Crosstalk between DNA Damage Repair and Metabolic Regulation in Hematopoietic Stem Cells.

Self-renewal and differentiation are two characteristics of hematopoietic stem cells (HSCs). Under steady physiological conditions, most primitive HSCs remain quiescent in the bone marrow (BM). They respond to different stimuli to refresh the blood system. The transition from quiescence to activation is accompanied by major changes in metabolism, a fundamental cellular process in living organisms that produces or consumes energy. Cellular metabolism is now considered to be a key regulator of HSC maintenance. Interestingly, HSCs possess a distinct metabolic profile with a preference for glycolysis rather than oxidative phosphorylation (OXPHOS) for energy production. Byproducts from the cellular metabolism can also damage DNA. To counteract such insults, mammalian cells have evolved a complex and efficient DNA damage repair (DDR) system to eliminate various DNA lesions and guard genomic stability. Given the enormous regenerative potential coupled with the lifetime persistence of HSCs, tight control of HSC genome stability is essential. The intersection of DDR and the HSC metabolism has recently emerged as an area of intense research interest, unraveling the profound connections between genomic stability and cellular energetics. In this brief review, we delve into the interplay between DDR deficiency and the metabolic reprogramming of HSCs, shedding light on the dynamic relationship that governs the fate and functionality of these remarkable stem cells. Understanding the crosstalk between DDR and the cellular metabolism will open a new avenue of research designed to target these interacting pathways for improving HSC function and treating hematologic disorders.

Association between duration of antidepressant treatment for major depressive disorder and relapse rate after discontinuation: A meta-analysis.

The optimal duration of antidepressant treatment for patients with major depressive disorder to reduce the risk of relapse after discontinuation remains uncertain. Medline, Cochrane Central Register of Controlled Trials, and Embase were systematically searched for randomized controlled trials (RCTs) with a discontinuation design. A single-group summary meta-analysis was performed to calculate 6-month relapse rates after discontinuation. Meta-regression with restricted cubic splines was performed to model the non-linear relationship between treatment duration and relapse rate after discontinuation. Thirty-five RCTs were included. The relapse rate after discontinuation was approximately 34.81 % at 6 months and 45.12 % at 12 months. After controlling for covariates, the meta-analysis shows that the duration of treatment is associated with the risk of relapse after discontinuation in a non-linear curve, with a relatively higher risk of relapse observed for a duration of less than three months. There appears to be no further reduction in the risk of relapse when treatment is continued for over six months. Our results indicate the importance of at least three months of treatment to avoid the relatively high risk of relapse after discontinuation. The additional benefit of longer treatment remains to be proven.

Deep learning-based inverse design of multi-functional metasurface absorbers.

A novel approach-integrating a simulated annealing (SA) algorithm with deep learning (DL) acceleration-is presented for the rapid and accurate development of terahertz perfect absorbers through forward prediction and backward design. The forward neural network (FNN) effectively deduces the absorption spectrum based on metasurface geometry, resulting in an 80,000-fold increase in computational speed compared to a full-wave solver. Furthermore, the absorber's structure can be precisely and promptly derived from the desired response. The incorporation of the SA algorithm significantly enhances design efficiency. We successfully designed low-frequency, high-frequency, and broadband absorbers spanning the 4 to 16 THz range with an error margin below 0.02 and a remarkably short design time of only 10 min. Additionally, the proposed model in this Letter introduces a novel, to our knowledge, method for metasurface design at terahertz frequencies such as the design of metamaterials across optical, thermal, and mechanical domains.

Occurrence of Cassava (Manihot esculenta) Leaf Spot Disease Caused by Diaporthe ueckeri in China.

