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Abstract Objective To explore the correlation between changes in serum neurofilament light chain protein and clinical prognosis in patients with hypertensive intracerebral hemorrhage, combined with other clinical indicators. This article provides evidence for clinicians to effectively evaluate the prognosis of patients with hypertensive intracerebral hemorrhage and formulate diagnosis and treatment plans. Methods We selected 202 patients with hypertensive intracerebral hemorrhage admitted to different hospital from 2021 to 2022, and the clinical data of the patients were collected immediately after admission. Blood samples of the patients were collected, centrifuged, and the upper serum layer was collected and stored in the freezer at -80℃. During the same period, the sera of 30 age-matched healthy subjects were collected as the control group. The serum values of light chain protein of the experimental group and control group were measured by enzyme-linked immunosorbent assay. The Glasgow Outcome Scale of enrolled patients at 30 days of onset was recorded, and the collected data were statistically analyzed. Results After statistical treatment, systolic blood pressure, admission Glasgow coma scale score, hematoma volume, and serum light chain protein values on day 3 and day 7 were statistically significant between the groups with good prognosis and those with poor prognosis (all P

Abstract Genome-wide association studies have identified thousands of genetic variants associated with non-small cell lung cancer (NSCLC), however, it is still challenging to determine the causal variants and to improve disease risk prediction. Here, we applied massively parallel reporter assays to perform NSCLC variant-to-function mapping at scale. A total of 1249 candidate variants were evaluated, and 30 potential causal variants within 12 loci were identified. Accordingly, we proposed three genetic architectures underlying NSCLC susceptibility: multiple causal variants in a single haplotype block (e.g. 4q22.1), multiple causal variants in multiple haplotype blocks (e.g. 5p15.33), and a single causal variant (e.g. 20q11.23). We developed a modified polygenic risk score using the potential causal variants from Chinese populations, improving the performance of risk prediction in 450,821 Europeans from the UK Biobank. Our findings not only augment the understanding of the genetic architecture underlying NSCLC susceptibility but also provide strategy to advance NSCLC risk stratification.

Abstract Aqueous zinc ion batteries exhibit great prospects due to their low cost and high safety, while their lifespan is limited by severe dendritic growth problems. Herein, we develop an anti-dendrite hot-pressing separator interlayer through a mass-producible hot-pressing strategy, by spreading metal-organic framework (MOF) precursor on nonwoven matrix followed by a simple hot-pressing process. The in situ modification of MOF crystals on fiber surface processes abundant nitrogenous functional groups and high specific surface area (190.8 m2 g−1) with a strong attraction to Zn2+. These features contribute to a staged deposition behavior to promote uniform nucleation at high concentrations and two-dimensional grain growth at low concentrations. Consequently, Zn | |Zn symmetrical cells with hot-pressing separator interlayer demonstrate cycle lives of 3000 hours at 2 mA cm−2, 2 mAh cm−2. Moreover, Zn | |I2 pouch batteries with hot-pressing separator interlayer realizes 840 cycles lifespan with a capacity retention of 90.9% and a final discharge capacity of 110.6 mAh at 25 °C.

Strengthening conventional materials through additive manufacturing is generally understood to occur due to rapid cooling in the metallurgical process, which refines the microstructure by producing smaller grain sizes and segregating elements at specific locations. However, the effectiveness of this enhancement mechanism for increasing strength or elongation of parts depends significantly on the nature of the material. For example, austenitic 316L stainless steel fabricated by laser powder bed fusion exhibits superior ductility but struggles to improve its strength. In order to explore the contribution of grain scales and solute segregation in the strengthening of rapid solidification microstructures during additive manufacturing, we investigate an austenitic 316L stainless steel micro-alloyed with Nb and Ti. The austenitic stainless steel is strengthened through grain size refinement and the presence of dislocation cell boundaries enriched with Nb/Cr phases, leading to yield and tensile strengths exceeding 0.8 GPa and 1.1 GPa, respectively. Its strength exceeds that of most current additively manufactured austenitic stainless steels. The strong ferrite-forming components (Nb and Ti) contribute significantly to the microstructural refinement of austenitic stainless steels, with the average grain size decreased by 65.4% compared to austenitic 316L stainless steel. Additionally, the fine grains exhibit predominantly high-angle grain boundaries, and the elevated density of solute segregation in these regions plays a crucial role in contributing to exceptional strength of materials.

Failure of intraosseous prostheses is primarily attributed to implant loosening and infections. Current primary therapeutic modalities, such as antibiotics and local debridement, not only face challenges in thoroughly eliminating obstinate adhered bacteria but also encounter difficulties in ameliorating undue inflammatory reactions and regenerating impaired peri-implant bone tissues. Polyetheretherketone (PEEK) has excellent mechanical and physicochemical characteristics and has been used extensively as a medical biomaterial. However, the limited bactericidal and osseointegrative activities of bioinert PEEK restrict its clinical application. Herein, a microenvironment responsive coating with immobilised immunomodulatory magnesium ions (Mg2+) and disinfectant cerium oxide nanoparticles (CNPs) is designed via ion coordination mediated by polydopamine (PDA) and electrospinning based on collagen structure-bionic silk fibroin (SF). By utilising the pH responsiveness of SF, CNPs exhibit potent antibacterial effects in an acidic environment (pH 5.0) caused by local bacterial infection. Due to the chelation interaction with PDA and the constraint of SF, Mg2+ is slowly released, ameliorating the local immune microenvironment and boosting osteogenesis by upregulating M2 phenotype macrophages. Bioinformatics analysis indicates that the inflammation is suppressed via the NF-κB signaling pathway. Overall, this SF-based coating maximizes the synergistic effect of CNPs and Mg2+, offering enhanced antibacterial and osteoimmunomodulatory bioactivity for successful implantation.

The chitosan oligosaccharide and vanillin are used as raw materials to synthesize non-toxic and water-soluble chitosan oligosaccharide derivative called vanillin chitosan oligosaccharide as a green corrosion inhibitor. The corrosion inhibition properties of 20# steel in CO2-saturated solution system at 25°C and 3.5 wt% NaCl were studied. The synergistic effect of potassium iodide (KI) and VCOS on corrosion inhibition was also studied. Various techniques such as weight loss (WL), electrochemical analysis, atomic force microscopy (AFM), scanning electron microscopy (SEM), quantum chemical calculations, and molecular dynamics simulations were used to understand the inhibition properties. The inhibition efficiency of VCOS enhanced remarkably after the addition of KI, reaching an optimum value of 93.1%. EIS results showed that the inhibition of VCOS + KI on metal surface increased with time. Polarization measurements showed that VCOS and KI acted as mixed inhibitors by demonstrating anode dominance. SEM and AFM were used to study the formation of inhibition film on metal surface after 3 days immersion. We concluded that the mixed inhibitor followed Langmuir adsorption isotherm. In addition, quantum chemistry and molecular dynamics simulations were used to verify the relationship between corrosion inhibition efficiency and molecular structure.

