All-trans retinoic acid-mediated ADAR1 degradation synergizes with PD-1 blockade to suppress pancreatic cancer.

As a double-stranded RNA-editing enzyme and an interferon-stimulated gene, double-stranded RNA-specific adenosine deaminase (ADAR1) suppresses interferon signaling and contributes to immunotherapy resistance. Suppression of ADAR1 overcomes immunotherapy resistance in preclinical models, but has not yet been translated to clinical settings. By conducting a screening of a subset of the FDA-approved drugs, we found that all-trans retinoic acid (ATRA, also known as tretinoin) caused ADAR1 protein degradation through ubiquitin-proteasome pathways and concomitantly increased PD-L1 expression in pancreatic and breast cancers. In addition, the combination of ATRA and PD-1 blockade reprogrammed the tumor microenvironment and unleashed antitumor immunity and thereby impeded tumor growth in pancreatic cancer mouse models. In a pilot clinical trial, a higher dose of ATRA plus the anti-PD-1 antibody nivolumab prolonged median overall survival in patients with chemotherapy-resistant pancreatic cancer compared to a lower dose of the same regimen. In this study, ATRA was the first drug to be found to cause ADAR1 degradation. We propose translation of a promising 2-pronged antitumor strategy using ATRA and nivolumab to convert immunologically "cold" into "hot" tumors susceptible to immune checkpoint blockade.

Highly Tunable 2D Silicon Quantum Dot Array with Coupling beyond Nearest Neighbors.

Scaling up quantum dots to two-dimensional (2D) arrays is a crucial step for advancing semiconductor quantum computation. However, maintaining excellent tunability of quantum dot parameters, including both nearest-neighbor and next-nearest-neighbor couplings, during 2D scaling is challenging, particularly for silicon quantum dots due to their relatively small size. Here, we present a highly controllable and interconnected 2D quantum dot array in planar silicon, demonstrating independent control over electron fillings and the tunnel couplings of nearest-neighbor dots. More importantly, we also demonstrate the wide tuning of tunnel couplings between next-nearest-neighbor dots, which play a crucial role in 2D quantum dot arrays. This excellent tunability enables us to alter the coupling configuration of the array as needed. These results open up the possibility of utilizing silicon quantum dot arrays as versatile platforms for quantum computing and quantum simulation.

Expression profiles of urine exosomal tRNA-derived small RNAs and their potential roles in calcium oxalate stone disease.

Background and objective: Exosomes have been confirmed to be implicated in the pathogenesis of calcium oxalate (CaOx) stones. tRNA-derived small RNAs (tsRNAs) are among the oldest small RNAs involved in exosome-mediated intercellular communication, yet their role in kidney stones remains unexplored. This pilot study aimed to identify differentially expressed tsRNAs (DEtsRNAs) in urine exosomes between CaOx stone patients and healthy controls and explore their potential roles in nephrolithiasis. Method: First-morning urine samples were collected from three CaOx stone patients and three healthy controls. Urinary exosomes were isolated and analyzed by high-throughput sequencing to generate the expression profiles of tsRNAs and detect DEtsRNAs. Predicted target genes of DEtsRNAs were subjected to functional enrichment analysis. The authors also combined the public dataset GSE73680 to investigate how DEtsRNAs were related to stone formation. Results: Four DEtsRNAs were significantly upregulated in CaOx stone patients compared to healthy controls. tRF-Lys-TTT-5005c was the most elevated, followed by tRF-Lys-CTT-5006c, tRF-Ala-AGC-5017b, and tRF-Gly-CCC-5004b. Bioinformatics analysis indicated that these four types of DEtsRNAs might serve distinct biological functions. Combined with data mining from the public dataset GSE73680, the authors assumed that exosomes carrying tRF-Lys-TTT-5005c and tRF-Lys-CTT-5006c could inhibit the expression of SMAD6, FBN1, and FZD1, thereby activating the BMP signaling pathway, which might induce an osteogenic-like transformation in target cells, resulting in the formation of Randall's plaques and CaOx stones. Conclusion: The authors' findings shed light on the potential roles of tsRNAs in the pathogenesis of CaOx stone disease, highlighting exosomal DEtsRNAs as promising diagnostic biomarkers and therapeutic targets in nephrolithiasis.

Excessive or sustained endoplasmic reticulum stress: one of the culprits of adipocyte dysfunction in obesity.