Cassava (Manihot esculenta) is a perennial crop of the family Euphorbiaceae, widely cultivated due to its phytopharmacological and economic values in China. In November 2022, a leaf spot disease on cassava was observed in Zhanjiang, Guangdong, China (21.17° N, 110.18° E), with 100% disease incidence. About 80 % of leaves were covered with spots on the infected plants. Typical symptoms initially appeared as irregular water-soaked lesions that became brown and whitish with the progress of the disease, lesions gradually expanded and coalesced, causing leaf withering, drying and final fall. Tissues (4 to 5 mm) were excised from the margin of lesions, sterilized in 3% H2O2 solution for 3 min, rinsed three times with sterile water, placed on potato dextrose agar (PDA) medium (containing 50mg/L penicillin), and incubated at 25-28 °C. Ten single hypha isolates with similar morphology were obtained and further purified as single conidium subcultures. The colony was grey whitish with sparse aerial mycelium and colony diameter reached 70.4 mm after four days incubation at 25-28℃ in the dark. Black pycnidia occurring as clusters were spherical or irregular, erumpent at maturity, often with a creamy whitish, conidial cirrus extruding from ostiole after 30-days incubation. Conidiophores were hyaline, smooth, unbranched. Alpha conidia were bi-guttulate, hyaline, ellipsoidal, aseptate, with dimensions of 5.1~7.5×1.9~3.4µm (mean 6.2×2.8 µm, n>50). Beta conidia were abundant, filiform, hyaline, smooth, curved in a hooked shape, with a truncate base and dimensions of 18.5-26.4 × 0.6-1.2µm (mean 23.4 × 1.0 µm, n= 40) . Gamma conidia were not observed. The morphological characteristics were similar to those of Diaporthe ueckeri (Udayanga et al. 2015). The internal transcribed spacer (ITS) region, large subunit (LSU) rRNA sequence, actin (ACT), calmodulin (CAL), histone H3 (HIS), translation elongation factor 1-alpha (TEF1-α), and ß-tubulin (TUB) genes of a representative isolate CCAS-MS-6 (ACCC 35497) were amplified and sequenced using primer pairs: ITS5/ITS4, LR0R/LR5, ACT-512F/ACT-783R, CAL228F/CAL737R, CYLH3F/ H3-1b, EF1-728F/ EF1-986R and Bt2a/Bt2b (Gao et al 2017；Udayanga et al 2014). All sequences were deposited in GenBank (OR361671, OR361672, and OR365605-9). BLAST search showed high similarities with sequences of Diaporthe ueckeri (Tab 1). Maximum likelihood analyses of the concatenated data of CAL, HIS, ITS, TEF and TUB using Mega 11 placed CCAS-MS-6 in the D. ueckeri clade. Thus, the fungus was identified as D. ueckeri. Three one-year old healthy plants were used for pathogenicity tests in pots. Two 15-day old leaves of each plant were cleaned with 75% alcohol, three sites on each leaf were wounded, and sites on one of the leaf were covered with fungal plugs from 15-day-old cultures on PDA, and sites on the other leaf with PDA plugs as a control. All plants were kept at ambient temperature (about 28℃) and covered with plastic bags containing sterile wet cotton to maintain the humidity. Seven days after inoculation, all inoculated sites showed symptoms of necrosis, while control sites showed no symptoms. The same fungus identified on the basis of morphological and molecular criteria was reisolated from symptomatic inoculated leaves. In China, D. ueckeri had been reported to cause diseases on Eucalyptus citriodora, Camellia sinensis, and Michelia shiluensis (Gao et al 2016; Liao et al 2023; Yi et al 2018), this is the first report on M. esculenta. The definition of the disease etiology is a prerequisite to develop effective management strategies.

Circular RNA circESYT2 serves as a microRNA-665 sponge to promote the progression of hepatocellular carcinoma through ENO2.