Abstract Breast ultrasound is recommended for early breast cancer detection in China, but the rapid increase in imaging data burdens sonographers. This study evaluated the agreement between artificial intelligence (AI) software and sonographers in analyzing breast nodule features. Breast ultrasound images from two hospitals in Shanghai were analyzed by both the software and the sonographers for features including echotexture, echo pattern, orientation, shape, margin, calcification, and posterior echo attenuation. Agreement between software and sonographers was compared using the proportion of agreement and Kappa, with analysis time also evaluated. A total of 493 images were analyzed. The proportion of agreement between software and sonographers in assessing features was 80.5% for echotexture, 84.4% for echo pattern, 93.7% for orientation, 85.8% for shape, 88.6% for margin, 80.5% for calcification, and 90.5% for posterior echo attenuation, highlighting software’s high accuracy. Cohen’s kappa for other features indicated moderate to substantial agreement (0.411–0.674), with calcification showing fair agreement (0.335). The software significantly reduced analysis time compared to sonographers (P

Abstract This study aimed to quantify fundus microvascular alterations in patients requiring revascularization for coronary heart disease (CHD) using swept-source optical coherence tomography angiography (SS-OCTA) and to investigate the correlation between these alterations and the severity of coronary artery lesions. SS-OCTA was employed to assess the fundus neurovascular parameters of all participants, while the Gensini score was utilized to gauge the severity of coronary artery lesions in observation group. A total of 98 participants (49 CHD patients and 49 controls) were included. Analysis of the SS-OCTA parameters revealed that the vascular density (VD) of the superficial vascular plexus (SVP), the superficial vascular complex (SVC), the intermediate capillary plexus (ICP) in the parafoveal region, the mean ICP in the macula, deep capillary plexus (DCP) and deep vascular complex (DVC) in each macular region were significantly reduced in the observation group compared to the control group (P

Abstract Despite significant advancements in cancer immunotherapy, many patients continue to respond poorly. Novel therapeutic strategies and drugs are urgently needed. Here, we found that CYP2E1 is upregulated in M2 macrophages. The CYP2E1 inhibitor, Q11, could inhibit M2 macrophage polarization, while CYP2E1 overexpression could promote it. Increased levels of CYP2E1 and M2 macrophages in the tumor microenvironment of HCC patients correlate with poor prognosis. Q11 could inhibit tumor cells by targeting M2 macrophages rather than directly attacking tumor cells. Both Q11 and Cyp2e1 knockout could effectively suppress tumor growth. Q11 reduces the production of CYP2E1 metabolites ( ±)9(10)-DiHOME and ( ±)12(13)-DiHOME, thus attenuating PPARγ activation and M2 macrophage polarization. In summary, our findings suggest that Q11 could suppress M2 macrophage polarization by modulating the CYP2E1/( ±)9(10)-DiHOME or ( ±)12(13)-DiHOME/PPARγ axis, indicating that CYP2E1 may be a potential therapeutic target for HCC, and its inhibitor Q11 may be a potential drug for the treatment of HCC.

Abstract The autophagy pathway regulates the degradation of misfolded proteins caused by heat stress (HS) in the cytoplasm, thereby maintaining cellular homeostasis. Although previous studies have established that autophagy (ATG) genes are transcriptionally upregulated in response to HS, the precise regulation of ATG proteins at the subcellular level remains poorly understood. In this study, we provide compelling evidence for the translocation of key autophagy components, including the ATG1/ATG13 kinase complex (ATG1a, ATG13a), PI3K complex (ATG6, VPS34), and ATG8-PE system (ATG5), to HS-induced stress granules (SGs) in Arabidopsis thaliana. As HS subsides, SGs disassemble, leading to the re-translocation of ATG proteins back to the cytoplasm, thereby facilitating the rapid activation of autophagy to degrade HS-induced ubiquitinated aggregates. Notably, autophagy activation is delayed in the SG-deficient (ubp1abc) mutants during the HS recovery phase, resulting in an insufficient clearance of ubiquitinated insoluble proteins that arise due to HS. Collectively, this study uncovers a previously unknown function of SGs in regulating autophagy as a temporary repository for ATG proteins under HS and provides valuable insights into the cellular mechanisms that maintain protein homeostasis during stress.

Context: Berberine (BBR) can regulate enteric glial cells (EGCs) and the gut vascular barrier (GVB).Objective: To explore whether BBR regulates GVB permeability via the S100B pathway.Materials and methods: GVB hyperpermeability in C57BL/6J mice was induced by burns or S100B enema. BBR (25 or 50 mg/kg/d, 3 d) was gavaged preburn. S100B monoclonal antibody (S100BmAb) was i.v. injected postburn. Mouse intestinal microvascular endothelial cells (MIMECs) were treated with S100B, S100B plus BBR, or Z-IETD-FMK. GVB permeability was assayed by FITC-dextran, S100B by ELISA, caspase-8, β-catenin, occludin and PV-1 by immunoblot.Results: Burns elevated S100B in serum and in colonic mucosa to a peak (147.00 ± 4.95 ng/mL and 160.30 ± 8.50 ng/mg, respectively) at 36 h postburn, but BBR decreased burns-induced S100B in serum (126.20 ± 6.30 or 90.60 ± 3.78 ng/mL) and in mucosa (125.80 ± 12.40 or 91.20 ± 8.54 ng/mg). Burns raised GVB permeability (serum FITC-dextran 111.40 ± 8.56 pg/mL) at 48 h postburn, but BBR reduced GVB permeability (serum FITC-dextran 89.20 ± 6.98 or 68.60 ± 5.50 ng/mL). S100B enema (1 μM) aggravated burns-raised GVB permeability (142.80 ± 8.07 pg/mL) and PV-1, but the effect of S100B was antagonized by BBR. Z-IETD-FMK (5 μM) increased S100B-induced permeability to FITC-dextran (205.80 ± 9.70 to 263.80 ± 11.04 AUs) while reducing β-catenin in MIMECs. BBR (5 μM) reduced S100B-induced permeability (104.20 ± 9.65 AUs) and increased caspase-8, β-catenin and occludin.Discussion and conclusion: BBR decreases burns-induced GVB hyperpermeability via modulating S100B/caspase-8/β-catenin pathway and may involve EGCs.

This study investigates the hot deformation behavior and microstructural evolution of wire arc additive manufactured (WAAMed) NiTi alloy. Hot deformation tests were conducted within a temperature range of 750–900 °C and a strain rate range of 0.01–5 s−1, achieving a height reduction of up to 50%. The Strain-Compensated Arrhenius-Type (SCAT) model and deformation processing maps were developed. The microstructures of compression specimens at strain rates of 0.01 s−1 and temperatures of 750–900 °C were characterized. The results demonstrate that the flow stress of WAAMed NiTi alloys increases with increasing strain rate and decreases with increasing deformation temperature. The calculated values from the SCAT model align closely with the experimental values, indicating a reliable analysis with high prediction accuracy. Flow instability region expands as the degree of deformation increases, and the optimal processing windows for the studied alloy are concentrated within the range of 800–900 °C and 0.01–0.05 s−1. In the deformed WAAMed NiTi alloys, the proportion of low-angle grain boundaries is around 70% and the recrystallized grain fraction remains below 15%. This is attributed to the predominance of dynamic recovery behavior in the softening mechanism. Discontinuous dynamic recrystallization and continuous dynamic recrystallization as auxiliary softening mechanisms are also involved in the softening of NiTi alloys, leading to a steady state of flow behavior.

Abstract Emojis, utilizing visual means, mimic human facial expressions and postures to convey emotions and opinions. They are widely used in social media platforms such as Sina Weibo, and have become a crucial feature for sentiment analysis. However, existing approaches often treat emojis as special symbols or convert them into text labels, thereby neglecting the rich visual information of emojis. We propose a novel multimodal information integration model for emoji microblog sentiment analysis. To effectively leverage the emoji visual information, the model employs a text-emoji visual mutual attention mechanism. Experiments on a manually annotated microblog dataset show that compared to the baseline models without incorporating emoji visual information, the proposed model achieves improvements of 1.37% in macro F1 score and 2.30% in accuracy, respectively. To facilitate the related research, our corpus will be publicly available at https://github.com/yx100/Emojis/blob/main/weibo-emojis-annotation .