As the prevalence of obesity continues to rise globally, the research on adipocytes has attracted more and more attention. In the presence of nutrient overload, adipocytes are exposed to pressures such as hypoxia, inflammation, mechanical stress, metabolite, and oxidative stress that can lead to organelle dysfunction. Endoplasmic reticulum (ER) is a vital organelle for sensing cellular pressure, and its homeostasis is essential for maintaining adipocyte function. Under conditions of excess nutrition, ER stress (ERS) will be triggered by the gathering of abnormally folded proteins in the ER lumen, resulting in the activation of a signaling response known as the unfolded protein responses (UPRs), which is a response system to relieve ERS and restore ER homeostasis. However, if the UPRs fail to rescue ER homeostasis, ERS will activate pathways to damage cells. Studies have shown a role for disturbed activation of adipocyte ERS in the pathophysiology of obesity and its complications. Prolonged or excessive ERS in adipocytes can aggravate lipolysis, insulin resistance, and apoptosis and affect the bioactive molecule production. In addition, ERS also impacts the expression of some important genes. In view of the fact that ERS influences adipocyte function through various mechanisms, targeting ERS may be a viable strategy to treat obesity. This article summarizes the effects of ERS on adipocytes during obesity.

Loss of tyrosine 211 phosphorylation of proliferating cell nuclear antigen (PCNA) enhances postnatal mammary gland development.

The intricately orchestrated progression of mammary tissue development involves the precise coordination of gland differentiation and cellular proliferation. Nevertheless, the understanding of the role and regulatory mechanisms governing the DNA replication machinery in mammary gland development remains limited. Given the essential role of DNA replication in the viability of living cells, any genetic disturbance to its replicative function, in any form, will impede organ development. This circumstance poses a technical challenge in elucidating the potential function of cell proliferation in mammary morphogenesis. PCNA is crucial in DNA replication, playing a pivotal role in the development of complete eukaryotic organisms. The phosphorylation of PCNA at tyrosine 211 (Y211) has been demonstrated to play a significant role in supporting replication forks and, consequently, cell proliferation. Therefore, the utilization of a knock-in mouse model, wherein the Y211 residue of PCNA is replaced with phenylalanine (211F), presents an opportunity to evaluate the impact of reduced cell proliferation potential on mammary gland development. Interestingly, the lack of Y211 phosphorylation did not significantly impact the rates of proliferation or cell death in the mammary gland. In contrast, the absence of Y211PCNA led to an increased, rather than reduced, growth of the mammary gland. This was evident in assessments of gland length and the number of terminal end buds (TEBs) in both postnatal and virgin mammary glands. Notably, this observation correlated with an elevation in tissue stemness within the 211F glands compared to the WT glands. Additionally, it was consistent with the greater body weight gains observed in 211F pups compared to WT pups during the weaning period. Our findings unveil an unexpected aspect that may carry significance for mammary development. This newfound is associated with the regulation of a central component within the DNA replication machinery, providing insights into the intricate interplay governing mammary tissue expansion.

Knowledge mapping of telemedicine in urology in the past 20 years: A bibliometric analysis (2004-2024).

Telemedicine refers to the process of utilizing communication technologies to exchange disease information, perform surgery and educate care providers remotely, breaking through the distance limit and promoting the health of individuals and communities. The fifth-generation (5G) technology and the COVID-19 pandemic have greatly boosted studies on the application of telemedicine in urology. In this study, we conduct a comprehensive overview of the knowledge structure and research hotspots of telemedicine in urology through bibliometrics. We searched publications related to telemedicine in urology from 2004 to 2024 on the Web of Science Core Collection (WoSCC) database. VOSviewer, CiteSpace and R package "bibliometrix" were employed in this bibliometric analysis. A total of 1,357 articles from 97 countries and 2,628 institutions were included. The number of annual publications on telemedicine in urology witnessed a steady increase in the last two decades. Duke University was the top research institution. Urology was the most popular journal, and Journal of Medical Internet Research was the most co-cited journal. Clarissa Diamantidis and Chad Ellimoottil published the most papers, and Boyd Viers was co-cited most frequently. Effectiveness evaluation of telemonitoring, cost-benefit analysis of teleconsultation and exploration of telesurgery are three main research hotspots. As the first bibliometric analysis of research on telemedicine in urology, this study reviews research progress and highlights frontiers and trending topics, offering valuable insights for future studies.