Circular RNAs (circRNAs) have emerged as crucial regulators in tumor progression, yet their specific role in hepatocellular carcinoma (HCC) remains largely uncharacterized. In this study, we utilized high-transcriptome sequencing to identify the upregulation of circESYT2 (hsa_circ_002142) in HCC tissues. Functional experiments carried out in vivo and in vitro revealed that circESYT2 played a significant role in maintaining the growth and metastatic behaviors of HCC. Through integrative analysis, we identified enolase 2 (ENO2) as a potential target regulated by circESYT2 through the competitive endogenous RNA sponge mechanism. Additional gain- or loss-of-function experiments indicated that overexpression of circESYT2 led to a tumor-promoting effect, which could be reversed by transfection of microRNA-665 (miR-665) mimic or ENO2 knockdown in HCC cells. Furthermore, the direct interaction between miR-665 and circESYT2 and between miR-665 and ENO2 was confirmed using RNA immunoprecipitation, FISH, RNA pull-down, and dual-luciferase reporter assays, highlighting the involvement of the circESYT2/miR-665/ENO2 axis in promoting HCC progression. These findings shed light on the molecular characteristics of circESYT2 in HCC tissues and suggest its potential as a biomarker or therapeutic target for HCC treatment.

HES6: an emerging player in human hematopoiesis.

Not available.

Enhancing antibacterial properties by regulating valence configurations of copper: a focus on Cu-carboxyl chelates.

Optimizing the antibacterial effectiveness of copper ions while reducing environmental and cellular toxicity is essential for public health. A copper chelate, named PAI-Cu, is skillfully created using a specially designed carboxyl copolymer (a combination of acrylic and itaconic acids) with copper ions. PAI-Cu demonstrates a broad-spectrum antibacterial capability both in vitro and in vivo, without causing obvious cytotoxic effects. When compared to free copper ions, PAI-Cu displays markedly enhanced antibacterial potency, being about 35 times more effective against Escherichia coli and 16 times more effective against Staphylococcus aureus. Moreover, Gaussian and ab initio molecular dynamics (AIMD) analyses reveal that Cu+ ions can remain stable in the carboxyl compound's aqueous environment. Thus, the superior antibacterial performance of PAI-Cu largely stems from its modulation of copper ions between mono- and divalent states within the Cu-carboxyl chelates, especially via the carboxyl ligand. This modulation leads to the generation of reactive oxygen species (˙OH), which is pivotal in bacterial eradication. This research offers a cost-effective strategy for amplifying the antibacterial properties of Cu ions, paving new paths for utilizing copper ions in advanced antibacterial applications.

Biomass power generation: A pathway to carbon neutrality.

In light of the pressing need to reduce carbon emissions, the biomass power generation industry has gained significant attention and has increasingly become a crucial focus in China. However, there are still considerable gaps in the historical background, status, and prospects of biomass power generation. Herein, the historical and current states of biomass power generation in China are systematically reviewed, with a particular emphasis on supporting policies, environmental impacts, and future projections. By 2022, the newly installed capacity for biomass power generation reached 3.34 MW with a total installed capacity of 41 MW. The power produced from biomass power generation is 182.4 billion kWh in China. The total installed capacity and generated power in 2022 were 1652 and 1139 folds higher than in 2006 when the first biomass generation plant was established. However, disparities in the distributions of biomass resources and power generation were observed. Key drivers of the industry development include tax, finance, and subsidy policies. Under the implementation of the 14th Five-Year Plan for renewable energy development and the goal of carbon neutrality, biomass power generation may achieve great success through more target policy support and advanced technologies reducing air pollutants emissions. If combined with Bioenergy with carbon capture and storage (BECCS) technology, biomass power generation will make its contribution to carbon neutrality in China.

Keplerate-Type Polyoxometalates-Based Triboelectric Nanogenerator for Higher Performance via the Morphology Modulation of Blackberry Structure.

The triboelectric material is the key factor affecting the performance of triboelectric nanogenerators (TENGs). Inorganic materials have higher heat resistance and stability than widely used organic materials. However, the weaker triboelectric property limits the application of TENGs. Modulating surface roughness by changing particle shape and size is a simple way to increase performance for TENGs. Polyoxometalates (POMs) have unrivalled structural diversity and can self-assemble to form different nanostructures. In this study, we propose [{(NH4)42[Mo72VIMo60VO372(CH3COO)30(H2O)7.ca.300H2O.ca.CH3COONH4)]}-Mo132] and [{Na8K14(VO)2[{(MoVI)(Mo5VIO21)(H2O)3]}10{(MoVI)Mo5VIO21(H2O)3(SO4)}2{VIVO(H2O)20}{VIVO}10({KSO4}5)2]·150H2O)}-Mo72V30] with blackberry structure which are cured and prepared into film by spin-coating technique, are used as triboelectric positive materials for the first time in the field of TENGs. Keplerate-type polyoxometalates can form blackberry structures with higher dispersibility and flexibility, which can be used to control surface roughness by regulating the size of particles. The discovery proves that the particle size influences the surface roughness, which adjusts the output of TENGs. According to our findings, Mo132-h-TENG generates an output voltage of 29.3 V, an output charge of 8 nC 2-3 folds higher than Mo132-TENG, and a maximum power density of 6.25 mW·m-2 at 300 MΩ. Our research provides that altering the dimensional size can be an available way to raise the output of TENGs.

