MicroRNA-181a Targets GNAI2 and Affects the Proliferation and Induction Ability of Dermal Papilla Cells: The Potential Involvement of the Wnt/ß-Catenin Signaling Pathway.

Wool is generated by hair follicles (HFs), which are crucial in defining the length, diameter, and morphology of wool fibers. However, the regulatory mechanism of HF growth and development remains largely unknown. Dermal papilla cells (DPCs) are a specialized cell type within HFs that play a crucial role in governing the growth and development of HFs. This study aims to investigate the proliferation and induction ability of ovine DPCs to enhance our understanding of the potential regulatory mechanisms underlying ovine HF growth and development. Previous research has demonstrated that microRNA-181a (miR-181a) was differentially expressed in skin tissues with different wool phenotypes, which indicated that miR-181a might play a crucial role in wool morphogenesis. In this study, we revealed that miR-181a inhibited the proliferation and induction ability of ovine DPCs by quantitative Real-time PCR (qRT-PCR), cell counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, and alkaline phosphatase staining. Then, we also confirmed G protein subunit alpha i2 (GNAI2) is a target gene of miR-181a by dual luciferase reporter assay, qRT-PCR, and Western blot, and that it could promote the proliferation and induction ability of ovine DPCs. In addition, GNAI2 could also activate the Wnt/ß-Catenin signaling pathway in ovine DPCs. This study showed that miR-181a can inhibit the proliferation and induction ability of ovine DPCs by targeting GNAI2 through the Wnt/ß-Catenin signaling pathway.

Excessive heavy metal enrichment disturbs liver functions through the gut microbe in the great Himalayan leaf-nosed bat (Hipposideros armiger).

Heavy metal residues in natural ecosystems have emerged as a significant global environmental problem requiring urgent resolution. Because these elements are non-biodegradable, organisms can accumulate excessive levels of heavy metal elements into their tissues. Previous studies suggest that prolonged exposure to heavy metal enrichment poses comprehensive toxicity to various organs in vertebrates. However, few studies have focused on elucidating the molecular mechanism underlying the hepatotoxic effects of heavy metal enrichment in Chiroptera. In this study, 10 Hipposideros armiger individuals were dissected from Yingde City (YD, relatively pollution-free) and Chunwan City (CW, excessive heavy metals emission). Environmental samples were also obtained. To investigate the mechanism of heavy metal toxicity in bat livers, we employed a combination of multi-omics, pathology, and molecular biology methods. Our results revealed significant enrichment of Cd and Pb in the bat livers and food sources in the CW group (P<0.05). Furthermore, prolonged accumulation of heavy metals disrupted hepatic transcription profiles associated with the solute carriers family, the ribosome pathway, ATP usage, and heat shock proteins. Excessive heavy metal enrichment also altered the relative abundance of typical gut microbe taxa significantly (P<0.05), inhibiting tight-junction protein expression. We observed a significant decrease in the levels of superoxide dismutase, glutathione peroxidase, and glutathione (P<0.05), along with elevated reactive oxygen species (ROS) density and malondialdehyde content following excessive heavy metal enrichment. Additionally, hepatic fat accumulation and inflammation injuries were present under conditions of excessive heavy metal enrichment, while the contents of metabolism biomarkers significantly decreased (P<0.05). Consequently, prolonged heavy metal enrichment can induce hepatotoxicity by disturbing the microbes-gut-liver axis and hepatic transcription modes, leading to a decrease in overall metabolic activity in bats. Our study offers strategies for biodiversity conservation and highlights the importance of addressing environmental pollution to raise public awareness.

Integrated Microfluidic-Transistor Sensing System for Multiplexed Detection of Traumatic Brain Injury Biomarkers.

