Effect of Targeted Nursing Combined with Psychological Intervention on Chemotherapy for Gastric Carcinoma and its Influence on Patient Compliance.

Objective: To explore and analyze the effect of targeted nursing combined with psychological intervention on chemotherapy for gastric carcinoma and its influence on patient compliance. Methods: The study subjects were 88 patients diagnosed with gastric cancer and treated with chemotherapy from December 2019 to May 2021. Results: The Self-Rating Anxiety Scale and Hamilton Depression Cale scores of the study group were significantly lower than those of the control group (33.45±6.11 vs. 44.17±5.76; 35.14±5.44 vs. 46.87±5.23, respectively; P < .05); In the Morisky scale, patients in the study group scored higher than those in the control group in terms of weight control, medication compliance, appropriate exercise, and diet control; the study group had more cases of Grade 0 nausea and vomiting and significantly fewer cases of Grades I, II, III, and IV nausea and vomiting than the control group compliance (P < .05); patients in the study group gave higher scores than those in the control group on the nursing care quality, from the aspects of the quality of nursing staff. These findings highlight the significant improvements in psychological well-being, adherence to health-related behaviors, reduced nausea and vomiting, and overall satisfaction with nursing care in patients receiving targeted nursing and psychological intervention. Conclusion: The utilization of targeted nursing in tandem with psychological counseling has demonstrated a notably positive impact on chemotherapy outcomes for stomach malignancy. The amalgamation of targeted nursing and psychological intervention not only enhances patient compliance during gastric carcinoma chemotherapy but also leads to a reduction in negative emotions, decreased instances of nausea and vomiting, and higher scores for nursing quality. These findings have significant implications for clinical practice, suggesting that the integration of targeted nursing and psychological support could be a valuable approach in optimizing patient care for gastric carcinoma. The observed improvements underscore the potential for widespread adoption of this combined intervention strategy in clinical settings, potentially leading to enhanced treatment outcomes and overall patient well-being.

Relationship of long-term exposure to air pollutant mixture with metabolic-associated fatty liver disease and subtypes: A retrospective cohort study of the employed population of Southwest China.

BACKGROUND: While evidence suggests that PM2.5 is associated with overall prevalence of Metabolic (dysfunction)-Associated Fatty Liver Disease (MAFLD), effects of comprehensive air pollutant mixture on MAFLD and its subtypes remain unclear. OBJECTIVE: To investigate individual and joint effects of long-term exposure to comprehensive air pollutant mixture on MAFLD and its subtypes. METHODS: Data of 27,699 participants of the Chinese Cohort of Working Adults were analyzed. MAFLD and subtypes, including overweight/obesity, lean, and diabetes MAFLD, were diagnosed according to clinical guidelines. Concentrations of NO3-, SO42-, NH4+, organic matter (OM), black carbon (BC), PM2.5, SO2, NO2, O3 and CO were estimated as a weighted average over participants' residential and work addresses for the three years preceding outcome assessment. Logistic regression and weighted quantile sum regression were used to estimate individual and joint effects of air pollutant mixture on presence of MAFLD. RESULTS: Overall prevalence of MAFLD was 26.6 % with overweight/obesity, lean, and diabetes MAFLD accounting for 92.0 %, 6.4 %, and 1.6 %, respectively. Exposure to SO42-, NO3-, NH4+, BC, PM2.5, NO2, O3and CO was significantly associated with overall MAFLD, overweight/obesity MAFLD, or lean MAFLD in single pollutant models. Joint effects of air pollutant mixture were observed for overall MAFLD (OR = 1.10 [95 % CI: 1.03, 1.17]), overweight/obesity (1.09 [1.02, 1.15]), and lean MAFLD (1.63 [1.28, 2.07]). Contributions of individual air pollutants to joint effects were dominated by CO in overall and overweight/obesity MAFLD (Weights were 42.31 % and 45.87 %, respectively), while SO42- (36.34 %), SO2 (21.00 %) and BC (12.38 %) were more important in lean MAFLD. Being male, aged above 45 years and smoking increased joint effects of air pollutant mixture on overall MAFLD. CONCLUSIONS: Air pollutant mixture was associated with MAFLD, particularly the lean MAFLD subtype. CO played a pivotal role in both overall and overweight/obesity MAFLD, whereas SO42- were associated with lean MAFLD.

