Explore the vast range of titles available.

While strategies such as chemotherapy and immunotherapy have become the first-line standard therapies for patients with advanced or metastatic cancer, acquired resistance is still inevitable in most cases. The introduction of antibody‒drug conjugates (ADCs) provides a novel alternative. ADCs are a new class of anticancer drugs comprising the coupling of antitumor mAbs with cytotoxic drugs. Compared with chemotherapeutic drugs, ADCs have the advantages of good tolerance, accurate target recognition, and small effects on noncancerous cells. ADCs occupy an increasingly important position in the therapeutic field. Currently, there are 13 Food and Drug Administration (FDA)‒approved ADCs and more than 100 ADC drugs at different stages of clinical trials. This review briefly describes the efficacy and safety of FDA-approved ADCs, and discusses the related problems and challenges to provide a reference for clinical work.

Satellite sensors are one of the most important means of collecting real-time geospatial information. Due to their characteristics such as large spatial coverage and strong capability for dynamic monitoring, they are widely used in the observation of real-time flood situation information for flood situational awareness and response. Selecting the optimum sensor is vital when multiple sensors exist. Presently, sensor selection predominantly hinges on human experience and various quantitative and qualitative evaluation methods. Yet, these methods lack optimization considering the flood’s spatiotemporal characteristics, such as different flood phases and geographical environmental factors. Consequently, they may inaccurately evaluate and select the inappropriate sensor. To address this issue, an innovative observation capability evaluation model (OCEM) is proposed to quantitatively pre-evaluate the performance of flood-water-observation-oriented satellite sensors. The OCEM selects and formulates various flood-water-observation-related capability factors and supports dynamic weight assignment considering the spatiotemporal characteristics of the flood event. An experiment involving three consecutive flood phase observation tasks was conducted. The results demonstrated the flexibility and effectiveness of the OCEM in pre-evaluating the observation capability of various satellite sensors across those tasks, accounting for the spatiotemporal characteristics of different flood phases. Additionally, qualitative and quantitative comparisons with related methods further affirmed the superiority of the OCEM. In general, the OCEM has provided a “measuring table” to optimize the selection and planning of sensors in flood management departments for acquiring real-time flood information.

This research investigated enhancing the efficiency of enzymatic hydrolysis of wheat straw via freeze–thaw pretreatment and assessed the physicochemical structural changes after this pretreatment. The enzymatic hydrolysis efficiency of cellulose and hemicellulose was enhanced, and hemicellulose was more susceptible to pretreatment. The highest enzymatic hydrolysis efficiency of cellulose and hemicellulose was 57.06 and 70.66%, respectively, at − 80 ℃ for 24 h and − 10 ℃ for 24 h, respectively, which were 2.23 and 3.13-fold higher than the control levels, respectively. Scanning electron microscopy images indicated that transverse cracks appeared before longitudinal cracks with stronger pretreatment conditions, and holes were found in every sample after this pretreatment. Fourier transform infrared spectroscopy and X-ray diffraction analysis indicated that freeze–thaw pretreatment affected both the crystalline and amorphous regions and disrupted the hydrogen bonds within them. This study provides a physical pretreatment method to improve the efficiency of enzymatic hydrolysis of wheat straw.

Pulmonary hypertension (PH) is a progressive cardiopulmonary disorder. It features elevated pulmonary arterial pressure, which leads to right ventricular failure and increased mortality. PH’s insidious nature, with no specific clinical symptoms, hinders early diagnosis. Recent investigations have implicated vascular cell senescence in the pathogenesis of PH; however, the identification of early diagnostic biomarkers and the development of senescence-targeted therapeutics remain areas of unmet need.In this study, an integrative transcriptomic analysis of multiple datasets was undertaken to delineate differentially expressed senescence-related genes (DESRGs). Feature genes were selected via the implementation of LASSO regression, random forest, and support vector machine algorithms. Subsequently, a diagnostic nomogram was constructed, predicated on six hub genes. The discriminative capacity of the nomogram was rigorously validated utilizing external datasets. Single-gene gene set enrichment analysis (GSEA) was executed to elucidate potential biological functions. The expression profiles of core genes were corroborated through single-cell RNA sequencing and qPCR in an in vitro hypoxia model of pulmonary artery smooth muscle cells. Finally, connectivity map (cMAP) analysis and molecular docking were employed to identify potential therapeutic small molecules.The analysis identified 20 DESRGs. Six feature genes (LCN2, CBS, ABCB1, NQO1, TWIST1, TLR8) were consistently selected by all three machine learning methods. The diagnostic nomogram exhibited an area under the curve (AUC) of 0.974 in the training cohort and demonstrated robust performance in independent validation cohorts. Notably, CBS, TLR8, and NQO1 were significantly downregulated in validation datasets, single-cell sequencing, and the in vitro hypoxia model. GSEA revealed significant enrichment of innate immune responses, the IL-17 pathway, and oxidative stress. cMAP analysis identified TUL-XXI039 as a potential therapeutic compound, with molecular docking studies predicting strong binding affinities (binding energies < -8.0 kcal/mol) to CBS, TLR8, and NQO1.This study introduces a novel, high-precision diagnostic model for PH based on senescence-related genes, underscoring CBS, TLR8, and NQO1 as promising biomarker candidates. TUL-XXI039 emerges as a potential multi-target therapeutic candidate for PH, thus meriting further investigation.