Traumatic brain injury (TBI) is widely recognized as a global public health crisis, affecting millions of people each year, leading to permanent neurologic, emotional, and occupational disability, and highlighting the urgent need for rapid, sensitive, and early assessment. Here, we design a novel and simple lithography-free method for preparing dual-channel graphene-based field-effect transistors (G-FETs) and integrating them with microfluidic channels for simultaneously multiplexed detection of key blood TBI biomarkers: neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP). The G-FET utilizes an ingenious dual-channel electrode array design, where the source is shared between channels and the drains are independent of each other, which is the key to achieving simultaneous output of dual detection signals. At the same time, the microfluidic chip realizes microscale fluidic control and fast sample response time. This integrated detection system shows excellent sensitivity in biological fluids for the TBI biomarkers with detection limits as low as 55.63 fg/mL for NFL and 144.45 fg/mL for GFAP in phosphate-buffered saline (PBS) buffer, respectively. Finally, the clinical sample analysis shows promising performance for TBI detection, with an area under the curve (AUC) of 0.98 for the two biomarkers. And the combined dual-protein assay is also a good predictor of intracranial injury findings on computed tomography (CT) scans (AUC = 0.907). The integrated microfluidic G-FET device with a dual-signal output strategy has important potential for application in clinical practice, providing more comprehensive information for brain injury assessment.

Microscopic internal spermatic-inferior epigastric vein anastomosis for treating left varicocele.

OBJECTIVE: To evaluate the clinical efficacy of microscopic internal spermatic-inferior epigastric vein anastomosis in the treatment of left varicocele and compare it with microscopic spermatic vein ligation for the same condition. METHODS: A retrospective analysis of 74 patients with left varicocele between July 2020 and July 2022 was performed. The patients were divided into two groups based on the surgical method used. Group A consisted of 37 patients who underwent microscopic internal spermatic-inferior epigastric vein anastomosis, while Group B consisted of 37 patients who underwent microscopic spermatic vein ligation. Comparison of preoperative and postoperative semen quality, reproductive hormone levels, scrotal ultrasound results, duration of surgery, length of hospital stay, postoperative recurrence rate, and occurrence of complications with a follow-up time of 12 mo between two groups. RESULTS: Both groups showed significant improvements in semen quality and serum reproductive hormone levels. The Group A demonstrated significantly improved sperm forward motility compared to Group B, but had longer operation times and hospital stays (P < 0.05). After 1 year of follow-up, 8 partners in Group A and 6 partners in Group B achieved natural conception, with no significant difference between the two groups. There were no recurrences observed in either group during the follow-up period, and no significant statistical differences were found in other postoperative observation indicators. CONCLUSIONS: Both microscopic internal spermatic-inferior epigastric vein anastomosis and microscopic spermatic vein ligation are effective surgical methods for treating left varicocele. Anastomosis surgery provides greater improvement in sperm motility, although it is associated with longer operation times and hospital stays.

A portable transistor immunosensor for fast identification of porcine epidemic diarrhea virus.

Widespread distribution of porcine epidemic diarrhea virus (PEDV) has led to catastrophic losses to the global pig farming industry. As a result, there is an urgent need for rapid, sensitive and accurate tests for PEDV to enable timely and effective interventions. In the present study, we develop and validate a floating gate carbon nanotubes field-effect transistor (FG CNT-FET)-based portable immunosensor for rapid identification of PEDV in a sensitive and accurate manner. To improve the affinity, a unique PEDV spike protein-specific monoclonal antibody is prepared by purification, and subsequently modified on FG CNT-FET sensor to recognize PEDV. The developed FET biosensor enables highly sensitive detection (LoD: 8.1 fg/mL and 100.14 TCID50/mL for recombinant spike proteins and PEDV, respectively), as well as satisfactory specificity. Notably, an integrated portable platform consisting of a pluggable FG CNT-FET chip and a portable device can discriminate PEDV positive from negative samples and even identify PEDV and porcine deltacoronavirus within 1 min with 100% accuracy. The portable sensing platform offers the capability to quickly, sensitively and accurately identify PEDV, which further points to a possibility of point of care (POC) applications of large-scale surveillance in pig breeding facilities.

Discovering single cannabidiol or synergistic antitumor effects of cannabidiol and cytokine-induced killer cells on non-small cell lung cancer cells.