HHLA2 deficiency inhibits pancreatic cancer progression and THP-1 macrophage M2 polarization via EGFR/MAPK/ERK and mTOR/AKT pathway.

BACKGROUND: Human endogenous retrovirus subfamily H long terminal repeat associating protein 2, (HHLA2), a member of B7 family, exhibits heightened expression in various malignant tumors. However, the exact functions of HHLA2 in pancreatic cancer (PC) remain incompletely elucidated. METHODS: We initially conducted an analysis of the B7 family members' expression pattern in pancreatic tumor samples and adjacent normal tissues using The Cancer Genome Atlas (TCGA) database. Subsequently, immunohistochemistry, RT-qPCR and western blot methods were used to assess HHLA2 expression levels in PC tissues and cell lines. Furthermore, after silencing HHLA2 in PC cell lines, cell migration and proliferation of PC cells were detected by wound healing and CCK-8 assays, and cell invasion of PC cells was detected by transwell assays. We also investigated the regulation of epithelial-mesenchymal transition (EMT) markers and levels of EGFR, MEK, ERK1/2, mTOR and AKT via western blot analysis. Finally, the correlation between HHLA2 expression and immune infiltration was further explored. RESULTS: Silencing of HHLA2 resulted in the inhibition of PC cell proliferation, migration and invasion, potentially through the suppression of the EGFR/MAPK/ERK and mTOR/AKT signaling pathway. Additionally, silencing HHLA2 led to the inhibition of M2-type polarization of tumor associated macrophages (TAMs). CONCLUSION: The knockdown of HHLA2 was observed to inhibit the migration and invasion of PC cells through the regulation of the EMT process and EGFR/MAPK/ERK and mTOR/AKT pathway. Furthermore, silencing HHLA2 was found to modulate M2 polarization of TAMs. These finding suggest that HHLA2 could be a promising therapeutic target for Pancreatic cancer.

A PSMA PET/CT-based risk model for prediction of concordance between targeted biopsy and combined biopsy in detecting prostate cancer.

PURPOSE: This study is to investigate the diagnostic value of 68Ga-PSMA-11 in improving the concordance between mpMRI-TB and combined biopsy (CB) in detecting PCa. METHODS: 115 consecutive men with 68Ga-PSMA-11 PET/CT prior to prostate biopsy were included for analysis. PSMA intensity, quantified as maximum standard uptake value (SUVmax), minimum apparent diffusion coefficient (ADCmin) and other clinical characteristics were evaluated relative to biopsy concordance using univariate and multivariate logistic regression analyses. A prediction model was developed based on the identified parameters, and a dynamic online diagnostic nomogram was constructed, with its discrimination evaluated through the area under the ROC curve (AUC) and consistency assessed using calibration plots. To assess its clinical applicability, a decision curve analysis (DCA) was performed, while internal validation was conducted using bootstrapping methods. RESULTS: Concordance between mpMRI-TB and CB occurred in 76.5% (88/115) of the patients. Multivariate logistic regression analyses performed that SUVmax (OR= 0.952; 95% CI 0.917-0.988; P= 0.010) and ADCmin (OR= 1.006; 95% CI 1.003-1.010; P= 0.001) were independent risk factors for biopsy concordance. The developed model showed a sensitivity, specificity, accuracy and AUC of 0.67, 0.78, 0.81 and 0.78 in the full sample. The calibration curve demonstrated that the nomogram's predicted outcomes closely resembled the ideal curve, indicating consistency between predicted and actual outcomes. Furthermore, the decision curve analysis (DCA) highlighted the clinical net benefit achievable across various risk thresholds. These findings were reinforced by internal validation. CONCLUSIONS: The developed prediction model based on SUVmax and ADCmin showed practical value in guiding the optimization of prostate biopsy pattern. Lower SUVmax and Higher ADCmin values are associated with greater confidence in implementing mono-TB and safely avoiding SB, effectively balancing benefits and risks.

Steric Control of Luminescence in Phenyl-Substituted Trityl Radicals.