Clinical characteristics of lean metabolic-associated fatty liver disease and the impact of concurrent diabetes mellitus.

Objectives: Metabolic-associated fatty liver disease (MAFLD) was proposed in 2020 to replace the original term nonalcoholic fatty liver disease (NAFLD) with new diagnostic criteria. The disease risks of lean and overweight/obese MAFLD patients remain controversial. Materials and Methods: The participants from the Taiwan biobank cohort were included. Advanced liver fibrosis is defined as NAFLD fibrosis score (NFS) >0.675. We use carotid plaques of duplex ultrasounds to diagnose atherosclerosis. Results: A total of 20,058 participants (age 55.67 ± 10.32; males 37.6%) were included in the final analysis. Seven thousand eight hundred and forty-three (39.1%) participants were diagnosed with MAFLD. Of them, 965 (12.3%) were lean MAFLD patients. Among lean MAFLD patients, 25.6% were comorbid with diabetes mellitus (DM). Lean MAFLD patients were older and had higher percentages of females and DM than overweight/obese MAFLD patients. After propensity score matching for age and sex, they had lower levels of NFS but a higher percentage of carotid plaques. Among four subtypes of MAFLD including "lean with DM," "lean without DM," "overweight/obese with DM," and "overweight/obese without DM," logistic regression showed that "lean with DM" subjects had the highest risk of atherosclerosis and "overweight/obese with DM" subjects had the highest risk of advanced liver fibrosis in MAFLD patients. Conclusion: The population-based study revealed that lean MAFLD patients make up 12.3% of all MAFLD patients, and they have a higher proportion of coexisting diabetes. Among lean MAFLD patients concurrent with diabetes, they have the highest risk of atherosclerosis and should receive special attention clinically.

Lenvatinib Plus Pembrolizumab versus Doxorubicin for Advanced or Recurrent Endometrial Cancer with Short Treatment-Free Intervals Following First-Line Carboplatin Plus Paclitaxel.

Background: The treatment-free interval is a significant predictor of worse prognosis and poor response rates of the second-line treatment in patients with carboplatin and paclitaxel (PT)-pretreated, advanced, or recurrent endometrial cancer (EC). Whether lenvatinib plus pembrolizumab still confers a survival benefit compared with doxorubicin in patients with platinum-free intervals of <6 months remains unclear. Methods: This multi-institutional retrospective analysis was performed using de-identified electronic health records from the TriNetX Research Network. Patients with advanced or recurrent ECs who received lenvatinib plus pembrolizumab or doxorubicin within six months of first-line PT were identified. A 1:1 propensity score matching (PSM) was conducted to control for potential confounding variables. Overall survival (OS) and adverse event profile were the primary and secondary outcomes. Results: Between January 2018 and February 2024, 130 patients with PT-treated, advanced, or recurrent ECs who received lenvatinib plus pembrolizumab and 122 patients who received doxorubicin at a platinum-free interval of <6 months were identified across 31 healthcare organizations. In the balanced cohort following PSM with 117 patients in each group, treatment with lenvatinib plus pembrolizumab was associated with improved OS compared with treatment with doxorubicin (12.8 vs. 8.2 months, p = 0.012, hazard ratio: 0.65, 95% confidence interval: 0.46-0.91). Regarding adverse event analysis, a higher incidence of hypothyroidism and proteinuria was observed with lenvatinib plus pembrolizumab, and more hematological toxicities were observed with doxorubicin. Conclusions: in patients with treatment-free intervals of <6 months, lenvatinib plus pembrolizumab still confers improved survival compared with doxorubicin in PT-treated, advanced, or recurrent ECs.

Effects of earthworm and arbuscular mycorrhizal fungal inoculation on carbon component accumulation and allocation in rocky desertification soils.