Introduction: A multitude of findings from cell cultures and animal studies are available to support the anti-cancer properties of cannabidiol (CBD). Since CBD acts on multiple molecular targets, its clinical adaptation, especially in combination with cancer immunotherapy regimen remains a serious concern. Methods: Considering this, we extensively studied the effect of CBD on the cytokine-induced killer (CIK) cell immunotherapy approach using multiple non-small cell lung cancer (NSCLC) cells harboring diverse genotypes. Results: Our analysis showed that, a) The Transient Receptor Potential Cation Channel Subfamily V Member 2 (TRPV2) channel was intracellularly expressed both in NSCLC cells and CIK cells. b) A synergistic effect of CIK combined with CBD, resulted in a significant increase in tumor lysis and Interferon gamma (IFN-g) production. c) CBD had a preference to elevate the CD25+CD69+ population and the CD62L_CD45RA+terminal effector memory (EMRA) population in NKT-CIK cells, suggesting early-stage activation and effector memory differentiation in CD3+CD56+ CIK cells. Of interest, we observed that CBD enhanced the calcium influx, which was mediated by the TRPV2 channel and elevated phosphor-Extracellular signal-Regulated Kinase (p-ERK) expression directly in CIK cells, whereas ERK selective inhibitor FR180204 inhibited the increasing cytotoxic CIK ability induced by CBD. Further examinations revealed that CBD induced DNA double-strand breaks via upregulation of histone H2AX phosphorylation in NSCLC cells and the migration and invasion ability of NSCLC cells suppressed by CBD were rescued using the TRPV2 antagonist (Tranilast) in the absence of CIK cells. We further investigated the epigenetic effects of this synergy and found that adding CBD to CIK cells decreased the Long Interspersed Nuclear Element-1 (LINE-1) mRNA expression and the global DNA methylation level in NSCLC cells carrying KRAS mutation. We further investigated the epigenetic effects of this synergy and found that adding CBD to CIK cells decreased the Long Interspersed Nuclear Element-1 (LINE-1) mRNA expression and the global DNA methylation level in NSCLC cells carrying KRAS mutation. Conclusions: Taken together, CBD holds a great potential for treating NSCLC with CIK cell immunotherapy. In addition, we utilized NSCLC with different driver mutations to investigate the efficacy of CBD. Our findings might provide evidence for CBD-personized treatment with NSCLC patients.

Cell-penetrating peptides noncovalently modified red phosphorescent nanoparticles for high-efficiency imaging.

The application of long-lived phosphorescence probes in time-resolved luminescence imaging is limited by their low quantum yield in aqueous solutions. However, sensitization of thermally activated delayed fluorescence (TADF) materials can compensate for this limitation while addressing the issue of insufficient proportion of their own long lifetime. In this study, we utilized the characteristics of phosphorescence and TADF materials simultaneously by doping the receptor iridium complex PMD-Ir into the donor TADF polymer PCzDP-20 through donor-receptor doping method, and successfully prepared highly efficient red phosphorescent nanoparticles. The quantum yield of the nanoparticles obtained by this method reaches up to 30%, and the luminescence lifetime can reach several thousand nanoseconds. Additionally, due to the low concentration doping of PMD-Ir, the risk of transition metal toxicity is greatly reduced. Furthermore, we used non-covalent modification with amphiphilic cell-penetrating peptides (CPPs) to increase the cell membrane permeability of the nanoparticles. The CPPs modified nanoparticles achieve in vivo confocal imaging of zebrafish and intracellular time-resolved imaging by its significantly improved bioimaging capabilities. The functional nanoparticles designing method fully utilizes the characteristics of PMD-Ir, PCzDP-20, and CPPs, solving the problems of low quantum yield and poor membrane permeability of Ir-complex nanoparticles. This will greatly promote the development of time-resolved luminescence imaging.

Evolving insights into the improvement of adoptive T-cell immunotherapy through PD-1/PD-L1 blockade in the clinical spectrum of lung cancer.

Undeniably, cancer immunotherapies have expanded the spectrum of cancer treatment, however, some patients do not respond to immunotherapies. This scenario is no different for lung cancer, whose two main types, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), still pose a serious clinical challenge. Adoptive T-cell therapies (ATC), which primarily include cytokine-induced killer (CIK) cell therapy, chimeric antigen receptor T-cell (CAR T-cell) therapy and γδ-T-cell therapy, strengthen the patient's immune system in combating cancer. Combining ATC with immune checkpoint inhibitors (ICI) further enhances the effectiveness of this approach to eradicate cancer. With a particular emphasis on CIK cell therapy, which recently completed 30 years, we highlight the role of the PD-1/PD-L1 axis in NSCLC and SCLC. Besides, we provide insights into the potential synergies of PD-1/PD-L1 inhibitors with adoptive T-cell immunotherapy in reshaping the treatment paradigm for lung cancer.