Triphenylmethyl (trityl) radicals have shown potential for use in organic optoelectronic applications, but the design of practical trityl structures has been limited to donor/radical charge-transfer systems due to the poor luminescence of alternant symmetry hydrocarbons. Here, we circumvent the symmetry-forbidden transition of alternant hydrocarbons via excited-state symmetry breaking in a series of phenyl-substituted tris(2,4,6-trichlorophenyl)methyl (TTM) radicals. We show that 3-fold phenyl substitution enhances the emission of the TTM radical and that steric control modulates the optical properties in these systems. Simple ortho-methylphenyl substitution boosts the photoluminescence quantum efficiency from 1% (for TTM) to 65% at a peak wavelength of 612 nm (for 2-T3TTM) in solution. In the crystalline solid state, the neat 2-T3TTM radical shows a remarkably high photoluminescence quantum efficiency of 25% for emission peaking at 706 nm. This has implications in the design of aryl-substituted radical structures where the electronic coupling of the substituents influences variables such as emission, charge transfer, and spin interaction.

Changes of PK/PD of Meropenem in patients with abdominal septic shock and exploration of clinical rational administration plan: a prospective exploratory study.

This study aimed to explore the changes of pharmacokinetic parameters after meropenem in patients with abdominal septic shock after gastrointestinal perforation, and to simulate the probability of different dosing regimens achieving different pharmacodynamic goals. The study included 12 patients, and utilized high performance liquid chromatography-tandem mass spectrometry to monitor the plasma concentration of meropenem. The probability of target attainment (PTA) for different minimum inhibitory concentration (MIC) values and %fT > 4MIC was compared among simulated dosing regimens. The results showed that in 96 blood samples from 12 patients, the clearance (CL) of meropenem in the normal and abnormal creatinine clearance subgroups were 7.7 ± 1.8 and 4.4 ± 1.1 L/h, respectively, and the apparent volume of distribution (Vd) was 22.6 ± 5.1 and 17.2 ± 5.8 L, respectively. 2. Regardless of the subgroup, 0.5 g/q6h infusion over 6 h regimen achieved a PTA > 90% when MIC ≤ 0.5 mg/L. 1.0 g/q6h infusion regimen compared with other regimen, in most cases, the probability of making PTA > 90% is higher. For patients at low MIC, 0.5 g/q6h infusion over 6 h may be preferable. For patients at high MIC, a dose regimen of 1.0 g/q6 h infusion over 6 h may be preferable. Further research is needed to confirm this exploratory result.

Anti-Solvent-Free Fabrication of Stable FA0.9Cs0.1PbI3 Perovskite Solar Cells with Efficiency Exceeding 24.0% through a Naphthalene-Based Passivator.

The anti-solvent-free fabrication of high-efficiency perovskite solar cells (PSCs) holds immense significance for the transition from laboratory-scale to large-scale commercial applications. However, the device performance is severely hindered by the increased occurrence of surface defects resulting from the lack of control over nucleation and crystallization of perovskite using anti-solvent methods. In this study, 2-(naphthalen-2-yl)ethylamine hydriodide (NEAI) is employed as the surface passivator for perovskite films without using any anti-solvent. Naphthalene demonstrates strong π-π conjugation, which aids in the efficient extraction of charge carriers. Additionally, the naphthalene-ring moieties form a tight attachment to the perovskite surface. After NEAI treatment, FA and I vacancies are selectively occupied by NEA+ and I- in NEAI respectively, thus effectively passivating the surface defects and isolating the surface from moisture. Ultimately, the optimized NEAI-treated device achieves a promising power conversion efficiency (PCE) of 24.19% (with a certified efficiency of 23.94%), featuring a high fill factor of 83.53%. It stands out as one of the reported high PCEs achieved for PSCs using the spin-coating technique without the need for any anti-solvent so far. Furthermore, the NEAI-treated device can maintain ≈87% of its initial PCE after 2000 h in ambient air with a relative humidity of 30% ± 5%.

Protective effect of resveratrol on nickel-refining fumes-induced inflammatory damage.