Abstract LC3-associated phagocytosis (LAP) is critical in host defense against invading pathogens, but the molecular mechanism for LAP activation is still unclear. Here, we find programmed cell death 6 (PDCD6) as a negative regulator of LAP. PDCD6 deficiency in mice and macrophages induces enhanced bactericidal activity and LAP formation. In parallel, lactate dehydrogenase A (LDHA) activity and lactate production is induced in macrophages challenged with bacteria, Zymosan or Pam3CSK4, while genetic ablation or pharmacological inhibition of LDHA reduces lactate levels and impairs bactericidal activity in vivo and in vitro. Mechanistically, PDCD6 interacts with LDHA to downregulate lactate metabolism, leading to reduced RUBCN lactylation at lysine33 (K33). By contrast, PDCD6-deficiency increases RUBCN lactylation, thereby promotes RUBCN interaction with VPS34, LAP formation, and protective responses. Our results thus suggest a PDCD6-LDHA-lactate-RUBCN axis of innate immunity regulation that may both contribute to protection from infectious diseases and serve as targets for therapeutic development.

As the global demographic shifts toward an aging population, understanding the efficiency of protein utilization in older adults becomes crucial. Our study explores the intricate relationship between protein intake and aging, with a focus on precision nutrition for older people. Through a meta-analysis, we confirm a decline in protein-utilization capacity in older individuals and examine the different contributions of plant and animal protein. In experiments involving mice of different ages, older mice exhibited decreases in the biological utilization of four proteins (casein, beef protein, soy protein, and gluten), particularly casein. In subsequent research, casein was studied as a key protein. A decline in gastric digestion function was observed through peptidomics and the examination of pepsin levels using casein. Nevertheless, this decline did not significantly affect the overall protein digestion during the aging process. The combined application of targeted amino acid metabolomics identified abnormal absorption of amino acids as the underlying cause of decreased protein utilization during aging, particularly emphasizing a reduction in branched-chain amino acids (BCAAs) in older mice. Delving deeper into the proteomics of the intestinal protein digestion and absorption pathway, a reduction of over 60% in large neutral amino acid transporter 2 (LAT2) protein expression was observed in both older humans and aged mice. The reduction in LAT2 protein was found to be a key factor influencing the diminished BCAA availability. Overall, our study establishes the significance of amino acid absorption through LAT2 in protein utilization during aging and offers a new theoretical foundation for improving protein utilization in the older adults.

The influence of confining pressure on the dynamic fracture mechanical behavior of deep rock masses is crucial in the exploitation of deep resources and the development of underground spaces. In this study, dynamic caustics experiments were conducted using transparent epoxy resin materials to investigate the crack propagation behavior and interaction mechanisms of double cracks under confinement. The experimental results indicate that biaxial confining pressure suppresses crack propagation, interaction between double cracks, and penetration. Without confining pressure, cracks do not penetrate until the relative vertical distance ΔH between crack tips is 20 mm, whereas with confining pressure, cracks cease to penetrate when the relative vertical distance between crack tips is 10 mm; however, interaction between crack tips still exists at this point. During the crack interaction stage, both fracture toughness and propagation velocity of crack tips exhibit significant fluctuations under no confining pressure conditions, whereas under confining pressure, both decrease rapidly. Additionally, under confining pressure conditions, the fluctuation range of crack propagation direction during crack interaction is relatively small. Confining pressure rapidly reduces the degree of stress concentration at crack tips, increases the rate of energy release at crack tips, and enhances the ability of dynamic cracks to resist the influence of other crack tips or crack surfaces. Under confining pressure, continuous Rayleigh waves are typically observed at crack tips due to an imbalance between stored strain energy and the energy release rate. These waves dissipate part of the strain energy, promoting crack deflection and branching.

Fueled by substantial advancements in deep learning, the domain of autonomous driving is swiftly advancing towards more robust and effective intelligent systems. One of the critical challenges in this field is achieving accurate 3D object detection, which is often hindered by data sparsity and occlusion. To address these issues, we propose a method centered around a multi-modal fusion strategy that leverages vehicle-road cooperation to enhance perception capabilities. Our approach integrates label information from roadside perception point clouds to harmonize and enrich the representation of image and LiDAR data. This comprehensive integration significantly improves detection accuracy by providing a fuller understanding of the surrounding environment. Rigorous evaluations of our proposed method on two benchmark datasets, KITTI and Waymo Open, demonstrate its superior performance, with our model achieving 87.52% 3D Average Precision (3D AP) and 93.71% Bird’s Eye View Average Precision (BEV AP) on the KITTI val set. These results highlight the effectiveness of our method in detecting sparse and distant objects, contributing to the development of safer and more efficient autonomous driving solutions.

Abstract We report a case of disseminated cryptococcosis, an uncommon fungal infection predominantly affecting the lungs and central nervous system, with the rare involvement of adrenal cryptococcosis, compounded by meningitis and pneumonia. The patient, previously diagnosed with primary myelofibrosis and undergoing oral Ruxolitinib treatment, exhibited immunosuppression. Imaging via chest and abdominal CT scans revealed inflammation in the right lung’s middle lobe, splenomegaly, a splenic lesion, and a left adrenal mass, initially prompting considerations of pheochromocytoma. However, unilateral adrenalectomy and subsequent pathological examination disclosed extensive infiltration by inflammatory and multinucleate giant cells, with Periodic acid-Schiff (PAS) staining confirming the diagnosis. The identification of adrenal cryptococcosis was further supported by positive adrenal pus culture and significantly elevated capsular antigens in both serum and cerebrospinal fluid, at titers of 1:2560. Following a month of oral antifungal treatment, marked reductions in capsular antigen levels were noted, to 1:640 and 1:160 in serum and cerebrospinal fluid, respectively. The patient was discharged on a regimen of oral amphotericin B, flucytosine, and fluconazole, with regular outpatient follow-ups showing no signs of recurrence or dissemination.

Abstract Morphogens play a critical role in coordinating stress adaptation and aging across tissues, yet their involvement in neuronal mitochondrial stress responses and systemic effects remains unclear. In this study, we reveal that the transforming growth factor beta (TGF-β) DAF-7 is pivotal in mediating the intestinal mitochondrial unfolded protein response (UPRmt) in Caenorhabditis elegans under neuronal mitochondrial stress. Two ASI sensory neurons produce DAF-7, which targets DAF-1/TGF-β receptors on RIM interneurons to orchestrate a systemic UPRmt response. Remarkably, inducing mitochondrial stress specifically in ASI neurons activates intestinal UPRmt, extends lifespan, enhances pathogen resistance, and reduces both brood size and body fat levels. Furthermore, dopamine positively regulates this UPRmt activation, while GABA acts as a systemic suppressor. This study uncovers the intricate mechanisms of systemic mitochondrial stress regulation, emphasizing the vital role of TGF-β in metabolic adaptations that are crucial for organismal fitness and aging during neuronal mitochondrial stress.