Construct Phenylethanoid Glycosides Harnessing Biosynthetic Networks, Protein Engineering and One-Pot Multienzyme Cascades.

Phenylethanoid glycosides (PhGs) exhibit a multitude of structural variations linked to diverse pharmacological activities. Assembling various PhGs via multienzyme cascades represents a concise strategy over traditional synthetic methods. However, the challenge lies in identifying a comprehensive set of catalytic enzymes. This study explores biosynthetic PhG reconstruction from natural precursors, aiming to replicate and amplify their structural diversity. We discovered 12 catalytic enzymes, including four novel 6'-OH glycosyltransferases and three new polyphenol oxidases, revealing the intricate network in PhG biosynthesis. Subsequently, the crystal structure of CmGT3 (2.62 Å) was obtained, guiding the identification of conserved residue 144# as a critical determinant for sugar donor specificity. Engineering this residue in PhG glycosyltransferases (FsGT61, CmGT3, and FsGT6) altered their sugar donor recognition. Finally, a one-pot multienzyme cascade was established, where the combined action of glycosyltransferases and acyltransferases boosted conversion rates by up to 12.6-fold. This cascade facilitated the reconstruction of 26 PhGs with conversion rates ranging from 5-100 %, and 20 additional PhGs detectable by mass spectrometry. PhGs with extra glycosyl and hydroxyl modules demonstrated notable liver cell protection. This work not only provides catalytic tools for PhG biosynthesis, but also serves as a proof-of-concept for cell-free enzymatic construction of diverse natural products.

Centrifugo-Pneumatic Reciprocating Flowing Coupled with a Spatial Confinement Strategy for an Ultrafast Multiplexed Immunoassay.

Immunoassays serve as powerful diagnostic tools for early disease screening, process monitoring, and precision treatment. However, the current methods are limited by high costs, prolonged processing times (>2 h), and operational complexities that hinder their widespread application in point-of-care testing. Here, we propose a novel centrifugo-pneumatic reciprocating flowing coupled with spatial confinement strategy, termed PRCM, for ultrafast multiplexed immunoassay of pathogens on a centrifugal microfluidic platform. Each chip consists of four replicated units; each unit allows simultaneous detection of three targets, thereby facilitating high-throughput parallel analysis of multiple targets. The PRCM platform enables sequential execution of critical steps such as solution mixing, reaction, and drainage by coordinating inherent parameters, including motor rotation speed, rotation direction, and acceleration/deceleration. By integrating centrifugal-mediated pneumatic reciprocating flow with spatial confinement strategies, we significantly reduce the duration of immune binding from 30 to 5 min, enabling completion of the entire testing process within 20 min. As proof of concept, we conducted a simultaneous comparative test on- and off-the-microfluidics using 12 negative and positive clinical samples. The outcomes yielded 100% accuracy in detecting the presence or absence of the SARS-CoV-2 virus, thus highlighting the potential of our PRCM system for multiplexed point-of-care immunoassays.

Co-assisted strategy of sacrificial salt-template and nitrogen-doping to promote lithium storage performance of NiO-Ni/N-C frameworks.

