a self-made questionnaire.ResultsThis study included 523 valid questionnaires. The mean knowledge and attitude scores were 13.20 ± 6.20 (range: 0–26) and 43.68 ± 6.01 (range: 21–50), respectively, indicating poor knowledge and favorable attitude. Multivariable logistic regression analysis showed that junior high school education (OR = 2.160, P = 0.035), high school or technical school education (OR = 2.356, P = 0.039), and monthly average income >5,000 RMB (OR = 3.407, P = 0.002) were independently associated with knowledge. Knowledge (OR = 1.095, P = 0.002), BMI ≥ 24.0 kg/m2 (OR = 0.372, P = 0.011), junior high school (OR = 3.699, P = 0.002), high school or technical school (OR = 2.903, P = 0.028), high associate degree or above education (OR = 6.068, P = 0.014), monthly average income 3,000–5,000 RMB (OR = 0.296, P = 0.005), monthly average income > 5,000 RMB (OR = 0.225, P = 0.021), with hypertension (OR = 0.333, P = 0.003), blood tests every 2–3 weeks (OR = 10.811, P = 0.011), blood tests every month (OR = 4.221, P = 0.024), and blood tests every 2–3 months (OR = 3.342, P = 0.033) were independently associated with attitude.ConclusionCAD patients who underwent coronary revascularization had poor knowledge but favorable attitudes toward postoperative antithrombotic management and prevention. The study underscores the need for targeted education, especially for individuals with lower education and income levels, ultimately improving patient compliance and cardiovascular outcomes.

Chlorella contains a variety of polysaccharides with complex composition and structure, which are composed of various monosaccharides such as galactose, rhamnose, glucose, arabinose, mannose, xylose and glucuronic acid. The glycosidic linkages of polysaccharides are diverse, including α-1,6-glucose, β-1,3-galactose, α-1,6-galactose, α-1,3-rhamnose, α-1,2-rhamnose, α-1,5-arabinose, α-1,6-mannose and β-1,4-xylose. Some polysaccharides are modified by methylation, sulfation and acetylation. Meanwhile, many studies have shown that polysaccharides have multiple functions such as immunoregulatory, anti-inflammatory, antioxidant, anti-tumor, antibacterial and intestinal flora-regulatory effects. At present, monosaccharide composition analysis, methylation combined with gas chromatography-mass spectrometry (GC-MS) and two-dimensional nuclear magnetic resonance (2D-NMR) spectroscopy are mainly used for research on the structure of chlorella polysaccharides such as analysis of monosaccharide composition, glycosidic bond types, branch chain substitution positions and branch chain types. This review hopes to provide valuable information for the fine structural analysis and structure-activity relationship study of polysaccharides from Chlorella.

BackgroundPatients with gastric cancer experience different degrees of fear of cancer recurrence. The fear of cancer recurrence can cause and worsen many physical and psychological problems. We considered the “intimacy and relationship processes in couples’ psychosocial adaptation” model. ObjectiveThe study aims to examine the effectiveness of a marital self-disclosure intervention for improving the level of fear of cancer recurrence and the dyadic coping ability among gastric cancer survivors and their spouses. MethodsThis is a quasiexperimental study with a nonequivalent (pretest-posttest) control group design. The study will be conducted at 2 tertiary hospitals in Taizhou City, Jiangsu Province, China. A total of 42 patients with gastric cancer undergoing chemotherapy and their spouses will be recruited from each hospital. Participants from Jingjiang People’s Hospital will be assigned to an experimental group, while participants from Taizhou People’s Hospital will be assigned to a control group. The participants in the experimental group will be involved in 4 phases of the marital self-disclosure (different topics, face-to-face) intervention. Patients will be evaluated at baseline after a diagnosis of gastric cancer and reassessed 2 to 4 months after baseline. The primary outcome is the score of the Fear of Progression Questionnaire-Short Form (FoP-Q-SF) for patients. The secondary outcomes are the scores of the FoP-Q-SF for partners and the Dyadic Coping Inventory. ResultsResearch activities began in October 2022. Participant enrollment and data collection began in February 2023 and are expected to be completed in 12 months. The primary results of this study are anticipated to be announced in June 2024. ConclusionsThis study aims to assess a marital self-disclosure intervention for improving the fear of cancer recurrence in Chinese patients with gastric cancer and their spouses. The study is likely to yield desirable positive outcomes as marital self-disclosure is formulated based on evidence and inputs obtained through stakeholder interviews and expert consultation. The study process will be carried out by nurses who have received psychological training, and the quality of the intervention will be strictly controlled. Trial RegistrationClinicalTrials.gov NCT05606549; https://clinicaltrials.gov/study/NCT05606549 International Registered Report Identifier (IRRID)DERR1-10.2196/55102