Exploring the relationship among soccer-related knowledge, attitude, practice, and self-health in Chinese campus soccer education.

China has promoted campus soccer for over a decade due to its potential health benefits. The study aimed to explore soccer knowledge (SK), soccer attitude (SA), soccer practice (SP), and health status among Chinese freshmen and sophomore undergraduates who had received campus soccer education. Of the 7419 participants, 1,069 were valid and included in the analysis. Structural equation modeling (SEM) results indicated SK is positively associated with SA (p < 0.001), but negatively with SP (p < 0.01). SA was positively linked to SP (p < 0.001). SK indirectly affected SP through SA (Z = 13.677). Random forest-tree-structured Parzen estimators (RF-TPE) with SHAP indicated SP holds primary importance with a strong negative impact on health. Additionally, differences in rankings for SK, SA, and SP were observed among gender and urban-rural groups. These results reveal current campus soccer education is suboptimal to health promotion.

FecB Was Associated with Litter Size and Follows Mendel's Laws of Inheritance When It Transited to Next Generation in Suhu Meat Sheep Breeding Population.

In order to investigate the effect of FecB on litter size and growth and development traits of Suhu meat sheep and the inheritance patterns of FecB between parents and offspring in the population. In this experiment, 2241 sheep from the Suhu meat sheep population were tested for FecB using capillary electrophoresis. We combined the lambing records of 473 ewes, the growth trait records of 881 sheep at both the birth and weaning (2-month-old) stages, and the complete genealogical records of 643 lambs to analysis the distribution of FecB in the Suhu meat sheep breeding population, its effect on litter size of ewes, growth and development of lambs, and the inheritance patterns of FecB. The results showed that there were three genotypes of FecB in the Suhu meat sheep population, namely the AA genotype, AG genotype, and GG genotype. FecB in this population has a moderate polymorphism (0.25 < PIC < 0.5), and deviates from Hardy-Weinberg disequilibrium (p < 0.05). The litter size of GG genotype ewes was significantly higher than that with the AG and AA genotypes (p < 0.01). A Chi-square test showed that the inheritance patterns of FecB follows Mendel's Laws of Inheritance (p > 0.05). An association analysis of different genotypes of FecB with body weight and body size of Suhu meat sheep at birth and weaning revealed that FecB adversely affects the early growth and development of Suhu meat sheep. In summary, FecB can improve the litter size of ewes but it has negative effects on the early growth and survival rate of lambs in sheep. Therefore, FecB test results and feeding management measures should be comprehensively applied to improve the reproductive performance of ewes, the survival rate and production performance of lambs in sheep production, and thus improve the economic benefits of sheep farms.

Surface Lattice Modulation Enables Stable Cycling of High-Loading All-solid-state Batteries at High Voltages.

Halide solid electrolytes, known for their high ionic conductivity at room temperature and good oxidative stability, face notable challenges in all-solid-state Li-ion batteries (ASSBs), especially with unstable cathode/solid electrolyte (SE) interface and increasing interfacial resistance during cycling. In this work, we have developed an Al3+-doped, cation-disordered epitaxial nanolayer on the LiCoO2 surface by reacting it with an artificially constructed AlPO4 nanoshell; this lithium-deficient layer featuring a rock-salt-like phase effectively suppresses oxidative decomposition of Li3InCl6 electrolyte and stabilizes the cathode/SE interface at 4.5 V. The ASSBs with the halide electrolyte Li3InCl6 and a high-loading LiCoO2 cathode demonstrated high discharge capacity and long cycling life from 3 to 4.5 V. Our findings emphasize the importance of specialized cathode surface modification in preventing SE degradation and achieving stable cycling of halide-based ASSBs at high voltages.

Velvet antler polypeptide (VAP) protects against cerebral ischemic injury through NF-κB signaling pathway in vitro.