Nickel (Ni), a ductile and hard silver-white transition metal, is commonly found in occupational environments and can harm the human body. Since it is a toxic compound, long-term Ni exposure can cause pneumonia, rhinitis, and other types of respiratory inflammatory diseases. Resveratrol (Res) is a plant antitoxin polyphenol, which also has anti-cancer and anti-inflammatory properties. In this report, the toxicity of Ni-refining fumes on the human lung bronchial epithelial (BEAS-2B) cells, as well as the protective effects of Res were investigated in vitro, and the specific mechanism of its anti-inflammatory effect was explained. The experimental observations of this study revealed that Ni-refining fumes induce BEAS-2B cell damage, increase reactive oxygen species (ROS) content, activate NLRP3 (LRR-, NOD-, and pyrin domain-containing 3) inflammasome, and promote the secretion of the cytokine Interleukin (IL)-1ß, leading to cellular inflammation and reducing cell activity. Resveratrol (20 µmol/L) activated sirtuin 1 (SIRT1) in BEAS-2B cells to increase protein and mRNA expression. SIRT1 was observed to inhibit the transcriptional activity of nuclear factor-kappaB (NF-κB), reduced the expression of NLRP3 protein and mRNA, and inhibited NLRP3 inflammation. The level of inflammasome activation and IL-1ß overexpression could reduce the inflammatory damage caused by the Ni-refining fume particles on the BEAS-2B cells and exert anti-inflammatory protective effects. In vivo experiments further confirmed that resveratrol could effectively alleviate the acute inflammatory injuries caused due to exposure to the Ni-refining fume particles in the lung tissues of the Wistar rats, and verified that resveratrol could exert its anti-inflammatory impact through the SIRT1-NF-κB-NLRP3 pathway. These results provide an important theoretical basis for developing novel protective drugs and investigating the mechanism of action for inflammatory injury in occupational populations caused by exposure to nickel and other heavy metals.

Clinicopathologic and Molecular Characterization of Xanthomatous Giant Cell Renal Cell Carcinomas: Further Support for a Close Morphologic Spectrum to Eosinophilic Solid and Cystic Renal Cell Carcinomas.

A recent study described a rare subtype of tuberous sclerosis complex ( TSC )-mutated renal cell carcinoma primarily characterized by Xanthomatous giant cell morphology. Only 2 cases in young individuals have been reported so far, making the correct diagnosis challenging from a pathological perspective. It remains unknown whether this tumor represents an independent subtype or belongs to other TSC -mutated tumors. We conducted a clinicopathologic evaluation and immunohistochemical profiling of 5 cases of Xanthomatous Giant Cell Renal Cell Carcinoma (XGC RCC) with confirmed TSC2 mutations through targeted DNA sequencing. In addition, we analyzed transcriptomic profiles using RNA-seq for the following samples: XGC RCC, Low-grade Oncocytic tumors (LOT), High-grade Oncocytic tumors/Eosinophilic Vacuolar Tumors (HOT/EVT), Eosinophilic Solid and Cystic Renal Cell Carcinomas (ESC RCC), Chromophobe cell Renal Cell Carcinomas (ChRCC), Renal Oncocytomas (RO), clear cell Renal Cell Carcinomas (ccRCC), and normal renal tissues. There were 2 female and 3 male patients, aged 22 to 58 years, who underwent radical nephrectomy for tumor removal. The tumor sizes ranged from 4.7 to 9.5 cm in diameter. These tumors exhibited ill-defined boundaries, showed an expansive growth pattern, and featured distinctive tumor giant cells with abundant eosinophilic to Xanthomatous cytoplasm and prominent nucleoli. All tumors had low Ki-67 proliferation indices (<1%) and demonstrated immune reactivity for CD10, PAX8, CK20, CathepsinK, and GPNMB. Next-generation sequencing confirmed TSC2 mutations in all cases. RNA sequencing-based clustering indicated a close similarity between the tumor and ESC RCC. One patient (1/5) died of an accident 63 months later, while the remaining patients (4/5) were alive without tumor recurrences or metastases at the time of analysis, with a mean follow-up duration of 43.4 months. Our research supports the concept that Xanthomatous giant cell renal cell carcinoma (XGC RCC) shares clinicopathological and molecular characteristics with ESC RCC and shows a relatively positive prognosis, providing further support for a close morphologic spectrum between the two. We propose considering XGC RCC as a distinct subtype of ESC RCC.

Adipocyte-targeted delivery of rosiglitazone with localized photothermal therapy for the treatment of diet-induced obesity in mice.