Exploring the responses of carbon component accumulation and allocation to arbuscular mycocorrhizal fungi (AM) and earthworm inoculation can provide reference for improving carbon sequestration potential and bioremediation efficiency in rocky desertification soils. In this study, we chose Fraxinus malacophylla as the host plant to inoculate with Funneliformis mosseae (FM), earthworm (E), and E+FM, using no earthworm and mycorrhizae addition as CK to examine the spatiotemporal variations in soil carbon components (i.e., total organic carbon, microbial biomass carbon, easily oxidized organic carbon, and recalcitrant organic carbon) and their allocation (i.e., microbial biomass carbon/total organic carbon, easily oxidized organic carbon/total organic carbon, and recalcitrant organic carbon/total organic carbon). The results showed that 1) The respective and interactive inoculation of E and AM significantly promoted the accumulation of each carbon component. In contrast with the control, the average carbon component levels under three inoculation treatments were ranked as E+FM>E>FM. The three inoculation treatments significantly promoted soil microbial carbon/total organic carbon (30.5%-68.5%) and easily oxidized carbon/total organic carbon (31.2%-39.2%), but decreased recalcitrant organic carbon/total organic carbon (2.9%-16.2%). 2) The spatiotemporal variation in accumulation and allocation of soil carbon components varied between the inoculation treatments. The maximum value of each carbon component occurred in June. The increase in each carbon component was significantly higher in E+FM (33.0%-122.1%) than that in E (31.2%-95.4%) and FM (9.2%-41.3%). The maximum value of microbial biomass carbon/total organic carbon and easily oxidized organic carbon/total organic carbon was observed in June, while that of recalcitrant organic carbon/total organic carbon was recorded in December. In contrast with CK, the amplitude of variation in the proportion of carbon components in total organic carbon under the three inoculation treatments was ranked as E+FM>E>FM. The accumulation and allocation of all carbon components decreased (9.7%-146.2%) along the soil profile. The level of carbon components in the E treatment decreased the smallest. The microbial biomass carbon/total organic carbon and easily oxidized carbon/total organic carbon decreased the least and the recalcitrant organic carbon/total organic carbon decreased the greatest under the E+FM treatment. 3) Changes in soil physicochemical properties under the three inoculation treatments significantly affected the accumulation and allocation of organic carbon components. Soil pH was negatively correlated with carbon component accumulation and allocation, whereas other soil variables were positively correlated with them. 4) The results of principal component analysis showed that soil water content, total nitrogen, and total phosphorus were the main factors driving carbon component accumulation, while soil water content, total phosphorus, and pH were the main factors controlling carbon component allocation. Therefore, we concluded that the earthworms, AM fungi and their interaction affected the accumulation and allocation of carbon components in Yunnan rocky desertification soils, which would primarily depend on the changes of soil water content, acid-base property, as well as nitrogen and phosphorus conditions.

Halogen-Bond-Assisted NHC-Catalyzed (Dynamic) Kinetic Resolution for the Atroposelective Synthesis of Heterobiaryls.

We report a novel halogen-bond-assisted NHC-catalyzed (dynamic) kinetic resolution strategy for the synthesis of axially chiral heterobiaryls. A class of axially chiral quinolines are prepared efficiently in excellent enantioselectivities (≤98% ee) employing 3-5 mol % NHC catalyst. Mechanistic studies reveal the indispensability of 5-bromo-2-iodobenzaldehyde in this reaction, in which a pivotal halogen bonding interaction plays a crucial role in the process.

The role of TERT C228T and KDM6A alterations and TME in NMIBC treated with BCG.

We aimed to investigate the genomic and tumor microenvironmental (TME) profiles in non-muscle invasive bladder cancer (NMIBC) and explore potential predictive markers for Bacillus Calmette-Guérin (BCG) treatment response in high-risk NMIBC patients (according to European Association of Urology (EAU) risk stratification). 40 patients with high-risk NMIBC (cTis-T1N0M0) who underwent en bloc resection followed by BCG instillation were retrospectively enrolled. Surgical samples were subjected to Next Generation Sequencing (NGS) and multiplex immunofluorescence (mIF) assay. Genomic profiling revealed high prevalences of alterations in TERT (55%), KDM6A (32.5%), FGFR3(30%), PIK3CA (30%), TP53(27.5%) and ARID1A (20%). TME analysis showed different proportions of macrophages, NK cells, T cells subsets in tumoral and stromal compartment. Multivariate analysis identified TERT C228T and alteration in KDM6A as two independent factors associated with inferior RFS. The study comprehensively depicted the genomic and TME profiles in NMIBC and identified potential predictive biomarkers for BCG treatment.

Ultra-high PDCR(>109) of vacuum-UV photodetector based on Al-doped Ga2O3microbelts.