Tailoring the omnidirectional conductivity networks in nickel oxide-based electrodes is important for ensuring their long lifespan, stability, high capacity, and high-rate capability. In this study, nickel metal nanoparticles and a three-dimensional nitrogen-doped carbon matrix were used to embellish the nickel oxide composite NiO-Ni/N-C via simplified hard templating. When a porous nitrogen-doped carbon matrix is present, a rapid pathway would be established for charging and discharging the electrons and lithium ions in a lithium-ion battery, thereby alleviating the volumetric expansion of the NiO nanoparticles during the operation of the battery. Moreover, the Ni0 ions added to serve as active sites to improve the capacity of the NiO-based electrodes and strengthen their conductivities. The multielement-effects of the optimal NiO-Ni/N-C electrode leads it to exhibit a capacity of 1310.8 mAh g-1 at 0.1 A g-1 for 120 loops and a rate capability of 441.5 mAh g-1 at 20.0 A g-1. Kinetic analysis of the prepared electrodes proved their ultrafast ionic and electronic conductivities. This strategy of hard templating reduces the number of routes required for preparing different types of electrodes, including NiO-based electrodes, and improves their electrochemical performance to enable their use in energy storage applications.

Efficacy and safety of a "radical" surgical strategy in the treatment of parasagittal sinus meningioma.

Background: No standardized criteria for surgical resection of parasagittal sinus meningiomas (PSM) have been established, and different surgical strategies have been proposed. The aim of the present study was to investigate the efficacy and safety of a "radical" surgical strategy in the treatment of PSM. Methods: The clinical histories, radiological findings, pathologic features, and surgical records of 53 patients with PSM admitted by the same surgical team using the "radical" surgical strategy were retrospectively analyzed between 2018 and 2023. Results: Among the 53 PSM cases, 16 (30.2%) had a patent sinus proper, 28 (52.8%) had partial obstruction of the sinus proper, and 9 (17.0%) had complete obstruction of the sinus proper before the operation. During operation, Simpson grade I resection was performed in 34 (64.2%) cases and Simpson grade II in 19 (35.8%) cases. Postoperative pathologic examination suggested tumors of WHO grade I in 47 (88.7%) cases, WHO grade II in 4 (7.5%) cases, and WHO grade III in 2 (3.8%) cases. Postoperative complications primarily included a small amount of delayed intracerebral hemorrhage in 3 (5.7%) cases, exacerbation of cerebral edema in 3 (5.7%) cases, exacerbation of motor and sensory deficits in 4 (7.5%) cases, and intracranial infection in 2 (3.8%) cases. There were no cases of death or new-onset neurological dysfunction. Dizziness and headache symptoms improved to varying degrees, and a seizure-free status was achieved postoperatively. Excluding one case lost to follow-up, the average follow-up period was 33 months, and there were no cases of recurrence. Conclusion: A "radical" strategy for the surgical management of PSM is effective, safe, and simple to perform, provided that the sagittal sinus is properly managed and its associated veins are protected.

Redox-active NiS@bacterial cellulose nanofiber composite separators with superior rate capability for lithium-ion batteries.

Separator is an essential component of lithium-ion batteries (LIBs), which is placed between the electrodes to impede their electrical contact and provide the transport channels for lithium ions. Traditionally, the separator contributes the overall mass of LIBs, thereby reducing the gravimetric capacity of the devices. Herein, a dual-layer redox-active cellulose separator is designed and fabricated to enhance the electrochemical performances of LIBs by introducing NiS. The presented separator is composed of an insulating bacterial cellulose (BC) nanofiber layer and a conductive, and redox-active NiS@BC/carbon nanotubes layer. By using the NiS@BC separator, the discharge capacity of the LiFePO4//Li half battery is enhanced to 117 mAh g-1 at a current of 2C owing to the redox-activity of NiS. Moreover, the functional separator-electrode interface can facilitate the homogenous Li stripping/plating and depress the polarization upon the repeated stripping/plating process. Consequently, the battery containing the redox-active separator exhibits outstanding cycle stability and rate capability. The present study contributes a novel strategy for the developments of functional separators to improve the electrochemical properties of LIBs.

PVDF/ZnO piezoelectric nanofibers designed for monitoring of internal micro-pressure.