Obesity represents a growing public health concern and is closely associated with metabolic complications such as diabetes and fatty liver disease. Anti-obesity medications currently available have limited efficacy in weight loss and are often accompanied by adverse effects. This study proposes a localized photothermal therapy (PTT) combined with adipocyte-targeted delivery of rosiglitazone (RSG) to address obesity. Specifically, cationic albumin nanoparticles (cNPs) were synthesized to deliver RSG precisely to white adipocytes, stimulating the browning process. An IR780-loaded thermosensitive hydrogel was injected and allowed to gel in situ to afford a subcutaneous reservoir that enables localized PTT and controlled release of RSG cNPs. Notably, cNPs significantly enhanced the internalization efficiency in adipocytes in vitro and prolonged the therapeutic retention in the adipose tissue in vivo. Co-administration of RSG cNPs and PTT substantially reduced fat content, induced browning in white adipose tissue in diet-induced obese mice, and mitigated complications such as insulin resistance, fatty liver, and hyperlipidemia. The increased expression of uncoupling protein 1 contributes to enhancing energy expenditure and facilitating adipose metabolism, thereby effectively combating obesity. This therapeutic approach integrates localized PTT with adipocyte-targeted delivery to combat the global obesity epidemic thus offering a promising solution with reduced systemic toxicity and enhanced efficacy. STATEMENT OF SIGNIFICANCE: Cationic albumin nanoparticles are capable of efficient internalization in adipocytes, which may enhance drug targeting to adipose tissue. The combination of rosiglitazone-loaded cationic albumin nanoparticles and local hyperthermia effectively reduces lipid accumulation in adipocytes and induces an upregulated expression of uncoupling protein 1. The combination therapy effectively inhibits fat accumulation, induces adipocyte browning, and regulates systemic metabolism in diet-induced obese mice.

Prediction of false-positive PI-RADS 5 lesions on prostate multiparametric MRI: development and internal validation of a clinical-radiological characteristics based nomogram.

BACKGROUND: To develop a risk model including clinical and radiological characteristics to predict false-positive The Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions. METHODS: Data of 612 biopsy-naïve patients who had undergone multiparametric magnetic resonance imaging (mpMRI) before prostate biopsy were collected. Clinical variables and radiological variables on mpMRI were adopted. Lesions were divided into the training and validation cohort randomly. Stepwise multivariate logistic regression analysis with backward elimination was performed to screen out variables with significant difference. A diagnostic nomogram was developed in the training cohort and further validated in the validation cohort. Calibration curve and receiver operating characteristic (ROC) analysis were also performed. RESULTS: 296 PI-RADS 5 lesions in 294 patients were randomly divided into the training and validation cohort (208 : 88). 132 and 56 lesions were confirmed to be clinically significant prostate cancer in the training and validation cohort respectively. The diagnostic nomogram was developed based on prostate specific antigen density, the maximum diameter of lesion, zonality of lesion, apparent diffusion coefficient minimum value and apparent diffusion coefficient minimum value ratio. The C-index of the model was 0.821 in the training cohort and 0.871 in the validation cohort. The calibration curve showed good agreement between the estimation and observation in the two cohorts. When the optimal cutoff values of ROC were 0.288 in the validation cohort, the sensitivity, specificity, PPV, and NPV were 90.6%, 67.9%, 61.7%, and 92.7% in the validation cohort, potentially avoiding 9.7% unnecessary prostate biopsies. CONCLUSIONS: We developed and validated a diagnostic nomogram by including 5 factors. False positive PI-RADS 5 lesions could be distinguished from clinically significant ones, thus avoiding unnecessary prostate biopsy.

GCNGAT: Drug-disease association prediction based on graph convolution neural network and graph attention network.

Predicting drug-disease associations can contribute to discovering new therapeutic potentials of drugs, and providing important association information for new drug research and development. Many existing drug-disease association prediction methods have not distinguished relevant background information for the same drug targeted to different diseases. Therefore, this paper proposes a drug-disease association prediction model based on graph convolutional network and graph attention network (GCNGAT) to reposition marketed drugs under the distinguishment of background information. Firstly, in order to obtain initial drug-disease information, a drug-disease heterogeneous graph structure is constructed based on all known drug-disease associations. Secondly, based on the heterogeneous graph structure, the corresponding subgraphs of each group of drug-disease association pairs are extracted to distinguish different background information for the same drug from different diseases. Finally, a model combining Graph neural network with global Average pooling (GnnAp) is designed to predict potential drug-disease associations by learning drug-disease interaction feature representations. The experimental results show that adding subgraph extraction can effectively improve the prediction performance of the model, and the graph representation learning module can fully extract the deep features of drug-disease. Using the 5-fold cross-validation, the proposed model (GCNGAT) achieves AUC (Area Under the receiver operating characteristic Curve) values of 0.9182 and 0.9417 on the PREDICT dataset and CDataset dataset, respectively. Compared with other predictors on the same dataset (PREDICT dataset), GCNGAT outperforms the existing best-performing model (PSGCN), with a 1.58% increase in the AUC value. It is anticipated that this model can provide experimental reference for drug repositioning and further promote the drug research and development process.