Farmed mink are frequently exposed to circulating influenza A viruses (IAVs), as confirmed by viral isolation and serological evidence. Previous work reveals that naïve mink serve as susceptible hosts for both avian and human influenza strains, highlighting their potential role in influenza ecology. In this study, we investigated whether farmed mink naturally pre-exposed to H9 retain the capacity to serve as “mixing vessels” for reassorting human and avian IAVs. Our results demonstrate that they remain fully susceptible and permissive to infection by both avian H6N6 and human H1N1 influenza strains. Notably, efficient transmission of these viruses occurred among farmed mink, confirming their potential to sustain viral exchange. These findings indicate that farmed mink represent highly permissive hosts capable of facilitating reassortment between circulating human and avian IAVs. Given this risk, current mink farming practices may substantially increase the likelihood of a pandemic emergence. We therefore urge immediate revision, stringent enhancement, and rigorous enforcement of biosecurity protocols and active surveillance systems in fur farming operations.

Hongbing Shen and colleagues report a genome-wide association study for lung cancer in individuals of Han Chinese ancestry. The authors identify two new lung cancer susceptibility loci. Lung cancer is the leading cause of cancer-related deaths worldwide. To identify genetic factors that modify the risk of lung cancer in individuals of Chinese ancestry, we performed a genome-wide association scan in 5,408 subjects (2,331 individuals with lung cancer (cases) and 3,077 controls) followed by a two-stage validation among 12,722 subjects (6,313 cases and 6,409 controls). The combined analyses identified six well-replicated SNPs with independent effects and significant lung cancer associations ( P < 5.0 × 10 −8 ) located in TP63 (rs4488809 at 3q28, P = 7.2 × 10 −26 ), TERT - CLPTM1L (rs465498 and rs2736100 at 5p15.33, P = 1.2 × 10 −20 and P = 1.0 × 10 −27 , respectively), MIPEP - TNFRSF19 (rs753955 at 13q12.12, P = 1.5 × 10 −12 ) and MTMR3 - HORMAD2 - LIF (rs17728461 and rs36600 at 22q12.2, P = 1.1 × 10 −11 and P = 6.2 × 10 −13 , respectively). Two of these loci (13q12.12 and 22q12.2) were newly identified in the Chinese population. These results suggest that genetic variants in 3q28, 5p15.33, 13q12.12 and 22q12.2 may contribute to the susceptibility of lung cancer in Han Chinese.

Glycosylation and phosphorylation as the commonest and most important posttranslational modifications of proteins play critical roles in biological processes. Specific and sensitive strategies have been developed to identify the glycosylation and phosphorylation of proteins by mass spectrometry but most of these methods have mainly focused on enriching glycopeptides or phosphopeptides separately, and few of them can enrich both of them. In this work, highly selective SiO 2 –NH 2 @TiO 2 hollow microspheres were designed and synthesized for the simultaneous selective enrichment of both phosphopeptides and glycopeptides. Because of the bifunctionalized property of the titanium dioxide and the amino group, the hollow microspheres were successfully applied for the simultaneous enrichment of phosphopeptides and glycopeptides. We evaluated the enrichment selectivity of the SiO 2 –NH 2 @TiO 2 hollow microspheres by capturing phosphopeptides and glycopeptides from a peptide mixture of bovine β-casein, horseradish peroxidase, and bovine serum albumin in a molar ratio of 1:1:500 (1.7 × 10 −12 mol β-casein and horseradish peroxidase, 8.5 × 10 −10 mol bovine serum albumin in 100 μL). Graphical Abstract Workflow of the simultaneous enrichment strategy for phosphopeptides and glycopeptides by SiO 2 –NH 2 @TiO 2 hollow microspheres