Abstract Jujube (Ziziphus jujuba Mill.), belonging to the Rhamnaceae family, is gaining increasing prominence as a perennial fruit crop with significant economic and medicinal values. Here, we conduct de novo assembly of four reference-grade genomes, encompassing one wild and three cultivated jujube accessions. We present insights into the population structure, genetic diversity, and genomic variations within a diverse collection of 1059 jujube accessions. Analyzes of the jujube pan-genome, based on our four assemblies and four previously released genomes, reveal extensive genomic variations within domestication-associated regions, potentially leading to the discovery of a candidate gene that regulates flowering and fruit ripening. By leveraging the pan-genome and a large-scale resequencing population, we identify two candidate genes involved in domestication traits, including the seed-setting rate, the bearing-shoot length and the leaf size in jujube. These genomic resources will accelerate evolutionary and functional genomics studies of jujube.

Background: The breeding of high-quality, high-yield, and disease-resistant varieties is closely related to food security. The investigation of breeding results relies on the evaluation of seed phenotype, which is a key step in the process of breeding. In the global digitalization trend, digital technology based on optical sensors can perform the digitization of seed phenotype in a non-contact, high throughput way, thus significantly improving breeding efficiency. Aim of review: This paper provides a comprehensive overview of the principles, characteristics, data processing methods, and bottlenecks associated with three digital technique types based on optical sensors: spectroscopy, digital imaging, and three-dimensional (3D) reconstruction techniques. In addition, the applicability and adaptability of digital techniques based on the optical sensors of maize seed phenotype traits, namely external visible phenotype (EVP) and internal invisible phenotype (IIP), are investigated. Furthermore, trends in future equipment, platform, phenotype data, and processing algorithms are discussed. This review offers conceptual and practical support for seed phenotype digitization based on optical sensors, which will provide reference and guidance for future research. Key scientific concepts of review: The digital techniques based on optical sensors can perform non-contact and high-throughput seed phenotype evaluation. Due to the distinct characteristics of optical sensors, matching suitable digital techniques according to seed phenotype traits can greatly reduce resource loss, and promote the efficiency of seed evaluation as well as breeding decision-making. Future research in phenotype equipment and platform, phenotype data, and processing algorithms will make digital techniques better meet the demands of seed phenotype evaluation, and promote automatic, integrated, and intelligent evaluation of seed phenotype, further helping to lessen the gap between digital techniques and seed phenotyping.

Abstract Lettuce (Lactuca sativa L., Asteraceae) is one of the most important vegetable crops, known for its various horticultural types and significant morphological variation. The first reference genome of lettuce, a crisphead type (L. sativa var. capitata cv. Salinas), was previously released. Here, we reported a near-complete chromosome-level reference genome for looseleaf lettuce (L. sativa var. crispa). PacBio high-fidelity sequencing, Oxford Nanopore, and Hi-C technologies were employed to produce genome assembly. The final assembly is 2.59 Gb in length with a contig N50 of 205.47 Mb, anchored onto nine chromosomes, containing 14 recognizable telomeres and only 11 gaps. Repetitive sequences account for 77.11% of the genome, and 41,375 protein-coding genes were predicted, with 99.10% of these assigned functional annotations. This chromosome-level genome enriched genomic resources for various horticultural types of lettuce and will facilitate the characterization of morphological variation and genetic improvement in lettuce.

Abstract Liposomal irinotecan has shown promising antitumor activity in patients with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) who have undergone prior gemcitabine-based therapies. This randomized, double-blind, parallel-controlled, multicenter phase 3 study (NCT05074589) assessed the efficacy and safety of liposomal irinotecan HR070803 combined with 5-fluorouracil (5-FU) and leucovorin (LV) in this patient population. Patients with unresectable, locally advanced, or metastatic PDAC who had previously received gemcitabine-based therapies were randomized 1:1 to receive either HR070803 (60 mg/m2 anhydrous irinotecan hydrochloride, equal to 56.5 mg/m2 free base) or placebo, both in combination with 5-FU (2000 mg/m2) and LV (200 mg/m2), all given intravenously every two weeks. The primary endpoint of the study was overall survival (OS). A total of 298 patients were enrolled and received HR070803 plus 5-FU/LV (HR070803 group, n = 149) or placebo plus 5-FU/LV (placebo group, n = 149). Median OS was significantly improved in the HR070803 group compared to the placebo group (7.4 months [95% CI 6.1–8.4] versus 5.0 months [95% CI 4.3–6.0]; HR 0.63 [95% CI 0.48–0.84]; two-sided p = 0.0019). The most common grade ≥ 3 adverse events in the HR070803 group were increased gamma-glutamyltransferase (19.0% versus 11.6% in placebo group) and decreased neutrophil count (12.9% versus 0 in placebo group). No treatment-related deaths occurred in the HR070803 group, while the placebo group reported one treatment-related death (abdominal infection). HR070803 in combination with 5-FU/LV has shown promising efficacy and manageable safety in advanced or metastatic PDAC in the second-line setting, representing a potential option in this patient population.

Abstract Disruption of ciliary homeostasis in vascular endothelial cells has been implicated in the development of atherosclerosis. However, the molecular basis for the regulation of endothelial cilia during atherosclerosis remains poorly understood. Herein, we provide evidence in male mice that the accumulation of lipid droplets in vascular endothelial cells induces ciliary loss and contributes to atherosclerosis. Triglyceride accumulation in vascular endothelial cells differentially affects the abundance of free fatty acid species in the cytosol, leading to stimulated lipid droplet formation and suppressed protein S-palmitoylation. Reduced S-palmitoylation of ciliary proteins, including ADP ribosylation factor like GTPase 13B, results in the loss of cilia. Restoring palmitic acid availability, either through pharmacological inhibition of stearoyl-CoA desaturase 1 or a palmitic acid-enriched diet, significantly restores endothelial cilia and mitigates the progression of atherosclerosis. These findings thus uncover a previously unrecognized role of lipid droplets in regulating ciliary homeostasis and provide a feasible intervention strategy for preventing and treating atherosclerosis.

Abstract Aims This study is designed to identify risk factors of postoperative nausea and vomiting (PONV) in patients after gynecologic laparoscopic surgery and establish a nomogram model. Methods In this retrospective and multicenter study, we collected and analyzed data from 1233 patients who underwent gynecologic laparoscopic surgery. The Lasso algorithm was used to optimize the selection of independent variables in the development group. Multivariate logistic regression analysis was used to explore the risk factors of PONV to develop the predictive nomogram model. Finally, we used an internal and external verification group and machine learning (ML) to evaluate the accuracy and clinical applicability of the model. Results The dosage of sufentanil in patient-controlled intravenous analgesia (PCIA), the dosage of remifentanil, the use of neostigmine, duration of surgery and the maximum value of the PETCO2 were risk factors of PONV in patients after gynecologic laparoscopic surgery. In contrast, the dosage of propofol during the surgery and the use of steroids were protective factors. The nomogram was then established to predict the incidence of PONV in these patients based on the above eight indicators. The C-index of the development group, internal, and external verification groups are 0.802, 0.857, and 0.966, respectively. Conclusion A nomogram model was developed to predict the incidence of PONV in patients after gynecologic laparoscopic surgery. This model was found to be reliable and of high clinical value.