The Value of 68Ga-PSMA PET/MRI for Classifying Patients with PI-RADS 3 Lesions on Multiparametric MRI: A Prospective Single-Center Study.

Prostate Imaging Reporting and Data System (PI-RADS) category 3 lesions remain a diagnostic challenge for detecting clinically significant prostate cancer (csPCa). This article evaluates the added value of 68Ga-labeled prostate-specific membrane antigen-11 (68Ga-PSMA) PET/MRI in classifying PI-RADS 3 lesions to avoid unnecessary biopsies. Methods: Sixty biopsy-naïve men with PI-RADS 3 lesions on multiparametric MRI were prospectively enrolled between February 2020 and October 2022. In all, 56 participants underwent 68Ga-PSMA PET/MRI and prostate systematic biopsy. 68Ga-PSMA PET/MRI was independently evaluated and reported by the 5-level PRIMARY score developed within the PRIMARY trial. Receiver-operating-characteristic curve analysis was used to estimate the diagnostic performance. Results: csPCa was detected in 8 of 56 patients (14.3%). The proportion of patients with csPCa and a PRIMARY score of 1, 2, 3, 4, and 5 was 0% (0/12), 0% (0/13), 6.3% (1/16), 38.5% (5/13), and 100% (2/2), respectively. The estimated area under the curve of the PRIMARY score was 0.91 (95% CI, 0.817-0.999). For a PRIMARY score of 4-5 versus a PRIMARY score of 1-3, the sensitivity, specificity, positive predictive value, and negative predictive value were 87.5%, 83.3%, 46.7%, and 97.5%, respectively. With a PRIMARY score of at least 4 to make a biopsy decision in men with PI-RADS 3 lesions, 40 of 48 patients (83.3%) could avoid unnecessary biopsies, at the expense of missing 1 of 8 (12.5%) csPCa cases. Conclusion: 68Ga-PSMA PET/MRI has great potential to classify patients with PI-RADS 3 lesions and help avoid unnecessary biopsies.

Varenicline solution nasal spray for dry eye disease in Chinese patients: a randomized phase 3 trial.

Background: Dry eye disease has a high prevalence and exerts a significant negative effect on quality of life. In China, there are currently no available nasal sprays to promote natural tear production in patients with dry eye disease. We therefore evaluated the efficacy and safety of OC-01 (varenicline solution) nasal spray versus vehicle in Chinese patients with dry eye disease. Methods: This was a randomized, multicenter, double-masked, vehicle-controlled, phase 3 clinical trial conducted at ophthalmology departments in 20 hospitals across China (NCT05378945). Eligible patients had a diagnosis of dry eye disease based on patient symptoms, Eye Dryness Score (EDS), Schirmer's Test (with topical anesthesia) Score (STS), and corneal fluorescein staining (CFS) score. Participants were randomly assigned 1:1 using an Interactive Web Response System (IWRS) to receive OC-01 0.6 mg/mL twice daily (BID) or vehicle nasal spray. Participants, investigators, and sponsor were all masked to treatment assignment. The primary endpoint was the percentage of subjects in the intention-to-treat population achieving ≥10 mm improvement in STS from baseline at week 4. Findings: In total, 340 patients were randomized from 21 July 2022 to 04 April 2023, 78.8% were female. Patients in the OC-01 group (n = 176) had significantly higher achievement of ≥10 mm improvement in STS (35.8% [n = 63] versus 17.7% [n = 29], stratified odds ratio: 2.67, 95% CI: 1.570-4.533, p = 0.0002) and a significantly greater increase from baseline STS (least-squares mean difference [SE]: 3.87 [0.794], p < 0.0001) at week 4 versus the vehicle group (n = 164). In addition, OC-01 led to a numerically greater reduction in mean EDS from baseline at week 4 compared to the vehicle group (LS mean [SE] difference: -1.3 [2.20]; 95% CI: -5.64 to 2.99, p = 0.5467). The most common adverse event was mild, transient sneezing (78% of OC-01 administrations). No serious adverse events related to nasal administration occurred. Interpretation: OC-01 (varenicline solution) nasal spray BID has clinically meaningful efficacy for reducing the signs (as measured by STS) and may improve the symptoms (as measured by EDS) of dry eye disease, with an excellent safety and tolerability profile, in the Chinese population. Funding: Jixing Pharmaceutical Co. Ltd.