OBJECTIVE: Velvet antler polypeptide (VAP) has been shown to play important roles in the immune and nervous systems. The purpose of this study was to investigate the protective effects of VAP on cerebral ischemic injury with the involvement of NF-κB signaling pathway in vitro. MATERIALS AND METHODS: PC-12 cells stimulated by oxygen-glucose deprivation/reperfusion (OGD/R) was used to mimic cerebral ischemic injury in vitro. The levels of ROS, SOD, and intracellular concentrations of Ca2+ were measured by the relevant kits. Meanwhile, the expressions of inflammatory cytokines (IL-6, IL-1ß, and TNF-α) were determined by ELISA kit assay. In addition, MTT, EdU, and flow cytometry assays were used to measure the cell proliferation and apoptosis. Besides which, the related proteins of NF-κB signaling pathway were measured by western blotting assay. RESULTS: VAP alleviated cerebral ischemic injury by reducing OGD/R-induced oxidative stress, inflammation, and apoptosis in PC-12 cells in a time dependent manner. Mechanistically, VAP inhibited the levels of p-p65 and p-IkB-α in a time dependent manner, which was induced by OGD/R operation. Moreover, NF-κB agonist diprovocim overturned the suppression effects of VAP on OGD/R-induced oxidative stress, inflammation, and apoptosis in PC-12 cells. CONCLUSIONS: The results demonstrate that VAP may alleviate cerebral ischemic injury by suppressing the activation of NF-κB signaling pathway.

SP1 and KROX20 Regulate the Proliferation of Dermal Papilla Cells and Target the CUX1 Gene.

Previous studies have demonstrated that CUX1 could contribute to the proliferation of DPCs in vitro, but the upstream transcriptional regulatory mechanisms of CUX1 remain largely unknown. This study aimed to investigate the upstream transcriptional regulators of CUX1 to enhance our comprehension of the mechanism of action of the CUX1 gene in ovine DPCs. Initially, the JASPAR (2024) software was used to predict the upstream target transcription factors for the CUX1 gene. Subsequently, through RT-qPCR and a double luciferase reporter assay, the interaction between SP1, KROX20, and CUX1 was established, respectively. The results indicated that SP1 and KROX20 were two highly reliable upstream transcription regulators for the CUX1 gene. Additionally, we found that SP1 promoted the proliferation of DPCs by overexpressing SP1 in DPCs, and KROX20 inhibited the proliferation of DPCs by overexpressing KROX20 in DPCs. These findings are also consistent with the transcriptional regulation of CUX1 by SP1 and KROX20, respectively. This study suggests that the effect of DPC proliferation in vitro by CUX1 may regulated by the transcription factors SP1 and KROX20.

Adult-onset congenital intestinal malrotation: A case report and literature review.

BACKGROUND: Intestinal malrotation is an infrequent congenital anomaly primarily observed in neonates, and adult-onset cases are exceedingly rare. Studies on adult congenital intestinal malrotation are limited. METHODS: A case with congenital intestinal malrotation is reported in our study. The clinical data were collected and the treatment process and effect were evaluated. RESULTS: A 45-year-old female who had been experiencing vomiting for over 40 years was admitted to our hospital. According to the result of CT scan, intestinal volvulus accompanied by bowel obstruction was suspected. Then laparoscopic examination was applied to the patient and was ultimately diagnosed with adult congenital intestinal malrotation. We performed Ladd's procedure combined with gastrojejunostomy and Braun anastomosis. The patient recovered well and was successfully discharged from the hospital on the 13th day after surgery. After a 6-month follow-up, the symptom of vomiting was significantly alleviated and body weight was gained for 10 kg. She was very satisfied with the treatment. CONCLUSION: Adult congenital intestinal malrotation is a rare disease that is often misdiagnosed owing to nonspecific clinical manifestations. Therefore, awareness about this condition should be enhanced. Surgery remains the cornerstone of treatment for this disease. Combining gastrojejunostomy and Braun anastomosis with the traditional Ladd procedure can optimize surgical outcomes.

Experimental Decoding and Tuning Electronic Friction of Si Nanotip Sliding on Graphene.

Due to the coupled contributions of adhesion and carrier to friction typically found in previous research, decoupling the electron-based dissipation is a long-standing challenge in tribology. In this study, by designing and integrating a graphene/h-BN/graphene/h-BN stacking device into an atomic force microscopy, the carrier density dependent frictional behavior of a single-asperity sliding on graphene is unambiguously revealed by applying an external back-gate voltage, while maintaining the adhesion unaffected. Our experiments reveal that friction on the graphene increases monotonically with the increase of carrier density. By adjusting the back-gate voltage, the carrier density of the top graphene layer can be tuned from -3.9 × 1012 to 3.5 × 1012 cm-2, resulting in a ∼28% increase in friction. The mechanism is uncovered from the consistent dependence of the charge density redistribution and sliding barrier on the carrier density. These findings offer new perspectives on the fundamental understanding and regulation of friction at van der Waals interfaces.