Organic piezoelectric materials are emerging as integral components in the development of advanced implantable self-powered sensors for the next generation. Despite their promising applications, a key limitation lies in their reduced mechanical force-to-electricity conversion efficiency. In this study, we present a breakthrough in the fabrication of soft poly(vinylidene fluoride) (PVDF) organic electrospun piezoelectric nanofibers (OEPNs) with exceptional piezoelectric performance achieved through the incorporation of zinc oxide nanorods (ZnO NR). The inclusion of ZnO NR proved instrumental in augmenting the nanocrystallization of PVDF organic electrospun piezoelectric nanofibers (OEPNs), leading to a highly efficient crystal phase transformation from the α phase to the ß/γ phase, serving as superior piezoelectric working dipoles. The resulting PVDF/ZnO NR OEPNs exhibited unparalleled piezoelectric output voltage and current density, particularly noteworthy under a micro-pressure of 1 kPa and a low frequency of 1.5 Hz. Utilizing the obtained PVDF/ZnO NR OEPNs as the piezoelectric working element, we engineered a soft self-powered micro-pressure sensor. This sensor was implanted simultaneously on the cardiovascular walls of the heart and femoral artery in pigs. The sensor demonstrated precise monitoring and recording capabilities for micro-pressure changes during various physiological states, spanning from wakefulness to coma, euthanasia, and notably, the formation of cardiac thrombus. These findings underscore the immense potential of the implantable self-powered sensor for the assessment and diagnosis of pressure-related cardiovascular diseases, such as thrombus and atherosclerosis, during the postoperative recovery phase. This innovative technology offers valuable insights into the dynamic physiological states, paving the way for enhanced postoperative care and management of cardiovascular conditions.

Systematically quantifying the dynamic characteristics of PM2.5 in multiple indoor environments in a plateau city: Implication for internal contribution.

People generally spend most of their time indoors, making a comprehensive evaluation of air pollution characteristics in various indoor microenvironments of great significance for accurate exposure estimation. In this study, field measurements were conducted in Kunming City, Southwest China, using real-time PM2.5 sensors to characterize indoor PM2.5 in ten different microenvironments including three restaurants, four public places, and three household settings. Results showed that the daily average PM2.5 concentrations in restaurants, public spaces, and households were 78.4 ± 24.3, 20.1 ± 6.6, and 18.0 ± 4.3 µg/m3, respectively. The highest levels of indoor PM2.5 in restaurants were owing to strong internal emissions from cooking activities. Dynamic changes showed that indoor PM2.5 levels increased during business time in restaurants and public places, and cooking time in residential kitchens. Compared with public places, restaurants generally exhibit more rapid increases in indoor PM2.5 due to cooking activities, which can elevate indoor PM2.5 to high levels (5.1 times higher than the baseline) in a short time. Furthermore, indoor PM2.5 in restaurants were dominated by internal emissions, while outdoor penetration contributed mostly to indoor PM2.5 in public places and household settings. Results from this study revealed large variations in indoor PM2.5 in different microenvironments, and suggested site-specific measures for indoor PM2.5 pollution alleviation.

In Situ Loading of Ni3ZnC0.7 Nanoparticles with Carbon Nanotubes to 3D Melamine Sponge Derived Hollow Carbon Skeleton toward Superior Microwave Absorption and Thermal Resistance.

The simple and low-cost construction of a 3D network structure is an ideal way to prepare high-performance electromagnetic wave (EMW) absorption materials. Herein, a series of carbon skeleton/carbon nanotubes/Ni3ZnC0.7 composites (CS/CNTs/Ni3ZnC0.7) are successfully prepared by in situ growth of Ni3ZnC0.7 and CNTs on 3D melamine sponge carbon. With the increase of precursor, Ni3ZnC0.7 nanoparticles nucleate and catalyze the generation of CNTs on the surface of the carbon skeleton. The minimum reflection loss (RL) value of the S60min composite (loading time of 60 min) reaches -86.6 dB at 1.6 mm and effective absorption bandwidth (EAB, RL≤-10 dB) is up to 9.3 GHz (8.7-18 GHz). The 3D network sponge carbon with layered micro/nanostructure and hollow skeleton promotes multiple reflection and absorption mechanisms of incident EMW. The N-doping and defects can be equivalent to an electric dipole, providing dipole polarization to increase dielectric relaxation. The uniform Ni3ZnC0.7 nanoparticles and CNTs play a key role in dissipating electromagnetic energy, blocking heat transfer, and enhancing the mechanical properties of the skeleton. Fortunately, the composite displays a quite low thermal conductivity of 0.09075 W m·K-1 and good flexibility, which can provide insulation and quickly recover to its original state after being stressed.