Al-doped Ga2O3microbelts with widths ranging from 20 to 154µm and lengths up to 2 mm were grown using carbothermal reduction. Based on these ultra-wide microbelts, single-microbelt (37µm wide) and double-microbelts(38µm/42µm wide) metal-semiconductor-metal photoconductive ultraviolet (UV) detectors PDs were fabricated and their optoelectronic performances were investigated at Vacuum-UV (VUV) wavelengths of 185 nm. Under irradiation of 185 nm, the Al-doped Ga2O3PD has a very-high photocurrent (Iph) of 192.07µA and extremely low dark current (Id) of 156 fA at 10 V, and presents a ultra-high light-to-dark current ratio of 1.23 × 109. The responsivity (R), external quantum efficiency (EQE), and detectivity (D*) of the double-microbelts detector device were 1920 A W-1, 9.36 × 105%, and 8.6 × 1016Jones, respectively. Since the bandgap of the Al-doped microbelts becomes wider, and the fabricated detector has weaker sensitivity to radiation in the 254/365 nm wavelengths. Compared with the 254 nm and 365 nm UV cases, the devices under 185 nm VUV show the excellent high selectivity ratios of 1.47 × 106and 1.7× 107, respectively. This paper should provide a new insight on the VUV photodetectors utilizing Ga2O3microbelts.

Recent breakthroughs in innovative elements, multidimensional enhancements, derived technologies, and novel applications of PROTACs.

Proteolysis Targeting Chimera (PROTAC) is an emerging and evolving technology based on targeted protein degradation (TPD). Small molecule PROTACs have shown great efficacy in degrading disease-specific proteins in preclinical and clinical studies, but also showed various limitations. In recent years, new technologies and advances in TPD have provided additional optimized strategies based on conventional PROTACs that can overcome the shortcomings of conventional PROTACs in terms of undruggable targets, bioavailability, tissue-specificity, spatiotemporal control, and degradation scope. In addition, some designs of special targeting chimeras and applications based on multidisciplinary science have shed light on novel therapeutic modalities and drug design. However, each improvement has its own advantages, disadvantages and application conditions. In this review, we summarize the exploration of PROTAC elements, depict a landscape of improvements and derived concepts of PROTACs, and expect to provide perspectives for technological innovations, combinations and applications in future targeting chimera design.

Dietary Clostridium butyricum metabolites mitigated the disturbances in growth, immune response and gut health status of Ctenopharyngodon idella subjected to high cottonseed and rapeseed meal diet.

Cottonseed meal and rapeseed meal exhibit a potential for fishmeal substitute in grass carp feed, while their excessive use contribute to growth decline and weakening immunity of aquatic animals. Clostridium butyricum metabolites (CBM) was recognized as a functional additive due to its antioxidant properties and maintenance of intestinal microbiota balance. CBM was added to a high of cottonseed and rapeseed meal diet to determine its effects on growth, immunity, and intestinal microbiota alterations of grass carp (Ctenopharyngodon idella) over 56 days. Eight hundred grass carp (mean weight, around 50 g) were randomized to five treatments and fed with the basic diet (CON), CBM0 diet (28 % cottonseed and 27 % rapeseed meal), and CBM diets (CBM0.5, CBM1, and CBM2, namely CBM0 diet supplemented with 500, 1000, and 2000 mg kg-1 CBM). The results indicated that compared to CBM0, The ingestion of 1000 mg kg-1 CBM diet by grass carp significantly promoted growth as measured by intestinal lipase activity, villus height, and muscle thickness. Moreover, accompanied by a decrease in intestine MDA content, and enhance antioxidant capacity by activating Keap1/Nrf2 signaling pathway to increase enzyme activities (SOD, CAT and T-AOC) and corresponding gene expression (mnsod, cat, gsto and gpx1) in the intestine of grass crap fed CBM1 diet. The dietary CBM1 diet increased serum levels of C3 and IgM, increased ACP activity and expression of the corresponding anti-inflammatory factors (tgf-ß1 and il-15), and suppressed the expression of pro-inflammatory factors (tnf-α and il-12ß), resulting in enhanced immunity. The dietary CBM1 diet up-regulates gene expression of tight junction proteins (zo-1, occludin, occludin7a and occludin-c), coupled with the decreases in DAO and D-lactate contents, implying that the decreased mucosal permeability could be observed in the gut. The dietary CBM1 diet largely altered the intestinal microbial community, especially reducing the relative abundance of intestinal pathogenic bacteria (Streptococcus and Actinomyces). And it significantly increased the content of short-chain fatty acids (acetic acid, butyric acid, isobutyric acid, propionic acid and isovaleric acid). Taken above, dietary CBM supplementation improved growth in grass carp and attenuated the intestinal oxidative stress, inflammation and microflora dysbacteriosis caused by high proportions of cottonseed and rapeseed meal diets.