Significance of Gastrokine-1 Polymorphism Rs4254535 as a Prognostic Marker and its Association with Clinical Characteristics in Chinese Lung Cancer Patients.

Background: The single nucleotide polymorphism (SNP) of Gastrokine-1 (GKN1) is associated with lung cancer but its association with prognosis is not clear. Methods: Genomic DNA was extracted from the blood samples of 888 patients with lung cancer. The association between GKN1 polymorphism rs4254535 and prognostic was analyzed by the Kaplan-Meier (KM) method, Log-rank test, and Cox proportional hazards model. Results: In females and patients diagnosed with late-stage lung cancer, the CC genotype (CC vs TT, adjusted odds ratio [HR] = 0.57, 95% Confidence Interval [CI]: 0.33-0.99, P = 0.045; HR = 0.66, 95% CI: 0.48-0.92, P = 0.014) and recessive CC genotype (CC vs TT + TC, HR = 0.55, 95% CI: 0.32-0.94, P = 0.028; HR = 0.64, 95% CI: 0.47-0.89, P = 0.006) of rs4254535 conferred a better prognosis, compared with the TT and TT + TC genotype. Rs4254535 dominate TC + CC genotype, recessive CC genotype, and C allele who were adenocarcinoma patients had a significantly better prognosis. The recessive CC genotype of non-smoking patients has a better prognosis, compared to the TT + TC genotype. Additionally, in the dominant TT + TC genotype and C allele, no family history patients had a significantly better prognosis, compared to the TT genotype. Conclusion: For lung cancer patients, GKN1 polymorphism rs4254535 may be a protective genetic marker and predicts the prognosis of lung cancer patients.

Metal-Free, Hindered, Regioselective Access to Multifunctional Groups Diarylamines via SN Ar Substitution of P-Nitroso Aromatic Methyl Ether by Arylamines.

Multifunctional groups diarylamines, an innovative product, efficiently produced from arylamines and p-nitrosoanisole derivatives by intermolecular SN Ar under weak acid conditions. This SN Ar proceeds under mild reaction conditions, and more significantly, the substrates involved do not necessarily require strong electron-withdrawing groups. Moreover, this SN Ar is characterized by resistance to space crowding, tolerance to halogen and nitroso functional groups, and high regioselectivity. Mechanistic observations suggest that the SN Ar is the result of the transfer of the positive charge center of the protonated nitroso group to the p-methoxy group.

A novel transcriptomic signature associated with lymphovascular invasion predicts clinical outcomes, tumor microenvironment, and therapeutic response in lung adenocarcinoma.

PURPOSE: Since TNM staging has limitations for predicting post-operative outcomes and relapse, more effective prediction tools need to be researched and developed. Lymphovascular invasion, LVI, as a histopathological feature, has been widely shown to have a correlation with poor prognosis and early recurrence of lung adenocarcinoma (LUAD). However, LVI assessment is limited by subjective bias, and therefore its efficacy in practical clinical application needs further clarification. The aim of this study was to formulate a new signature based on LVI-related genes to predict prognosis and recurrence in patients with lung adenocarcinoma. METHODS: Clinicopathological information, gene sequencing data and whole slide images (WSIs) of LUAD patients were downloaded from the Cancer Genome Atlas (TCGA) databases. LVI statue were evaluated by professional pathologists, and then the differentially expressed genes (LVI DEGs) associated with LVI were screened. The least absolute shrinkage and selection operator (LASSO) and Step Cox regression models were used to construct LVI-associated risk scores (LVRS), including PAQR4, ARGHEF6, CKS1B, CFTR and SEC14L4. The validity of the LVRS score was evaluated on multiple external datasets and our JSSZL cohort dataset. Using LVRS scores and clinical information, nomogram were constructed for use by clinicians. In addition, we further explored the relationship between LVRS score and clinicopathological features, immune infiltration, tumor mutational load, and immunotherapy response, and confirmed the expression of key genes in LVRS score in lung adenocarcinoma tissues using qRT-PCR and immunohistochemistry (IHC) techniques. RESULTS: Based on the LVRS, patients could be classified into high-LVRS and low-LVRS groups. It was found that OS and PFS were significantly worse in the high-LVRS group than in the low-LVRS group (p < 0.001). By ROC curve analysis, it could be found that the nomogram combining LVRS and clinical information could accurately predict the prognosis of LUAD patients with the area under the curve of 1,3,5-year survival rate could reach 0.754, 0.741 and 0.735. The results of univariate and multivariate analysis showed that LVRS was an independent prognostic factor. At the same time, there were significant differences in the mutation profiles and immune microenvironment between the high-LVRS and low-LVRS groups, with the high-LVRS group having a significantly higher mutation rate than the low-LVRS group and exhibiting immunological "cold" features. By the experimental results, higher expression levels of PAQR4 and CKS1B were found in LUAD tissues, while lower expression levels of ARGHEF6, CFTR and SEC14L4 were observed. CONCLUSIONS: The LVRS established in this study serves as a valid tool to predict the prognosis and recurrence status of lung adenocarcinoma patients and has a predictive effect on the response to postoperative treatment. The establishment of LVRS may offer some theoretical support to clinical treatment strategies for patients with lung adenocarcinoma following surgical intervention.