With the global population growth and increasing demand for high-quality protein, aquaculture has experienced rapid development. Fish culture management and feed supply are crucial components of aquaculture. Traditional baiting management relies on experiential judgment and regular observation, which often leads to inefficient baiting practices and wastage. To address these issues, intelligent bait casting decisions have emerged. Leveraging advanced artificial intelligence algorithms, intelligent bait casting decisions can overcome most drawbacks of traditional bait management and enhance breeding efficiency. However, most of the current intelligent baiting decisions are focused on using methods such as image processing and target detection to identify different feeding actions and patterns. These methods do not discuss based on video streams and do not consider the changes in fish behavior during the baiting process. Therefore, we proposed a real-time analysis method based on the density distribution of fish feeding behavior (FishFeed). Firstly, this method upgrades the input mechanism, not only handling static images but also capable of real-time video stream analysis. Secondly, by evaluating the fish school density distribution through a new intelligent baiting strategy, this method can monitor the feeding behavior of fish school during the baiting process in real time. Finally, we constructed a dataset for fish school density analysis (DlouFishDensity) that includes a wealth of video and image frames, providing a valuable resource for research. Experimental results indicate that our algorithm outperforms MCNN, improving MAE by 1.63 and 1.35, MSE by 1.92 and 1.58, and reducing prediction time by 2.56 seconds on the same dataset. By implementing real-time analysis of fish feeding behavior density distribution, our method offers a more efficient and effective approach to baiting management in aquaculture, contributing to improved breeding efficiency and resource utilization.

Background/purpose: Gingival phenotype (GP) has been reported to influence the treatment planning and clinical outcomes in several dental specialties. This study aimed to investigate optimal cutoff values for gingival thickness (GT) measurement at different landmarks to determine GP. The correlations between GT and bone thickness (BT) of buccal alveolar crest were also analyzed. Materials and methods: A total of 600 teeth were included. GP was clinically determined by the transparency of a periodontal probe through the gingival margin (TRAN). Measurements for free gingival thickness (GT1), cementoenamel junction gingival thickness (GT2), supracrestal gingival thickness (GT3), subcrestal 1 mm gingival thickness (GT4) and BT at 1, 3 mm apical from the alveolar crest edge (BT1 and BT2) were assessed on cone-beam computed tomography (CBCT) images. Spearman's correlation coefficient was used to evaluate correlations between GT and BT. Results: The optimal cutoff values of GT using CBCT method to discriminate GP were 0.75 mm for GT1, 0.85 mm for GT2, 1.15 mm for GT3 and 0.45 mm for GT4. There was significantly positive correlation between GT and BT at all levels (r: 0.375–0.903). The correlations between GT3 and BT (r: 0.789–0.903) were strong, while correlations between GT4 and BT were weak (r: 0.375–0.467). Conclusion: The optimal cutoff values of gingival thickness using CBCT method to discriminate gingival phenotype at each gingival landmark were determined. The supracrestal gingival thickness might be an indicator of buccal alveolar crest bone thickness, which could provide valuable perspectives on clinical diagnosis, treatment planning and decision-making.

Abstract Coronavirus disease 2019 (COVID-19) was first reported three years ago, when a group of individuals were infected with the original SARS-CoV-2 strain, based on which vaccines were developed. Here, we develop six human monoclonal antibodies (mAbs) from two elite convalescents in Wuhan and show that these mAbs recognize diverse epitopes on the receptor binding domain (RBD) and can inhibit the infection of SARS-CoV-2 original strain and variants of concern (VOCs) to varying degrees, including Omicron strains XBB and XBB.1.5. Of these mAbs, the two most broadly and potently neutralizing mAbs (7B3 and 14B1) exhibit prophylactic activity against SARS-CoV-2 WT infection and therapeutic effects against SARS-CoV-2 Delta variant challenge in K18-hACE2 KI mice. Furthermore, post-exposure treatment with 7B3 protects mice from lethal Omicron variants infection. Cryo-EM analysis of the spike trimer complexed with 14B1 or 7B3 reveals that these two mAbs bind partially overlapped epitopes onto the RBD of the spike, and sterically disrupt the binding of human angiotensin-converting enzyme 2 (hACE2) to RBD. Our results suggest that mAbs with broadly neutralizing activity against different SARS-CoV-2 variants are present in COVID-19 convalescents infected by the ancestral SARS-CoV-2 strain, indicating that people can benefit from former infections or vaccines despite the extensive immune escape of SARS-CoV-2.