CD74 is a potential biomarker predicting the response to immune checkpoint blockade.

BACKGROUND: Immune checkpoint blockade (ICB) has been improving the patient outcome in multiple cancer types. However, not all patients respond to ICB. Biomarkers are needed for selecting appropriate patients to receive ICB. CD74 is an important chaperone that regulates antigen presentation for immune response. However, the relationship between CD74 expression and ICB response remains elusive. METHODS: The unified normalized pan-cancer dataset was downloaded from the UCSC database. Wilcoxon Rank Sum Rank Tests were used to analyze the expression differences between normal and tumor samples in each tumor type. Then, the prognostic value of CD74 was determined using univariable Cox proportional hazards regression analysis. The STRING database was utilized to construct the protein-protein interaction (PPI) network of CD74 and the signal pathways were analyzed as well. The correlation of CD74 expression with immune cells and immune regulating genes was investigated in the TIMER database. The TIDE framework was utilized to evaluate the relationship between CD74 expression and the response to immunotherapy. Moreover, the localization of CD74 in the tumor immune microenvironment was verified using multiplex immunohistochemistry. Clinically annotated samples from 38 patients with esophageal cancer treated with neoadjuvant chemotherapy combined with ICB were analyzed for CD74 expression using immunohistochemistry. RESULTS: In this study, we investigated the prognostic and predictive value of CD74 in different types of cancer. Compared with normal tissue, the expression of CD74 was higher in tumor tissue in various cancers. High expression of CD74 was associated with improved patient prognosis in the majority of cancers. CD74 and its interacting proteins were mainly enriched in the immune-related pathways. The expression of CD74 was significantly positively correlated with B cells, CD4 T-cells, CD8 T-cells, neutrophils, macrophages and dendritic cells. TIDE analysis showed that tumors with high CD74 expression may have better responses to immunotherapy and improved patient survival. In patients with esophageal cancer who had received ICB, higher intratumoral CD74 expression was associated with improved response to ICB. CONCLUSIONS: The findings of this study suggest that the high expression of CD74 may be a potential predictive biomarker of response to ICB.

Designing High-Performance Nanoscale Spin-MOSFET Devices by Using Two-Dimensional Half-Metallic Cr2Se3.

Constructing nanoscale spin devices has been a crucial pursuit in the field of nano spintronics. Here, by using the density functional theory (DFT) and nonequilibrium Green's function (NEGF) method, high-performance nanoscale spin-MOSFET devices using half-metallic 2D Cr2Se3 as electrodes are theoretically designed. Specifically, seven typical two-dimensional (2D) semiconductors, Sb, Bi, BP, BAs, MoTe2, WTe2, and WSeTe (with two different contacting surfaces), are considered here as the channel materials. The properties of contact interfaces between these 2D semiconductors and half-metallic 2D Cr2Se3 are first investigated. It is found that except BP and BAs (having Schottky contacts with Cr2Se3), the other 2D semiconductors have vertical Ohmic contacts with Cr2Se3 among which Cr2Se3/Sb, Cr2Se3/MoTe2, Cr2Se3/WTe2, Cr2Se3/WSeTe-Se, and Cr2Se3/WSeTe-Te retain the half-metallic characteristic. Then, these 2D semiconductors with Ohmic vertical contacts are further used to construct spin-MOSFET devices. The results show that devices constructed by half-metallic vertical contacting systems have nearly 100% SIE and therefore giant MR (>107%) when the gate voltage varies. Furthermore, four designed spin-MOSFET devices, namely, Cr2Se3/MoTe2, Cr2Se3/WTe2, Cr2Se3/WSeTe-Se, and Cr2Se3/WSeTe-Te spin-MOSFET have high efficient gate modulations on the magnitude of completely spin-polarized source-drain current with Cr2Se3/WTe2 having the smallest SS value of 134.1 mV/dec. The calculations suggest that Cr2Se3 is a good candidate for constructing spin-MOSFET devices. Our study sheds light on the design of high-performance nanoscale spin-MOSFET devices by using two-dimensional half-metallic electrodes.