Plug-and-play smart transistor bio-chips implementing point-of-care diagnosis of AMI with modified CRISPR/Cas12a system.

The point-of-care diagnosis of acute myocardial infarction (AMI), an extremely lethal disease with only a few hours of golden rescue time, is significant and urgently required. Here, we describe a plug-and-play carbon nanotube field effect transistor (CNT-FET) bio-chip supported with a smart portable readout for ultrasensitive and on-site testing of cardiac troponin I (cTnI), which is one of the most specific and valuable biomarkers of AMI. A modified clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system, featuring the G-triplex structured reporter, was first combined with the CNT-FET to realize non-nucleic acid detection. Such a unique CNT-FET biosensor achieved the high sensitivity (LOD: 0.33 fg/mL), which is expected to give timely warning in the early stage of myocardial injury. In addition, a bilayer gate dielectric consisting of Y2O3/HfO2, employed into the passivation process, enabled the high environmental stability and repeatability of CNT-FET. More importantly, the homemade compact chip readout forged a field-deployable cTnI analytical tool, realizing "plasma-to-answer" performance for AMI patients in point-of-care testing scenarios. The developed technology holds promise to help doctors make clinical decisions faster, especially in remote areas.

SOX18 Promotes the Proliferation of Dermal Papilla Cells via the Wnt/ß-Catenin Signaling Pathway.

SRY-box transcription factor 18 (SOX18) is known to play a crucial role in the growth and development of hair follicles (HF) in both humans and mice. However, the specific effect of SOX18 on sheep hair follicles remains largely unknown. In our previous study, we observed that SOX18 was specifically expressed within dermal papilla cells (DPCs) in ovine hair follicles, leading us to investigate its potential role in the growth of hair follicles in sheep. In the present study, we aimed to examine the effect of SOX18 in DPCs and preliminarily study its regulatory mechanism through RNA-seq. We initially found that the overexpression of SOX18 promoted the proliferation of DPCs compared to the negative control group, while the interference of SOX18 had the opposite effect. To gain further insight into the regulatory mechanism of SOX18, we conducted RNA-seq analysis after knocking down SOX18 in Hu sheep DPCs. The result showed that the Wnt/ß-Catenin signaling pathway was involved in the growth process of DPC after SOX18 knockdown. Subsequently, we investigated the effect of SOX18 on the Wnt/ß-Catenin signaling pathway in DPCs using TOP/FOP-flash, qRT-PCR, and Western blot (WB) analysis. Our data demonstrated that SOX18 could activate the Wnt/ß-Catenin signaling pathway in DPCs. Additionally, we observed that SOX18 could rescue the proliferation of DPCs after inhibiting the Wnt/ß-Catenin signaling pathway. These findings underscore the essential role of SOX18 as a functional molecule governing the proliferation of DPCs. Additionally, these findings also greatly enhance our understanding of the role of SOX18 in the proliferation of DPCs and the growth of wool in Hu sheep.