Genetic correlation between circulating metabolites and chalazion: a two-sample Mendelian randomization study.

Background: Lipid metabolism disorders were observationally associated with chalazion, but the causality of the related circulating metabolites on chalazion remained unknown. Here, we investigated the potential causal relationship between circulating metabolites and chalazion using two-sample Mendelian randomization (MR) analysis. Methods: For the primary analysis, 249 metabolic biomarkers were obtained from the UK Biobank, and 123 circulating metabolites were obtained from the publication by Kuttunen et al. for the secondary analysis. Chalazion summary data were obtained from the FinnGen database. Inverse variance weighted (IVW) is the main MR analysis method, and the MR assumptions were evaluated in sensitivity and colocalization analyses. Results: Two MR analyses results showed that the common metabolite, alanine, exhibited a genetic protective effect against chalazion (primary analysis: odds ratio [OR] = 0.680; 95% confidence interval [CI], 0.507-0.912; p = 0.010; secondary analysis: OR = 0.578; 95% CI, 0.439-0.759; p = 0.00008). The robustness of the findings was supported by heterogeneity and horizontal pleiotropy analysis. Two colocalization analyses showed that alanine did not share a region of genetic variation with chalazion (primary analysis: PPH4 = 1.95%; secondary analysis: PPH4 = 25.3%). Moreover, previous studies have suggested that an increase in the degree of unsaturation is associated with an elevated risk of chalazion (OR = 1.216; 95% CI, 1.055-1.401; p = 0.007), with omega-3 fatty acids (OR = 1.204; 95% CI, 1.054-1.377; p = 0.006) appearing to be the major contributing factor, as opposed to omega-6 fatty acids (OR = 0.850; 95% CI, 0.735-0.982; p = 0.027). Conclusion: This study suggests that alanine and several unsaturated fatty acids are candidate molecules for mechanistic exploration and drug target selection in chalazion.

XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial.

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6-18.0) for the immunotherapy group compared with 9.9 months (8.0-11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40-0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3-32.8) for the control group (HR, 0.57 [95% CI, 0.33-0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

LiViT-Net: A U-Net-like, lightweight Transformer network for retinal vessel segmentation.

The intricate task of precisely segmenting retinal vessels from images, which is critical for diagnosing various eye diseases, presents significant challenges for models due to factors such as scale variation, complex anatomical patterns, low contrast, and limitations in training data. Building on these challenges, we offer novel contributions spanning model architecture, loss function design, robustness, and real-time efficacy. To comprehensively address these challenges, a new U-Net-like, lightweight Transformer network for retinal vessel segmentation is presented. By integrating MobileViT+ and a novel local representation in the encoder, our design emphasizes lightweight processing while capturing intricate image structures, enhancing vessel edge precision. A novel joint loss is designed, leveraging the characteristics of weighted cross-entropy and Dice loss to effectively guide the model through the task's challenges, such as foreground-background imbalance and intricate vascular structures. Exhaustive experiments were performed on three prominent retinal image databases. The results underscore the robustness and generalizability of the proposed LiViT-Net, which outperforms other methods in complex scenarios, especially in intricate environments with fine vessels or vessel edges. Importantly, optimized for efficiency, LiViT-Net excels on devices with constrained computational power, as evidenced by its fast performance. To demonstrate the model proposed in this study, a freely accessible and interactive website was established (https://hz-t3.matpool.com:28765?token=aQjYR4hqMI), revealing real-time performance with no login requirements.