Segmentation of point clouds is foundational to numerous remote sensing applications. Recently, the development of Transformers has further improved segmentation techniques thanks to their great long-range context modeling capability. However, Transformers have quadratic complexity in inference time and memory, which both limits the input size and poses a strict hardware requirement. This paper presents a novel 3D-UMamba network with linear complexity, which is the earliest to introduce the Selective State Space Model (i.e., Mamba) to multi-source LiDAR point cloud processing. 3D-UMamba integrates Mamba into the classic U-Net architecture, presenting outstanding global context modeling with high efficiency and achieving an effective combination of local and global information. In addition, we propose a simple yet efficient 3D-token serialization approach (Voxel-based Token Serialization, i.e., VTS) for Mamba, where the Bi-Scanning strategy enables the model to collect features from all input points in different directions effectively. The performance of 3D-UMamba on three challenging LiDAR point cloud datasets (airborne MultiSpectral LiDAR (MS-LiDAR), aerial DALES, and vehicle-mounted Toronto-3D) demonstrated its superiority in multi-source LiDAR point cloud semantic segmentation, as well as the strong adaptability of Mamba to different types of LiDAR data, exceeding current state-of-the-art models. Ablation studies demonstrated the higher efficiency and lower memory costs of 3D-UMamba than its Transformer-based counterparts.

Various soil management strategies based on chemical, physical, and biological principles are used to manipulate soil microbial communities to improve plant health. However, how the microbial communities that are altered by these strategies respond to pathogen invasion and contribute to plant health remains poorly understood. Here, we investigated the effects of representative chemical, physical, and biological strategies, namely, chemical fumigation (CF), heat disinfestation (HE), and reductive soil disinfestation (RSD), on soil microbial communities, pathogen invasion, and plant performance. Our results revealed a strong relationship between variations in soil microbial communities and their impact on pathogen inhibition and plant health under the different strategies. Physicochemical management effectively decreased the density of Fusarium oxysporum, thereby suppressing the outbreak of Fusarium wilt. However, these strategies also decreased fungal density, bacterial diversity, network complexity, and core microbiome stability, resulting in diminished pathogen resistance and the recurrence of plant disease upon pathogen reinoculation. In contrast, biological management was the most effective strategy for the suppression of pathogen invasion and the improvement of plant health. Biological management optimized the bacterial and core microbiomes, leading to increased bacterial diversity and stimulated the growth of potential disease-suppressive agents, which contributed to resistance to F. oxysporum invasion and consistently prompted plant health. Taken together, our results reveal that physicochemical (CF and HE) and biological strategies (RSD) contribute to plant health via different mechanisms. In addition, this study provides empirical evidence for the significant impact of biological management on the manipulation of the core microbiome and its critical role in plant health.

Hyperspectral anomaly detection (HAD) holds significant importance in remote sensing image processing and has been recently empowered by deep learning-based methods. Despite achieving good performance by reconstructing the background and suppressing abnormal targets, these methods often fail to distinguish the attributes of latent features during background reconstruction, resulting in unsatisfactory reconstruction quality. This occurs because the background usually has low-frequency properties and the anomalies have high-frequency properties, so these issues should be considered during background reconstruction. To overcome this weakness, a multi-scale frequency-guided two-stream network (MFTNet) is proposed for HAD. Firstly, considering the different frequency attributes of background and anomalies, we use an encoder to extract features and then design a multi-scale frequency decomposition module to decompose the features into high-frequency (HF) part for anomalies and the low-frequency (LF) part for background. Furthermore, different from anomaly suppression-based methods, we introduce a high-frequency enhancement module to highlight abnormal targets in the HF part, making them stand out in the background. Meanwhile, the features from the encoder contain more background information, so we fuse the encoded features and LF part features by a self-attention module to accurately recover the background. Finally, we perform anomaly detection on the reconstructed anomaly and background parts, respectively, and the average of those two results is the final detection map. Comparative analysis on six datasets against thirteen baseline methods, including seven effective deep learning-based methods, demonstrates that our proposed MFTNet delivers competitive detection results. The code of this work will be released at: https://github.com/xautzhaozhe/MFTNet.

Nickel-based superalloys are indispensable in aerospace engines due to their exceptional high-temperature strength, oxidation resistance, and corrosion resistance, making them critical for joining processes such as inertia friction welding (IFW), which is favored for its efficiency and superior joint quality. In this study, IFW was used to join FGH101 powder superalloy with IN718 deformed superalloy, resulting in significant plastic deformation that formed symmetrical ear-shaped flash on the IN718 side and minor upsetting on the FGH101 side, with a wavy interface due to heat dissipation. Microhardness analysis revealed higher hardness at the weld interface, followed by a sharp decline near the Heat Affected Zone (HAZ) on the IN718 side due to phase re-dissolution, while FGH101 showed quicker recovery. Post-weld aging treatments enhanced hardness and strength through γ′ and δ phase precipitation in FGH101 and γ″ phases in IN718. Room temperature tensile tests demonstrated impressive strength with failures occurring plastically within the IN718 base metal, whereas elevated temperatures shifted failure locations to the weld zone without necking. Fatigue tests exhibited varied lifespans, with fractures initiating either at stress concentrators or within the FGH101 base metal far from the weld center. Scanning electron microscope (SEM) analysis confirmed mixed-mode fracture patterns, underscoring the importance of microstructure on joint performance and suggesting that optimizing IFW parameters can lead to superior weld quality in aerospace components, thus providing valuable insights for future research and industrial applications.

Abstract Solid oxide cells (SOCs) are promising energy‐conversion devices due to their high efficiency under flexible operational modes. Yet, the sluggish kinetics of fuel electrodes remain a major obstacle to their practical applications. Since the electrochemically active region only extends a few micrometers, manipulating surface architecture is vital to endow highly efficient and stable fuel electrodes for SOCs. Herein, a simple selective etching method of nanosurface reconstruction is reported to achieve catalytically optimized hierarchical morphology for boosting the SOCs under different operational modes simultaneously. The selective etching can create many corrosion pits and exposure of more B‐site active atoms in Sr2Co0.4Fe1.2Mo0.4O6‐δ fuel electrode, as well as promote the exsolution of CoFe alloy nanoparticles. An outstanding electrochemical performance of the fabricated cell with the power density increased by 1.47 times to 1.31 W cm−2 at fuel cell mode is demonstrated, while the current density reaches 1.85 A cm−2 under 1.6 V at CO2 electrolysis mode (800 °C). This novel selective etching method in perovskite oxides provides an appealing strategy to fabricate hierarchical electrocatalysts for highly efficient and stable SOCs with broad implications for clean energy systems and CO2 utilization.

PurposeThis study aims to evaluate the effectiveness and safety of prophylactic hyperthermic intraperitoneal chemotherapy (P-HIPEC) in patients with locally advanced gastric cancer (AGC) after laparoscopic radical gastrectomy. Additionally, it explores how the frequency and timing of P-HIPEC influence treatment outcomes.MethodsA retrospective analysis was conducted on 227 patients with locally AGC who underwent laparoscopic surgery at Maoming People’s Hospital from January 2016 to December 2022. Patients were stratified into the HIPEC group (n=101) and the non-HIPEC group (n=126), based on whether they received postoperative P-HIPEC. Propensity score matching (PSM) was used to adjust for baseline characteristics, facilitating a comparative analysis of survival outcomes, postoperative complications and recurrence patterns. Cox regression analysis was performed to identify prognostic factors. Furthermore, the impact of varying P-HIPEC frequencies and initiation timings was evaluated.ResultsNo significant differences in overall survival (OS) or postoperative complication rates were observed between the two groups in the original and PSM cohorts. But the disease-free survival (DFS) of the HIPEC group was significantly higher than that of the non-HIPEC group (HR 0.569; 95% CI 0.362–0.894; p = 0.013) in the PSM cohort, with 1-year, 3-year, and 5-year DFS rates showing notable improvement (77.9% vs. 69.7%, 60.1% vs. 43.0%, and 46.2% vs. 25.5%). The incidence of isolated peritoneal metastasis (PM) was significantly lower in the HIPEC group (5.3% vs. 17.3%, p = 0.039). Multivariate Cox regression analysis identified P-HIPEC as an independent protective factor for DFS. Further analysis indicated that neither the number of P-HIPEC sessions had a significant impact on OS (p = 0.388) or DFS (p = 0.735), nor did the timing of P-HIPEC initiation affect OS (p = 0.620) or DFS (p = 0.488). Likewise, different P-HIPEC frequencies or initiation timings had no significant impact on postoperative complication rates or recurrence patterns.ConclusionP-HIPEC effectively reduces the risk of postoperative PM and improves DFS in patients with locally AGC without increasing postoperative complications. However, it does not significantly impact OS. Additionally, variations in the frequency and timing of P-HIPEC initiation do not significantly affect survival outcomes, postoperative complications, or recurrence patterns.

