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This study provides detailed description of a newly-discovered Callicarpa yongshunensis Wen B. Xu, Xiao D. Li & Yan Ling Liu (Lamiaceae) species from Hunan, China. The species shares similarities in the inflorescence, glandular colour and leaf shape features with C. luteopunctata H. T. Chang and C. giraldii Hesse ex Rehd., while its white fruits are similar to those of C. longifolia Lamk. However, its procumbent, evergreen shrub and white fruits are distinctly different from those of C. luteopunctata and C. giraldii, while its procumbent, scarless nodes and stellate pubescence free fruits distinguishes it from C. longifolia. Images, distribution, morphological features, molecular phylogenetic classification and conservation assessment of this new Callicarpa species are explored.

Abstract Chronic rhinosinusitis (CRS) can be traditionally classified as CRSwNP [with nasal polyps (NPs)] and CRSsNP (without NPs) based on the clinical phenotypes but recently suggested to be classified by the endotypes. We have identified overexpression of the cyclooxygenase-2 (COX-2) gene in NP tissues of Taiwanese CRSwNP patients. Therefore, in this study, we sought to investigate its protein expression/location/distribution in NP specimens and explore its roles in nasal polyposis. The COX-2 protein and mRNA expression was found higher in NPs than that in the control and CRSsNP patients’ nasal tissues, mainly located at the epithelium and subepithelial stroma. Consistently, the CRS-related peptidoglycan (PGN) and bradykinin provoked COX-2 mRNA and protein upregulation in the human NP-derived fibroblasts and caused PGE2, thromboxane A2 (TXA2), and interleukin (IL-6) secretion in culture medium. Further analysis revealed that the PI3K/Akt activation and COX-2 induction were necessarily required for PGN-induced IL-6 production/secretion and the induced PGE2, but not TXA2, was speculated to affect IL-6 protein trafficking and production. Finally, the IL-6 increase observed in vitro could also be detected in NP tissues. Collectively, we demonstrated here that COX-2 protein and IL-6 are overexpressed in human NP tissues. In response to PGN challenge, the PI3K/Akt activation and COX-2-mediated PGE2 autacoid correlates with extracellular IL-6 protein trafficking/production in NP-derived fibroblasts, which can additionally contribute to the production of Th17-related cytokines such as IL-17 and TNF-α. This study also suggests COX-2 as a special biomarker for CRSwNP endotyping and may highlight the importance of COX-2 inhibitors in treating CRSwNP.

Objective This meta-analysis aims to refine the understanding of the optimal choice between different cage shapes in transforaminal lumbar interbody fusion (TLIF) by systematically comparing perioperative data, radiological outcomes, clinical results, and complications associated with banana-shaped and straight bullet cages. Methods A meticulous literature search encompassing PubMed, Embase, Scopus, Web of Science, China Knowledge Network, and Wanfang Data was executed up to October 5, 2023. Inclusion criteria focused on studies comparing banana-shaped and straight bullet cages in TLIF. The quality of included studies was assessed using appropriate tools such as the Newcastle-Ottawa Scale (NOS) for nonrandomized studies. Rigorous evaluations were performed for radiographic outcomes, including disc height (DH), segmental lordosis (SL), lumbar lordosis (LL), subsidence, and fusion rates. Clinical outcomes were meticulously evaluated using visual analogue scale (VAS), Oswestry Disability Index (ODI), and complications. Results The analysis incorporated 7 studies, involving 573 patients (297 with banana-shaped cages, 276 with straight cages), all with NOS ratings exceeding 5 stars. No statistically significant differences were observed in operative time, blood loss, or hospitalization between the 2 cage shapes. Banana-shaped cages exhibited greater changes in DH (p = 0.001), SL (p = 0.02), and LL (p = 0.01). Despite statistically higher changes in ODI for straight cages (26.33, p < 0.0001), the actual value remained similar to banana-shaped cages (26.15). Both cage types demonstrated similar efficacy in VAS, complication rates, subsidence, and fusion rates. Conclusion Although banana-shaped cages can excel in restoring DH, SL, and LL, straight bullet cages can provide comparable functional improvements, pain relief, and complication rates.