[Comparative study of total hip arthroplasty with and without femoral osteotomy in Crowe â £ developmental dysplasia of the hip].

OBJECTIVE: To compare the clinical effects of total hip arthroplasty(THA) with and without femoral osteotomy in Crowe Ⅳ developmental hip dislocation(DDH). METHODS: The data on 46 patients who underwent THA for unilateral Crowe Ⅳ DDH between 2012 and 2017 were analyzed retrospectively. They were divided into two groups according to the different surgical methods. There were 24 patients in the osteotomy group, 3 males and 21 females, with an average age of (47.3±9.0) years old ranged from 34 to 57 years old;and 22 patients in the non-osteotomy group, 2 males and 20 females, with an average age of (51.6±8.3) years old ranged from 40 to 61 years old. The operative time, bleed loss, postoperative drainage volume, postoperative complications, ROM of hip, Harris hip score, limb length discrepancy(LLD), and radiological data were recorded. The femoral dislocation height and the implantation depth of sleeve were measured. RESULTS: All patients were followed up. The mean follow-up time was (3.8±1.2) years ranged from 2 to 6 years in the osteotomy group and (3.2±0.9) years ranged from 1 to 5 years in the non-osteotomy group. The operative time(136.8±18.9) min, bleed loss (709.8±89.4) ml, postoperative drainage volume(308.8±98.2) ml of osteotomy group were all significantly greater than those of non-osteotomy group(100.7±15.8)min, (516.5±103.3) ml, (245.3±79.3) ml (P<0.05). The Harris score at the latest follow up was significantly increased compared with preoperative score in two groups (P<0.05), but there was no significant difference between two groups (P>0.05). The LLD at last follow up was significantly increased compared with preoperative LLD in two groups, the LLD in non-osteotomy group(0.7±0.2) cm showed signifcant smaller than the two osteotomy group(1.2±0.4) cm. Between osteotomy and non-osteotomy groups, the preoperative range of motion of hip joint [(89.5±19.7) °vs (102.5±16.8) °], the preoperative height of dislocation of femoral head [(4.56±0.61) cm vs (3.10±0.73) cm], the proximal implant depth of S-ROM [(0.93±0.36) cm vs (1.67±0.28) cm] was significantly different (P<0.05). Eleven patients in the osteotomy group still had claudication, and 4 patients in the non-osteotomy group had mild claudication (P<0.05). In non-osteotomy group, 3 patients developed nerve injury (1 patient of sciatic nerve, 2 patients of femoral nerve) and 1 case developed periprosthetic fracture. In osteotomy group, 2 case of dislocation and 2 cases of periprosthetic fractures. CONCLUSION: Whether osteotomy or not can achieve satisfactory results for treating Crowe type Ⅳ DDH and significantly improve LLD. However, osteotomy is more complex and time-consuming, limb length difference is greater, and the incidence of claudication is higher. Furthermore, patients with smaller preoperative hip mobility, higher femoral dislocation, limb lengthening≥4 cm and severely narrow femoral proximal canals are prone to be peformed with subtrochanteric osteotomy.

Drug-associated glaucoma: A real-world study based on the Food and Drug Administration adverse event reporting system database.

BACKGROUND: This study aims to assess the risk of drug-associated glaucoma and track its epidemiological characteristics using real-world data. METHODS: Adverse event reports from the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to December 2023 were analysed. Disproportionality analysis and the Bayesian Confidence Propagation Neural Network algorithm were used. The study classified drugs associated with glaucoma, assessed risk levels, and compared drug-induced times across different categories. RESULTS: Eight hundred and five drugs were linked to glaucoma in the FAERS database. Disproportionality analysis identified 46 drugs with significant risk, mainly adrenergic medications (clobetasol propionate, fluocinolone acetonide), antihypertensives (hydrochlorothiazide), insulin (insulin human), anticholinergics (umeclidinium, darifenacin), VEGF inhibitors (brolucizumab, faricimab), and psychotropics (topiramate, ziprasidone). The top three high-risk drugs were clobetasol propionate, umeclidinium, and fluocinolone acetonide. The shortest drug-induced times were observed with indacaterol, salmeterol, and umeclidinium. Anticholinergic medications had the shortest drug-induced time among all categories. Females (62.5%) and the elderly (average age 63.5 ± 16.8 years) were predominantly affected. Reports of drug-associated glaucoma increased over the years. CONCLUSION: Preventing drug-associated glaucoma is more effective than treatment. Identifying the risk and drug-induced times of systemic and ophthalmic drugs can reduce occurrence risk. Clinical practitioners should be vigilant and inform patients of these risks.