Long segment ureteral reconstruction has always posed a challenge for surgeons. We report the case of a 49 years male patient with a right ureteral obstruction between the ileal orthotopic bladder and the ureter. The patient underwent a 12cm ureteral reconstruction with the prepuce. One month after the surgery, anterograde angiography through the nephrostomy tube showed ureteral patency. After one year of postoperative follow-up, the patient's ureteral stricture did not recur. Using the prepuce as a free graft for ureteral reconstruction is one of the available options.

Ischemia-reperfusion injury (IRI) commonly occurs in clinical settings, particularly in medical practices such as organ transplantation, cardiopulmonary resuscitation, and recovery from acute trauma, posing substantial challenges in clinical therapies. Current systemic therapies for IRI are limited by poor drug targeting, short efficacy, and significant side effects. Owing to their exceptional biocompatibility, biodegradability, excellent mechanical properties, targeting capabilities, controlled release potential, and properties mimicking the extracellular matrix (ECM), hydrogels not only serve as superior platforms for therapeutic substance delivery and retention, but also facilitate bioenvironment cultivation and cell recruitment, demonstrating significant potential in IRI treatment. This review explores the pathological processes of IRI and discusses the roles and therapeutic outcomes of various hydrogel systems. By categorizing hydrogel systems into depots delivering therapeutic agents, scaffolds encapsulating mesenchymal stem cells (MSCs), and ECM-mimicking hydrogels, this article emphasizes the selection of polymers and therapeutic substances, and details special crosslinking mechanisms and physicochemical properties, as well as summarizes the application of hydrogel systems for IRI treatment. Furthermore, it evaluates the limitations of current hydrogel treatments and suggests directions for future clinical applications.

Production of melanin pigments is a protective mechanism of the skin against ultraviolet (UV)-induced damage and carcinogenesis. However, the molecular basis for melanogenesis is still poorly understood. Herein, we demonstrate a critical interplay between the primary cilium and the melanocortin 1 receptor (MC1R) signaling. Our data show that UV and α-melanocyte-stimulating hormone (α-MSH) trigger cilium formation in human melanocytes and melanoma cells. Deficiency of MC1R or the presence of its red hair color (RHC) variations significantly attenuates the UV/α-MSH-induced ciliogenesis. Further investigation reveals that MC1R enters the cilium upon UV/α-MSH stimulation, which is facilitated by the interaction of MC1R with the BBSome and the palmitoylation of MC1R. MC1R interacts with the BBSome through the second and third intercellular loops, which contain the common RHC variant alleles (R151C and R160W). These RHC variants of MC1R exhibit attenuated ciliary localization, and enforced ciliary localization of these variants elevates melanogenesis. Ciliary MC1R triggers a sustained cAMP signaling and selectively stimulates Sox9, which appears to up-regulate melanogenesis-related genes as the transcriptional cofactor for MITF. These findings reveal a previously unrecognized nexus between MC1R and cilia and suggest an important mechanism for RHC variant-related pigmentary defects.

ABSTRACT: The avian infectious bronchitis virus (IBV) poses a significant economic threat to the global poultry industry. Although in recent years, the GVI-1 lineage of IBV has proliferated throughout China, there is still a lack of comprehensive studies regarding the pathogenicity of this lineage, particularly with respect to infections of the digestive tract and the antigenic characteristics of the S1 gene. In this study, we investigated the effects of infecting 14-day-old chicks with the HX strain of the GVI-1 lineage over a 14-d period postinfection. Assessment of the pathogenicity of the HX strain included clinical observations; monitoring of body weight, organ viral load, viral shedding, and gross anatomy; histopathological analysis, and bioinformatics-based antigenic characterization of the S1 protein. The findings revealed that compared with previously reported GVI-1 lineage strains, the HX strain is characterized by greater virulence, with infection leading to approximately 26% mortality and extensive severe organ damage, including that of the proventriculus and kidneys. Moreover, at 14 d postinfection, 80% of oral swabs and 100% of cloacal swabs from chickens infected with the HX strain tested positive, indicating a prolonged period of viral shedding relative to that previously reported for GVI-1 lineage strains. Bioinformatic analysis of B-cell epitopes on the S1 protein revealed 7 potential antigenic epitopes. Collectively, our findings in this study provide clear evidence to indicate that compared previously reported GVI-1 lineage strains, chicks infected with the IBV GVI-1 lineage strain HX are characterized by heightened rates of mortality, more pronounced organ damage, and an extended period of viral shedding. This comprehensive characterization highlights the pathogenic potential of the GVI-1 lineage and its capacity to induce severe kidney and proventriculus damage, thereby emphasizing the imperative of early initiated preventive measures. Furthermore, on the basis of our analysis of the antigenic properties of the S1 protein, we have identified 7 potential linear B-cell epitopes, which will provide valuable insights for the development of epitope-based vaccines.

Abstract Phagocytosis of shed photoreceptor outer segments by the retinal pigment epithelium (RPE) is essential for retinal homeostasis. Dysregulation of the phagocytotic process is associated with irreversible retinal degenerative diseases. However, the molecular mechanisms underlying the phagocytic activity of RPE cells remain elusive. In an effort to uncover proteins orchestrating retinal function, the cylindromatosis (CYLD) deubiquitinase is identified as a critical regulator of photoreceptor outer segment phagocytosis. CYLD‐deficient mice exhibit abnormal retinal structure and function. Mechanistically, CYLD interacts with enkurin domain containing protein 1 (ENKD1) and deubiquitinates ENKD1 at lysine residues K141 and K242. Deubiquitinated ENKD1 interacts with Ezrin, a membrane‐cytoskeleton linker, and stimulates the microvillar localization of Ezrin, which is essential for the phagocytic activity of RPE cells. These findings thus reveal a crucial role for the CYLD‐ENKD1‐Ezrin axis in regulating retinal homeostasis and may have important implications for the prevention and treatment of retinal degenerative diseases.