Modified Retzius-sparing robot-assisted radical prostatectomy for cases with anterior tumor: a propensity score-matched analysis.

OBJECTIVE: To compare the outcomes between a modified Retzius-sparing robot-assisted radical prostatectomy (mRS-RARP) technique and conventional robot-assisted radical prostatectomy (Con-RARP) technique for cases with anterior prostate cancer (PCa), especially positive surgical margin (PSM) rates and urinary continence (UC). PATIENTS AND METHODS: We retrospectively included 193 mRS-RARP and 473 Con-RARP consecutively performed by a single surgeon for anterior PCa. Perioperative complications, pathology, and continence were compared after propensity score matching using 9 variables. RESULTS: After matching (n = 193 per group), PSM were not significantly different in the two groups (16.1% in mRS-RARP group vs. 15.0% in Con-RARP group, p = 0.779). The UC at catheter removal and at 1-month was significantly higher in the mRS-RARP (24.9% vs. 9.8%, p < 0.001; 29.0% vs. 13.5%, p < 0.001, respectively), but not at 3-, 6-, and 12-month follow-ups (p = 0.261, 0.832, and 0.683, respectively). CONCLUSION: mRS-RARP seems to be an oncologically safe approach for patients with anterior PCa. Compared with the conventional approach, mRS-RARP approach shows benefits in the short-term postoperative UC recovery.

Zein-Based Triple-Drug Nanoparticles to Promote Anti-Inflammatory Responses for Nerve Regeneration after Spinal Cord Injury.

Defects in autophagy contribute to neurological deficits and motor dysfunction after spinal cord injury. Here a nanosystem is developed to deliver autophagy-promoting, anti-inflammatory drugs to nerve cells in the injured spinal cord. Celastrol, metformin, and everolimus as the mTOR inhibitor are combined into the zein-based nanoparticles, aiming to solubilize the drugs and prolong their circulation. The nanoparticles are internalized by BV2 microglia and SH-SY5Y neuron-like cells in culture; they inhibit the secretion of inflammatory factors by BV2 cells after insult with lipopolysaccharide, and they protect SH-SY5Y cells from the toxicity of H2O2. In a rat model of spinal cord injury, the nanoparticles mitigate inflammation and promote spinal cord repair. In the in vitro and in vivo experiments, the complete nanoparticles function better than the free drugs or nanoparticles containing only one or two drugs. These results suggest that the triple-drug nanoparticles show promise for treating spinal cord injury.

Massively parallel reporter assay confirms regulatory potential of hQTLs and reveals important variants in lupus and other autoimmune diseases.

We designed a massively parallel reporter assay (MPRA) in an Epstein-Barr virus transformed B cell line to directly characterize the potential for histone post-translational modifications, i.e., histone quantitative trait loci (hQTLs), expression QTLs (eQTLs), and variants on systemic lupus erythematosus (SLE) and autoimmune (AI) disease risk haplotypes to modulate regulatory activity in an allele-dependent manner. Our study demonstrates that hQTLs, as a group, are more likely to modulate regulatory activity in an MPRA compared with other variant classes tested, including a set of eQTLs previously shown to interact with hQTLs and tested AI risk variants. In addition, we nominate 17 variants (including 11 previously unreported) as putative causal variants for SLE and another 14 for various other AI diseases, prioritizing these variants for future functional studies in primary and immortalized B cells. Thus, we uncover important insights into the mechanistic relationships among genotype, epigenetics, and gene expression in SLE and AI disease phenotypes.

PbS/CsPbBr3 Heterojunction for Broadband Neuromorphic Vision Sensing.