Chronic pancreatitis (CP) is a multifaceted disorder influenced by environmental and genetic factors, with smoking and alcohol consumption being major contributors. Recent developments encompass the advent of innovative transgenic models and the identification of susceptibility genes, shedding light on the genetic aspect of CP. The pathogenesis of this disease involves a complex interplay of pancreatic acinar cell dysfunction, inflammatory reactions, and fibrosis. Current research delves into understanding these molecular mechanisms. Pain, a pivotal symptom of CP, has been increasingly studied to develop effective therapeutic interventions. Diagnostic advancements, including endoscopic ultrasound, radiomics, and blood-based markers, have shown potential in enhancing early CP detection. Moreover, recent clinical trials have optimized treatment approaches, such as pancreatic stone fragmentation, stent placement, and decision-making between endoscopic and surgical procedures. Emerging therapies, including chemical pancreatectomy and gene therapy, present promising opportunities for improved CP management.

ABSTRACTThe gravitational curvatures (GC, the third-order derivatives of the gravitational potential) in gravity field modeling are gaining increased interest in geosciences. The crustal effects of the GC and Moho variation sensed by the GC are not fully evaluated for the current study. In this contribution, the effects of the GC induced by topographic and anomalous crustal masses are investigated based on ETOPO1 and CRUST1.0 models using the tesseroids. By adopting the gravitational stripping correction, the residual GC sensed by the CRUST1.0 Moho depths are presented globally to examine whether the GC can sense crustal mass anomalies at the satellite altitude of 260 km . The spatial analysis using the Pearson correlations coefficient (PCC) between the residual GC and the CRUST1.0 Moho depths is performed. Among the 10 residual GC functionals, the PCC value of the residual radial-radial-radial component [Formula: see text] is largest with 0.31, where this value is highly dependent on the spectral content removed from the EGM2008, e.g. signals assumed to relate to deeper mass anomalies. Numerical experiments show that with the increased order of the derivatives up to third-order, the fineness level of different global Moho sensed crustal mass anomalies increases correspondingly. Taking the Tibetan plateau for example, the values of the [Formula: see text] can better reveal the detailed features of the Tibetan plateau’s Moho depth than these of the lower-order residual radial functionals (i.e. disturbing potential [Formula: see text], disturbing radial gravity vector [Formula: see text], and disturbing radial-radial gravity gradient tensor [Formula: see text]), especially for the Qaidam, Sichuan, Tarim, and Turpan basins. Numerical results over the Himalayan region demonstrate that the GC component [Formula: see text] has some potential in geophysical inversion. These residual GC functionals would help to get a better knowledge of the internal structures of the Earth and other planetary objects.

Abstract Classical swine fever virus (CSFV) and porcine circovirus type 2 (PCV2) are two of the most devastating and economically significant pathogens affecting pig populations worldwide. Administration of a combination of vaccines against swine pathogens has been demonstrated to be as efficacious as the administration of single vaccines. In this study, we developed and tested a novel bivalent subunit vaccine against CSFV and PCV2. The safety and efficacy of this vaccine were demonstrated in mice and specific pathogen-free (SPF) piglets. In addition to investigating the serological responses after immunization, challenge studies with both viruses were also conducted. The results showed that this CSFV/PCV2 bivalent vaccine elicited a high level of neutralizing antibodies against both viruses and provided protection in challenge studies. In conclusion, the CSFV/PCV2 bivalent vaccine is safe and effective against CSFV or PCV2 challenge.