Schizothorax lissolabiatus and Schizothorax griseus are native Chinese fish species with significant ecological and economic importance. We wanted to support sustainable aquaculture practices by exploring the differences in metabolic, histological, and microbiota between the two Schizothorax species. This study analyzed and compared the digestive enzyme activities, metabolic indicators, gut histology, and microbiota composition of S. lissolabiatus and S. griseus under identical farming conditions. Our comparative analysis reveals both shared characteristics and species-specific differences. While a-amylase and trypsin activities showed no significant differences between species, a consistent trend was observed, with enzyme activity highest in the hindgut, followed by the midgut, foregut, esophagus, and liver. In terms of specific metabolic markers, S. griseus shows higher lipase activity in the liver and foregut, as well as higher aspartate aminotransferase and catalase levels in the liver, along with an increased serum glucose content compared to S. lissolabiatus. Serum metabolomics analysis revealed 21 differentially abundant metabolites linked to glycerophospholipid metabolism, autophagy, purine metabolism, and necroptosis, reflecting distinct metabolic adaptations and nutritional needs for each species. These metabolic differences provide a basis for optimizing feed composition and aquaculture practices tailored to each species. Notably, S. lissolabiatus displays a significantly higher goblet cell count in the hindgut compared to S. griseus. Additionally, both species exhibit greater villi number, length, width, crypt depth, and muscle thickness in the esophagus than in the foregut, midgut, and hindgut. S. griseus also has a higher number of operational taxonomic units (OTUs) and greater microbial diversity in its intestinal microbiota, which may enhance its nutrient utilization capabilities. While both species’ dominant microbial phyla include Fusobacteria, Firmicutes, Proteobacteria, and Bacteroidetes, S. griseus demonstrated superior lipid digestion capabilities. Furthermore, the midgut and hindgut in both species display higher starch and protein digestive enzyme activities than other digestive tissues. These findings highlight the physiological differences between the two Schizothorax species, suggesting targeted strategies to improve health, growth, and sustainability in aquaculture.

Background: Hemoporfin-mediated photodynamic therapy (Hemoporfin-PDT) is considered a safe and effective treatment for port-wine stains (PWS). This study aims to investigate the influence of prior pulse dye laser (PDL) treatments history on the effectiveness of Hemoporfin-PDT in young children aged 1–3 years with PWS. Methods: Data was gathered for individuals with PWS aged 1–3 years who received two or more Hemoporfin-PDT treatments. The study population was stratified into two groups: Cohort 1 (No PDL) comprised patients without a history of PDL treatment, while Cohort 2 (Prior PDL) consisted of patients with a history of PDL treatment. An analysis was conducted to investigate the relationship between treatment efficacy and variables including gender, age, location, and type of PWS. Results: There were a total of 220 cases in the No PDL group and 53 cases in the Prior PDL group. It was observed that prior PDL treatment history did not impact the efficacy of Hemoporfin-PDT in treating PWS among young children. Both the type and location of PWS significantly influence the clinical effectiveness of Hemoporfin-PDT for PWS (P = 0.040, P < 0.001), while gender and age show no association with treatment outcomes (P > 0.05). Notably, the peripheral face might be an independent influencing factor for high efficacy of Hemoporfin-PDT of the facial regions (P < 0.05). Conclusion: Previous PDL treatment history does not impact the effectiveness of Hemoporfin-PDT therapy in young children with PWS.

Colorectal cancer (CRC) ranks among the most prevalent gastrointestinal tumors globally and poses a significant threat to human health. In recent years, tumor organoids have emerged as ideal models for clinical disease research owing to their ability to closely mimic the original tumor tissue and maintain a stable phenotypic structure. Organoid technology has found widespread application in basic tumor research, precision therapy, and new drug development, establishing itself as a reliable preclinical model in CRC research. This has significantly advanced individualized and precise tumor therapies. Additionally, the integration of single-cell technology has enhanced the precision of organoid studies, offering deeper insights into tumor heterogeneity and treatment response, thereby contributing to the development of personalized treatment approaches. This review outlines the evolution of colorectal cancer organoid technology and highlights its strengths in modeling colorectal malignancies. This review also summarizes the progress made in precision tumor medicine and addresses the challenges in organoid research, particularly when organoid research is combined with single-cell technology. Furthermore, this review explores the future potential of organoid technology in the standardization of culture techniques, high-throughput screening applications, and single-cell multi-omics integration, offering novel directions for future colorectal cancer research.

Early detection of sugarcane diseases is important for effective management strategy. However, it is a challenging task as many diseases can hardly be detected in the early stage of infection due to a lack of human-eye-detectable symptoms. For enhanced detection, hyperspectral imaging technologies can capture light from a broad spectral range which often includes part of the invisible spectral range (e.g., near-infrared), and thereby can potentially capture the features for early detection of sugarcane diseases before the development of visible symptoms. Moreover, deep neural networks are well-developed frameworks from the field of deep learning that can automatically extract features for association with specific disease-related spectra. In this research, early detection of sugarcane smut and sugarcane mosaic diseases was achieved using a combined hyperspectral imaging and deep learning approach that was subsequently applied to track disease development over a five-month trial period. Additionally, the first large-scale high-resolution hyperspectral image dataset of inoculated and healthy (control) sugarcane plants was created and released. Subsequently, experimental results indicated that hyperspectral images containing features that can be used for the early detection of the two target sugarcane diseases were extracted by deep neural network models efficiently. The detection accuracy for both diseases was above 90 % before the appearance of visible symptoms.

Traditional imaging methods have limitations in the diagnosis of peripheral lung lesions. The aim of this study is to evaluate the diagnostic value of the distance measurement method based on ultrasound image-based inverted electrostrain (rEBUS) combined with thoracoscopic lung biopsy (TBLB) for peripheral lung lesions. A group of patients with peripheral lung lesions were recruited for the study, and rEBUS examination was performed simultaneously during TBLB. Using rEBUS ultrasound images combined with electrostrain information, evaluate the morphological characteristics of peripheral lung lesions and the elastic properties of internal tissues. By comparing with pathological examination results, both rEBUS-D-TBLB and rEBUS-GS-TBLB have a higher positive diagnostic rate for PPL under bronchoscopy. However, rEBUS-D-TBLB is more effective in diagnosing benign PPL with ≥ 3 cm PPL than rEBUS-GS-TBLB. The rEBUS-TBLB combined ranging method has shown high accuracy and sensitivity in diagnosing peripheral lung lesions. Ultrasound images provide clear morphological features of the tumor, while the electrical strain information of rEBUS provides elastic information of the internal tissue of the tumor, further improving the accuracy of diagnosis.

Machine learning has been widely applied in well logging formation evaluation studies. However, several challenges negatively impacted the generalization capabilities of machine learning models in practical implementations, such as the mismatch of data domain between training and testing datasets, imbalances among sample categories, and inadequate representation of data model. These issues have led to substantial insufficient identification for reservoir and significant deviations in subsequent evaluations. To improve the transferability of machine learning models within limited sample sets, this study proposes a weight transfer learning framework based on the similarity of the labels. The similarity weighting method includes both hard weights and soft weights. By evaluating the similarity between test and training sets of logging data, the similarity results are used to estimate the weights of training samples, thereby optimizing the model learning process. We develop a double experts' network and a bidirectional gated neural network based on hierarchical attention and multi-head attention (BiGRU-MHSA) for well logs reconstruction and lithofacies classification tasks. Oil field data results for the shale strata in the Gulong area of the Songliao Basin of China indicate that the double experts’ network model performs well in curve reconstruction tasks. However, it may not be effective in lithofacies classification tasks, while BiGRU-MHSA performs well in that area. In the study of constructing large-scale well logging processing and formation interpretation models, it is maybe more beneficial by employing different expert models for combined evaluations. In addition, although the improvement is limited, hard or soft weighting methods is better than unweighted (i.e., average-weighted) in significantly different adjacent wells. The code and data are open and available for subsequent studies on other lithofacies layers.