Neuromorphic light sensors with analogue-domain image processing capability hold promise for overcoming the energy efficiency limitations and latency of von Neumann architecture-based vision chips. Recently, metal halide perovskites, with strong light-matter interaction, long carrier diffusion length, and exceptional photoelectric conversion efficiencies, exhibit reconfigurable photoresponsivity due to their intrinsic ion migration effect, which is expected to advance the development of visual sensors. However, suffering from a large bandgap, it is challenging to achieve highly tunable responsivity simultaneously with a wide-spectrum response in perovskites, which will significantly enhance the image recognition accuracy through the machine learning algorithm. Herein, we demonstrate a broadband neuromorphic visual sensor from visible (Vis) to near-infrared (NIR) by coupling all-inorganic metal halide perovskites (CsPbBr3) with narrow-bandgap lead sulfide (PbS). The PbS/CsPbBr3 heterostructure is composed of high-quality single crystals of PbS and CsPbBr3. Interestingly, the ion migration of CsPbBr3 with the implementation of an electric field induces the energy band dynamic bending at the interface of the PbS/CsPbBr3 heterojunction, leading to reversible, multilevel, and linearly tunable photoresponsivity. Furthermore, the reconfigurable and broadband photoresponse in the PbS/CsPbBr3 heterojunction allows convolutional neuronal network processing for pattern recognition and edge enhancements from the Vis to the NIR waveband, suggesting the great potential of the PbS/CsPbBr3 heterostructure in artificial intelligent vision sensing.

Si/CuO Heterojunction-Based Photomemristor for Reconfigurable, Non-Volatile, and Self-Powered In-Sensor Computing.

In-sensor computing has attracted considerable interest as a solution for overcoming the energy efficiency and response time limitations of the traditional von Neumann architecture. Recently, emerging memristors based on transition-metal oxides (TMOs) have attracted attention as promising candidates for in-memory computing owing to their tunable conductance, high speed, and low operational energy. However, the poor photoresponse of TMOs presents challenges for integrating sensing and processing units into a single device. This integration is crucial for eliminating the need for a sensor/processor interface and achieving energy-efficient in-sensor computing systems. In this study, a Si/CuO heterojunction-based photomemristor is proposed that combines the reversible resistive switching behavior of CuO with the appropriate optical absorption bandgap of the Si substrate. The proposed photomemristor demonstrates a simultaneous reconfigurable, non-volatile, and self-powered photoresponse, producing a microampere-level photocurrent at zero bias. The controlled migration of oxygen vacancies in CuO result in distinct energy-band bending at the interface, enabling multiple levels of photoresponsivity. Additionally, the device exhibits high stability and ultrafast response speed to the built-in electric field. Furthermore, the prototype photomemristor can be trained to emulate the attention-driven nature of the human visual system, indicating the tremendous potential of TMO-based photomemristors as hardware foundations for in-sensor computing.

Chondroitin Sulfate-Derived Micelles for Adipose Tissue-Targeted Delivery of Celastrol and Phenformin to Enhance Obesity Treatment.

Adipose tissue macrophages (ATMs) are crucial in maintaining a low-grade inflammatory microenvironment in adipose tissues (ATs). Modulating ATM polarization to attenuate inflammation represents a potential strategy for treating obesity with insulin resistance. This study develops a combination therapy of celastrol (CLT) and phenformin (PHE) using chondroitin sulfate-derived micelles. Specifically, CLT-loaded 4-aminophenylboronic acid pinacol ester-modified chondroitin sulfate micelle (CS-PBE/CLT) and chondroitin sulfate-phenformin conjugate micelles (CS-PHE) were synthesized, which were shown to actively target ATs through CD44-mediated pathways. Furthermore, the dual micellar systems significantly reduced inflammation and lipid accumulation via protein quantification and Oil Red O staining. In preliminary in vivo studies, we performed H&E staining, immunohistochemical staining, insulin tolerance test, and glucose tolerance test, and the results showed that the combination therapy using CS-PBE/CLT and CS-PHE micelles significantly reduced the average body weight, white adipose tissue mass, and liver mass of high-fat diet-fed mice while improving their systemic glucose homeostasis. Overall, this combination therapy presents a promising alternative to current treatment options for diet-induced obesity.