At present, there are few reports about the proteomics changes provoked by butylated hydroxytoluene (BHT) supplementation on cryopreserved semen in mammals. Thus, we aimed to evaluate the effects of different concentrations of BHT on goat sperm and to investigate the proteomics changes of adding BHT to cryopreserved goat ( Capra hircus ) sperm. Firstly, semen samples were collected from four goats, and frozen in the basic extenders containing different concentrations of BHT (0.5 mM, 1.0 mM, 2.0 mM) and a control without BHT, respectively. After thawing, the protective effects of dose-dependent replenished BHT to the freezing medium on post-thaw sperm motility, integrities of plasma membrane and acrosome, reactive oxygen species levels were confirmed, with 0.5 mM BHT being the best (B group) as compared to the control (without BHT, C group). Afterwards, TMT-based quantitative proteomic technique was performed to profile proteome of the goat sperm between C group and B group. Parallel reaction monitoring was used to confirm reliability of the data. Overall, 2,476 proteins were identified and quantified via this approach. Comparing the C and B groups directly (C vs . B), there were 17 differentially abundant proteins (DAPs) po-tentially associated with sperm characteristics and functions were identified, wherein three were upregulated and 14 were downregulated, respectively. GO annotation analysis demonstrated the potential involvement of the identified DAPs in metabolic process, multi-organism process, reproduction, reproductive process, and cellular process. KEGG enrichment analysis further indicated their potential roles in renin-angiotensin system and glutathione metabolism pathways. Together, this novel study clearly shows that BHT can effectively improve quality parameters and fertility potential of post-thawed goat sperm at the optimal concentration, and its cryoprotection may be realized through regulation of sperm metabolism and antioxidative capability from the perspective of sperm proteomic modification.

Scientific and reasonable application of potassium fertilizer is an important agronomic measure to achieve high yield and high quality of sweetpotato, and it is of great significance to determine the appropriate amount of potassium fertilizer in the field. For this we constructing a model of the critical K dilution curve (CKDC) of sweetpotato under different N levels to determine crop nutritional statuses. In this study, a 3-year field experiment was conducted in Zhejiang Province in China, using two nitrogen levels (N0: 0 kg ha −1 and N1: 120 kg ha −1 ) and five K fertilization rates (K0: 0, K1: 75, K2: 150, K3: 225, K4: 300 kg ha −1 ) for two sweetpotato cultivars of ‘Shang 19’ and ‘Yan 25’. Plant dry matter first increased and then decreased and the K concentration increased continuously with an increase in K application rate. The required amount of K fertilizer to achieve maximum sweetpotato yield under high N conditions was greater than that under low nitrogen conditions. A new CKDC based on dry matter and K concentration was created to assess K nutrition in sweetpotato. At two N levels, CKDC was expressed by the negative power function equation, aboveground: K c(N0) = 5.30W -0.463 , R 2  = 0.79, and K c(N1) = 4.23W -0.298 , R 2  = 0.78, under-ground: K c(N0) = 1.38W -0.125 , R 2  = 0.81, and K c(N1) = 1.32W -0.132 , R 2  = 0.72;whole-plant: K c(N0) = 4.31W -0.421 , R 2  = 0.80; Kc (N1) = 3.89W -0.415 , R 2  = 0.79. There is no significantly different for CKDC of whole-plant and underground between N0 and N1 levels, while there is significantly different for CKDC of aboveground between N0 and N1 levels. N fertilizer can strengthen the dilution effect of K concentration, and its effect on the aboveground is greater than that on the underground and whole-plant. Then, potassium nutrition indexes were constructed to identify K nutrition status and could be used as a reliable indicator for K nutrition diagnosis of sweetpotato. The results provide a theoretical basis to improve K fertilization management and sustainability of sweetpotato.

We examined how stress affects the work ability of an aging workforce, how health mediates this relationship, and how the effects of stress on work ability differ in relation to social status. We analyzed data from the Health and Retirement Survey, namely, 2921 observations in 2010, 2289 observations in 2012, and 2276 observations in 2014. Ongoing chronic stress, social status, health status, and associations with individual work ability were assessed with ordinary least squares regression. Stress was significantly inversely associated with work ability. Health may function as a mediator between individual stress and work ability. The effects of stress and health on work ability decreased as social status increased. To cope with the challenges of aging workforces, future policy-makers should consider job resources and social status.