Multi-channel neural electrodes as a crucial means are of great significance for information exchange between the brain and computers. Herein, we present a 16-channel Si-based active neural probe system that achieves a monolithic integration between the electrodes and circuits in a single probe, making it a standalone integrated electrophysiology recording system. The ASIC prepared on a base (2×2mm2) is a 16-channel analog frontend (AFE) for neural recording, and each channel has a low-noise amplifier (LNA), a bandpass filter (BPF), a buffer and a current bias circuit. The 258 neural signal recording electrodes (22×24μm2) are densely packed on a 50 μm thick, 100 μm wide, and 3 mm long shank. The ASIC of neural probe, internal interconnecting wires are all implemented in commercial SMIC 0.18 μm CMOS technology. The neural probe system achieves a 3.6 μVrms input-referred noise (IRN) in a bandwidth of 1.1Hz-10 kHz, 70.8 μW power consumption, 0.0785 mm2 area per channel, as well as an AFE gain of 58.1 dB Furthermore, the impedances of the Au electrodes can be obtained as 0.5–2.1 MΩ at a frequency of 1 kHz. The functionality of a 16-channel silicon-based neural probe is validated in an in-vivo experiment on lab rats.

Flexible pressure sensors capable of detecting normal and tangential forces through physical contact have garnered considerable interest in the realm of human-interactive systems. However, simultaneous detection of multi-directional forces is still a challenge for current research. Herein, a capacitive flexible pressure sensor based on a sandwich structure for three-dimensional force detection is proposed. The fabrication process of the sensor array is straightforward, capable of effectively distinguishing between normal and tangential forces. Polyimide (PI) serves as the flexible substrate for depositing the metal electrode pattern, while Polydimethylsiloxane (PDMS) acts as the intermediate dielectric layer material and the three-dimensional force conduction block. Through a comparative study of the thickness of the hollow dielectric layer, a pressure sensor with superior performance was prepared, featuring high sensitivity across a wide working range. Test results demonstrate its capability to detect normal forces ranging from 0 to 46 N (0–520 kPa) with a sensitivity of 0.442 N−1 (0.031 kPa−1) and tangential forces from 0 to 10 N with a sensitivity of 0.08 N−1 (X-axis) and 0.07 N−1 (Y-axis). The designed acquisition system can simultaneously gather data from 6 sensor arrays, totaling 240 channels, with a response time of 11 ms. This sensor array, characterized by flexibility, versatility, and a wide range, is suitable for applications in robot tactile perception.

Abstract The primary cilium behaves as a platform for sensing and integrating extracellular cues to control a plethora of cellular activities. However, the functional interaction of this sensory organelle with epithelial-mesenchymal transition (EMT) during pulmonary fibrosis remains unclear. Here, we reveal a critical role for cylindromatosis (CYLD) in reciprocally linking the EMT program and ciliary homeostasis during pulmonary fibrosis. A close correlation between the EMT program and primary cilia is observed in bleomycin-induced pulmonary fibrosis as well as TGF-β-induced EMT model. Mechanistic study reveals that downregulation of CYLD underlies the crosstalk between EMT and ciliary homeostasis by inactivating histone deacetylase 6 (HDAC6) during pulmonary fibrosis. Moreover, manipulation of primary cilia is an effective means to modulate the EMT program. Collectively, these results identify a pivotal role for the CYLD/HDAC6 signaling in regulating the reciprocal interplay between the EMT program and ciliary homeostasis during pulmonary fibrosis.

Abstract Macrophages are multifunctional innate immune cells that play indispensable roles in homeostasis, tissue repair, and immune regulation. However, dysregulated activation of macrophages is implicated in the pathogenesis of various human disorders, making them a potential target for treatment. Through the expression of pattern recognition and scavenger receptors, macrophages exhibit selective uptake of pathogens and apoptotic cells. Consequently, the utilization of drug carriers that mimic pathogenic or apoptotic signals shows potential for targeted delivery to macrophages. In this study, a series of mannosylated or/and phosphatidylserine (PS) -presenting liposomes were developed to target macrophages via the design of experiment (DoE) strategy and the trial-and-error (TaE) approach. The optimal molar ratio for the liposome formulation was DOPC: DSPS: Chol: PEG-PE = 20:60:20:2 based on the results of cellular uptake and cytotoxicity evaluation on RAW 264.7 and THP-1 in vitro. Results from in vivo distribution showed that, in the DSS-induced colitis model and collagen II-induced rheumatoid arthritis model, PS-presenting liposomes (PS-Lipo) showed the highest accumulation in intestine and paws respectively, which holds promising potential for macrophage target therapy since macrophages are abundant at inflammatory sites and contribute to the progression of corresponding diseases. Organs such as the heart, liver, spleen, lung, and kidney did not exhibit histological alterations such as inflammation or necrosis when exposed to PC-presenting liposomes (PC-Lipo) or PS-Lipo. In addition, liposomes demonstrated hemobiocompatibility and no toxicity to liver or kidney for circulation and did not induce metabolic injury in the animals. Thus, the well-designed PS-Lipo demonstrated the most potential for macrophage target therapy.

Abstract Osteoporosis (OP) is a disorder of bone remodeling caused by an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Therefore, inhibiting excessive osteoclast activity is one of the promising strategies for treating OP. A major transient receptor potential cation channel, known as transient receptor potential ankyrin 1 (TRPA1), was found to alleviate joint pain and cartilage degeneration in osteoarthritis. However, little research has focused on TRPA1 function in OP. As a result, this study aimed to explore the TRPA1 characteristics and its potential therapeutic function during osteoclastogenesis. The TRPA1 expression gradually increased in the osteoclast differentiation process; however, its suppression with small interfering RNA and an inhibitor (HC030031) significantly controlled the osteoclast count and the expression of osteoclast characteristic genes. Its suppression also inhibited endoplasmic reticulum (ER) stress-related pancreatic ER kinase (PERK) pathways. An ER stress inhibitor (thapsigargin) reversed the down-regulated levels of ER stress and osteoclast differentiation by suppressing TRPA1. Transcriptome sequencing results demonstrated that TRPA1 negatively regulated reactive oxygen species (ROS) and significantly increased the expression of an antioxidant gene, SRXN1. The osteoclast differentiation and the levels of ER stress were enhanced with SRXN1 inhibition. Finally, TRPA1 knockdown targeting macrophages by adeno-associated virus-9 could relieve osteoclast differentiation and osteopenia in ovariectomized mice. In summary, silencing TRPA1 restrained osteoclast differentiation through ROS-mediated down-regulation of ER stress via inhibiting PERK pathways. The study also indicated that TRPA1 might become a prospective treatment target for OP.

Objective To study the distribution and trend of HIV-1 drug resistance mutation in Dalian blood donors between 2011 and 2020. Methods The protease-reverse transcriptase (PR-RT) region was sequenced in Dalian blood donors tested HIV-1 positive between 2011 and 2020. Drug resistance mutation (DRM) rate and level of resistance to selected drugs were analyzed by the Stanford HIV Drug Resistance Database. Results DRM were detected in 17.2% (30/174) of samples, while transmitted drug resistance (TDR) was 5.7% (10/174). Between 2011 and 2020, DRM and TDR rates increased significantly in 2019 and reached their highest levels in 2020 (44.4% and 22.2%, respectively). DRM carriage was associated with people with college degree or above and with local residents (P