Vapor Nucleation on Hybrid-Wetting Nanoconvex Surfaces: The Competition between Intrinsic Wettability and Topography.

Hybrid-wetting surfaces with hydrophilic spots reduced from the micrometer to nanometer scale have been confirmed to enhance vapor nucleation while simultaneously minimizing droplet pinning. Given that surface topography also plays a critical role in influencing nucleation characteristics, the effect of competition between intrinsic wettability and topography on nucleation remains unclear when both surface topography and hydrophilic regions approach the critical nucleation size. This work investigated vapor nucleation on two types of hybrid-wetting nanoconvex surfaces. On random hybrid-wetting convex surfaces, the most negative potential energy sites were located at the sides of the convex structures, leading vapor to preferentially nucleate at these locations, consistent with observations on homogeneous surfaces. Despite similar average potential energy values across the surface, wettability variations in hydrophilic and hydrophobic atoms significantly alter the surface energy distribution. As the wettability difference between hydrophilic and hydrophobic atoms increases, stronger hydrophilic atoms generate relatively higher local energy regions, promoting vapor rapid nucleation. The edge effect still exists at a hydrophilic atom ratio of 10%, and competition among hydrophilic spots impedes vapor nucleation and growth. However, when the ratio increases to 40%, the increased surface average potential energy promotes the probability of vapor contacting the surface, leading to rapid vapor nucleation on the sides of the convex structures. In addition, surface potential energy analysis and the Monte Carlo method revealed that nucleation locations on nanoconvex surfaces are governed by the competition between intrinsic wettability and topography. When the magnitude of the potential energy generated by the hydrophilic atoms exceeds that from the topography, stronger solid-liquid interactions at the top of the convex structure increase the likelihood of vapor contacting the surface, resulting in nucleation at the top. Conversely, when the magnitude of the potential energy generated by hydrophilic atoms is lower than that from topography, nucleation preferentially still occurs on the sides.

[Pollution Characteristics and Source Apportionment of Heavy Metals in Topsoil of Counties Along the Shandong Section of the Yellow River].

The 25 counties along the Shandong section of the Yellow River are the core areas for promoting the ecological protection and high-quality development of the Yellow River in Shandong Province. Moreover, it is of great significance to study the current situation, sources, and potential risks of heavy metal pollution in the topsoil in this region. In this study, 103 soil samples were collected from the 25 counties along the Shandong section of the Yellow River, and the contents of eight heavy metals （As, Cu, Pb, Cr, Zn, Ni, Cd, and Hg） were determined. The pollution characteristics of heavy metals were analyzed and evaluated using the geological accumulation index and potential ecological risk index. Correlation analysis and the positive matrix factorization （PMF） model were used to analyze the sources of heavy metals. The results showed that the average contents of Cu and Cr were lower than that of the background values of soils, whereas the average contents of As, Pb, Zn, Ni, Cd, and Hg were 1.16, 1.42, 1.05, 1.14, 2.29, and 1.85 times higher than that of the background values, respectively, and the average contents of all eight elements were lower than the screening value of soil pollution risk in agricultural land. In terms of different heavy metal variations, the coefficient of variation （CV） of Cu and Cd was higher than 0.500, indicating high variations, whereas As, Pb, Cr, Zn, Ni, and Hg showed moderate variation. Cd and Hg were slightly polluted, whereas the other six elements were not polluted. Cd and Hg had a moderate potential ecological risk level, whereas the other six elements were at a low level. Correlation analysis and PMF model showed that the sources of heavy metals in the study area were influenced by four factors, i.e., agricultural activities, natural sources, industrial emissions, and atmospheric dust from coal combustion and vehicle exhaust emissions, and the relative contribution rates were 32.4%, 34.9%, 16.5%, and 16.2%, respectively.