Abstract Senescence of vascular smooth muscle cells (VSMCs) contributes to aging-related cardiovascular diseases by promoting arterial remodelling and stiffness. Ferroptosis is a novel type of regulated cell death associated with lipid oxidation. Here, we show that pro-ferroptosis signaling drives VSMCs senescence to accelerate vascular NAD+ loss, remodelling and aging. Pro-ferroptotic signaling is triggered in senescent VSMCs and arteries of aged mice. Furthermore, the activation of pro-ferroptotic signaling in VSMCs not only induces NAD+ loss and senescence but also promotes the release of a pro-senescent secretome. Pharmacological or genetic inhibition of pro-ferroptosis signaling, ameliorates VSMCs senescence, reduces vascular stiffness and retards the progression of abdominal aortic aneurysm in mice. Mechanistically, we revealed that inhibition of pro-ferroptotic signaling facilitates the nuclear-cytoplasmic shuttling of proliferator-activated receptor-γ and, thereby impeding nuclear receptor coactivator 4-ferrtin complex-centric ferritinophagy. Finally, the activated pro-ferroptotic signaling correlates with arterial stiffness in a human proof-of-concept study. These findings have significant implications for future therapeutic strategies aiming to eliminate vascular ferroptosis in senescence- or aging-associated cardiovascular diseases.

Abstract Background Single-nucleotide variants (SNVs) within gene coding sequences can significantly impact pre-mRNA splicing, bearing profound implications for pathogenic mechanisms and precision medicine. In this study, we aim to harness the well-established full-length gene splicing assay (FLGSA) in conjunction with SpliceAI to prospectively interpret the splicing effects of all potential coding SNVs within the four-exon SPINK1 gene, a gene associated with chronic pancreatitis. Results Our study began with a retrospective analysis of 27 SPINK1 coding SNVs previously assessed using FLGSA, proceeded with a prospective analysis of 35 new FLGSA-tested SPINK1 coding SNVs, followed by data extrapolation, and ended with further validation. In total, we analyzed 67 SPINK1 coding SNVs, which account for 9.3% of the 720 possible coding SNVs. Among these 67 FLGSA-analyzed SNVs, 12 were found to impact splicing. Through detailed comparison of FLGSA results and SpliceAI predictions, we inferred that the remaining 653 untested coding SNVs in the SPINK1 gene are unlikely to significantly affect splicing. Of the 12 splice-altering events, nine produced both normally spliced and aberrantly spliced transcripts, while the remaining three only generated aberrantly spliced transcripts. These splice-impacting SNVs were found solely in exons 1 and 2, notably at the first and/or last coding nucleotides of these exons. Among the 12 splice-altering events, 11 were missense variants (2.17% of 506 potential missense variants), and one was synonymous (0.61% of 164 potential synonymous variants). Notably, adjusting the SpliceAI cut-off to 0.30 instead of the conventional 0.20 would improve specificity without reducing sensitivity. Conclusions By integrating FLGSA with SpliceAI, we have determined that less than 2% (1.67%) of all possible coding SNVs in SPINK1 significantly influence splicing outcomes. Our findings emphasize the critical importance of conducting splicing analysis within the broader genomic sequence context of the study gene and highlight the inherent uncertainties associated with intermediate SpliceAI scores (0.20 to 0.80). This study contributes to the field by being the first to prospectively interpret all potential coding SNVs in a disease-associated gene with a high degree of accuracy, representing a meaningful attempt at shifting from retrospective to prospective variant analysis in the era of exome and genome sequencing.

Hydrangea xinfeniae W.B.Ju & J.Ru, a new species of Hydrangeaceae from Sichuan Province, China, is described and illustrated. The new species belongs to Hydrangea sect. Dichroa (Lour.) Y.De Smet & Samain, with its distinctive characteristic being the nearly superior ovary. It shares morphological similarities with H. yaoshanensis (Y.C.Wu) Y.De Smet & C.Granados, but can be distinguished by its hirsute trichomes densely covered on the branchlets, leaves, peduncles and pedicels, broadly elliptic to rectangular-elliptic leaf blade with nearly rounded base, coarse teeth leaf margins, 3–4 pairs of lateral veins, corymbose cyme with few and loose branches, lanceolate bract, the calyx tube and lobes margin with sparsely hirsute trichomes, adaxially glabrous and abaxially sparsely hirsute petal, outer whorl filaments are linear, inner ones are awl-shaped, glabrous styles, and the nearly superior ovary. H. xinfeniae sp. nov. currently known from only three relatively small populations of the type locality, and its conservation status is assessed as Data Deficient (DD).