Abstract The rapid spread of monkeypox in multiple countries has resulted in a global public health threat and has caused international concerns since May 2022. Poxvirus encoded M2 protein is a member of the poxvirus immune evasion family and plays roles in host immunomodulation via the regulation of innate immune response mediated by the NF-κB pathway and adaptive immune response mediated by B7 ligands. However, the interaction of monkeypox virus (MPXV) M2 with B7 ligands and structural insight into poxviral M2 function have remained elusive. Here we reveal that MPXV M2, co-existing as a hexamer and a heptamer, recognizes human B7.1 and B7.2 (hB7.1/2) with high avidities. The binding of oligomeric MPXV M2 interrupts the interactions of hB7.1/2 with CD28 and CTLA4 and subverts T cell activation mediated by B7.1/2 costimulatory signals. Cryo-EM structures of M2 in complex with hB7.1/2 show that M2 binds to the shallow concave face of hB7.1/2 and displays sterically competition with CD28 and CTLA4 for the binding to hB7.1/2. Our findings provide structural mechanisms of poxviral M2 function and immune evasion deployed by poxviruses.

Abstract Obesity and metabolic syndromes are becoming increasingly prevalent worldwide. Insulin resistance (IR) is a common complication of obesity. However, IR occurrence varies across individuals with obesity and may involve epigenetic factors. To rationalize the allocation of healthcare resources, biomarkers for the early risk stratification of individuals with obesity should be identified. MicroRNAs (miRNAs) are closely associated with metabolic diseases and involved in epigenetic regulation. In this review, we have summarized the changes in miRNA expression in the peripheral circulation and tissues of patients and animals with obesity-associated IR over the last 5 years and identified several candidate biomarkers that predict obesity-related IR. There are areas for improvement in existing studies. First, more than the predictive validity of a single biomarker is required, and a biomarker panel needs to be formed. Second, miRNAs are often studied in isolation and do not form a network of signaling pathways. We believe that early biomarkers can help clinicians accurately predict individuals prone to obesity-related IR at an early stage. Epigenetic regulation may be one of the underlying causes of different clinical outcomes in individuals with obesity. Future studies should focus on objectively reflecting the differences in miRNA profile expression in individuals with obesity-related IR, which may help identify more reliable biomarkers. Understanding the metabolic pathways of these miRNAs can help design new metabolic risk prevention and management strategies, and support the development of drugs to treat obesity and metabolic disorders.

Osteonecrosis of the femoral head (ONFH) is a refractory orthopedic condition characterized by bone cell ischemia, necrosis, bone trabecular fracture, and clinical symptoms such as pain, femoral head collapse, and joint dysfunction that can lead to disability. The disability rate of ONFH is very high, which imposes a significant economic burden on both families and society. Steroid-associated osteonecrosis of the femoral head (SANFH) is the most common type of ONFH. However, the pathogenesis of SANFH remains unclear, and it is an urgent challenge for orthopedic surgeons to explore it. In this paper, the pathogenesis of SANFH and its related signaling pathways were briefly reviewed to enhance comprehension of the pathogenesis and prevention of SANFH.

Recovering valuable active substances from the by-products of agricultural processing is a crucial concern for scientific researchers. This paper focuses on the enrichment of soybean trypsin inhibitor (STI) from soybean whey wastewater using either ammonium sulfate salting or ethanol precipitation, and discusses their physicochemical properties. The results show that at a 60% ethanol content, the yield of STI was 3.983 mg/mL, whereas the yield was 3.833 mg/mL at 60% ammonium sulfate saturation. The inhibitory activity of STI obtained by ammonium sulfate salting out (A-STI) was higher than that obtained by ethanol precipitation (E-STI). A-STI exhibited better solubility than E-STI at specific temperatures and pH levels, as confirmed by turbidity and surface hydrophobicity measurements. Thermal characterization revealed that both A-STI and E-STI showed thermal transition temperatures above 90 °C. Scanning electron microscopy demonstrated that A-STI had a smooth surface with fewer pores, while E-STI had a rough surface with more pores. In conclusion, there was no significant difference in the yield of A-STI and E-STI (p < 0.05); however, the physicochemical properties of A-STI were superior to those of E-STI, making it more suitable for further processing and utilization. This study provides a theoretical reference for the enrichment of STI from soybean whey wastewater.