Mechanical interlocking is a prominent phenomenon both in macroscopic objects and in microscopic molecules. Not only is it aesthetically appealing, it also leads to unique properties such as extraordinary mechanical stability. This review focuses on mechanically interlocked biomacromolecules. After a brief clarification on the concept and scope, we discuss their classification and summarize the three main types of mechanically interlocked biomacromolecules (i.e., DNA, RNA, and proteins) in terms of their natural occurrence, synthetic methods, relevant applications, and functional benefits. It has been found that mechanical interlocking reshapes the conformational space of these chain molecules, which provides numerous opportunities to tailor their properties and create new functions. Since the development of ''assembly-reaction'' synergies has greatly facilitated their synthetic availability, these mechanically linked biomacromolecules will become unique and promising candidates for various applications in biomaterials and biomedicine.

Background Cardiac aging represents an independent risk factor for aging‐associated cardiovascular diseases. Although evidence suggests an association between NOD‐, LRR‐, and pyrin domain–containing protein 3 (NLRP3) inflammasome formation and numerous cardiovascular diseases, its role in cardiac aging remains largely unclear. Methods and Results The longevity of mice with wild‐type and NLRP3 knockout (NLRP3−/−) genotypes was assessed, with or without d‐galactose treatment. Cardiac function was evaluated using echocardiography, and cardiac histopathology was examined through hematoxylin and eosin and Masson's trichrome staining. Senescence‐associated β‐galactosidase (SA‐β‐gal) staining was employed to detect cardiac aging. Western blotting was used to assess aging‐related proteins (p53, p21) and pyroptosis‐related proteins. Additionally, dihydroethidium staining, lactate dehydrogenase release, and interleukin‐1β ELISA assays were performed, along with measurements of total superoxide dismutase and malondialdehyde levels. In vitro, H9c2 cells were exposed to d‐galactose for 24 hours in the absence or presence of N‐acetyl‐l‐cysteine (reactive oxygen species inhibitor), BAY‐117082 (nuclear factor κ‐light‐chain enhancer of activated B cells inhibitor), MCC950 (NLRP3 inhibitor), and VX‐765 (Caspase‐1 inhibitor). Immunofluorescence staining was employed to detect p53, gasdermin D, and apoptosis‐associated speck‐like protein proteins. Intracellular reactive oxygen species levels were assessed using fluorescence microscopy and flow cytometry. Senescence‐associated β‐galactosidase staining and Western blotting were also employed in vitro for the same purpose. The results showed that NLRP3 upregulation was implicated in aging and cardiovascular diseases. Inhibition of NLRP3 extended life span, mitigated the aging phenotype, improved cardiac function and blood pressure, ameliorated lipid metabolism abnormalities, inhibited pyroptosis in cardiomyocytes, and ultimately alleviated cardiac aging. In vitro, the inhibition of reactive oxygen species, nuclear factor κ‐light‐chain enhancer of activated B cells, NLRP3, or caspase‐1 attenuated NLRP3 inflammasome‐mediated pyroptosis. Conclusions The reactive oxygen species/nuclear factor κ‐light‐chain enhancer of activated B cells/NLRP3 signaling pathway loop contributes to d‐galactose–treated cardiomyocyte senescence and cardiac aging.

Timely and precise detection of emerging infections is imperative for effective outbreak management and disease control. Human mobility significantly influences the spatial transmission dynamics of infectious diseases. Spatial sampling, integrating the spatial structure of the target, holds promise as an approach for testing allocation in detecting infections, and leveraging information on individuals’ movement and contact behavior can enhance targeting precision. This study introduces a spatial sampling framework informed by spatiotemporal analysis of human mobility data, aiming to optimize the allocation of testing resources for detecting emerging infections. Mobility patterns, derived from clustering point-of-interest and travel data, are integrated into four spatial sampling approaches at the community level. We evaluate the proposed mobility-based spatial sampling by analyzing both actual and simulated outbreaks, considering scenarios of transmissibility, intervention timing, and population density in cities. Results indicate that leveraging inter-community movement data and initial case locations, the proposed Case Flow Intensity (CFI) and Case Transmission Intensity (CTI)-informed spatial sampling enhances community-level testing efficiency by reducing the number of individuals screened while maintaining a high accuracy rate in infection identification. Furthermore, the prompt application of CFI and CTI within cities is crucial for effective detection, especially in highly contagious infections within densely populated areas. With the widespread use of human mobility data for infectious disease responses, the proposed theoretical framework extends spatiotemporal data analysis of mobility patterns into spatial sampling, providing a cost-effective solution to optimize testing resource deployment for containing emerging infectious diseases.

ABSTRACT Background The aim was to identify the nutritional indexes, construct a prognostic model, and develop a nomogram for predicting individual survival probability in pan‐cancers. Methods Nutritional indicators, clinicopathological characteristics, and previous major treatment details of the patients were collected. The enrolled patients were randomly divided into training and validation cohorts. Least absolute shrinkage and selection operator (Lasso) regression cross‐validation was used to determine the variables to include in the cox regression model. The training cohort was used to build the prediction model, and the validation cohort was used to further verify the discrimination, calibration, and clinical effectiveness of the model. Results A total of 2020 patients were included. The median OS was 56.50 months (95% CI, 50.36–62.65 months). In the training cohort of 1425 patients, through Lasso regression cross‐validation, 13 characteristics were included in the model. Cox proportional hazards model was developed and visualized as a nomogram. The C‐indexes of the model for predicting 1‐, 3‐, 5‐, and 10‐year OS were 0.848, 0.826, 0.814, and 0.799 in the training cohort and 0.851, 0.819, 0.814, and 0.801 in the validation cohort. The model showed great calibration in the two cohorts. Patients with a score of less than 274.29 had a better prognosis (training cohort: HR, 6.932; 95% CI, 5.723–8.397; log‐rank p

ObjectiveInterleukin-6 (IL-6) is a multiple-effect cell factor implicated in the etiopathogenesis of several rheumatologic disorders. The blockade of the IL-6 pathway via IL6R inhibitors effectively treats these disorders. However, the clinical significance of the IL6R blockade for ankylosing spondylitis (AS) therapy remains controversial. With advances in genomics, increasing evidence has revealed the role of heritability in the etiology of disease, and Mendelian randomization (MR) analyses are being used more broadly to infer causation. Therefore, this MR study aims to evaluate the potential therapeutic utility of IL6R-targeted approaches in AS.MethodsThe C-reactive protein (CRP) level was used as an exposure factor, and rheumatoid arthritis (RA) was used as a positive control. As-related genome-wide association study (GWAS) data were used as the primary outcome of drug-targeted MR analyses to test the relation between IL6R blockers and AS. Inverse variance weighting (IVW) is the primary analytical approach. Various sensitivity tests were performed to check the robustness and trustworthiness of the causality estimation, including consistency, heterogeneity, and pleiotropy analyses. In addition, repeated analysis was conducted using different GWAS data related to exposures and outcomes to examine the results for stability.ResultsAccording to the IVW results, IL6R inhibitors significantly reduced the risk of AS in ukb-b-18194 (OR: 0.995, 95% CI 0.993–0.996, P = 5.12 × 10−08) and ukb-a-88 (OR: 0.994, 95% CI 0.993–0.996, P = 6.25 × 10−15). Moreover, repeated analyses were performed using different exposure-related GWAS data, yielding similar results, ukb-b-18194 (OR: 0.995, 95% CI 0.993–0.997, P = 1.25 × 10−06) and ukb-a-88 (OR: 0.995, 95% CI 0.994–0.997, P = 7.81 × 10−09). Heterogeneity analyses and pleiotropy analyses indicated no significant heterogeneity or pleiotropy.ConclusionThis MR analysis result further validates that the IL-6 pathway may contribute to the pathogenesis of AS and that the inhibition of IL6R reduces the risk of AS. These findings may guide future studies and provide more favorable drug treatment options for people at high risk of AS.