Electroacupuncture Alleviates Memory Deficits in APP/PS1 Mice by Targeting Serotonergic Neurons in Dorsal Raphe Nucleus.

OBJECTIVE: Alzheimer's disease (AD) has become a significant global concern, but effective drugs able to slow down AD progression is still lacked. Electroacupuncture (EA) has been demonstrated to ameliorate cognitive impairment in individuals with AD. However, the underlying mechanisms remains poorly understood. This study aimed at examining the neuroprotective properties of EA and its potential mechanism of action against AD. METHODS: APP/PS1 transgenic mice were employed to evaluate the protective effects of EA on Shenshu (BL 23) and Baihui (GV 20). Chemogenetic manipulation was used to activate or inhibit serotonergic neurons within the dorsal raphe nucleus (DRN). Learning and memory abilities were assessed by the novel object recognition and Morris water maze tests. Golgi staining, western blot, and immunostaining were utilized to determine EA-induced neuroprotection. RESULTS: EA at Shenshu (BL 23) and Baihui (GV 20) effectively ameliorated learning and memory impairments in APP/PS1 mice. EA attenuated dendritic spine loss, increased the expression levels of PSD95, synaptophysin, and brain-derived neurotrophic factor in hippocampus. Activation of serotonergic neurons within the DRN can ameliorate cognitive deficits in AD by activating glutamatergic neurons mediated by 5-HT1B. Chemogenetic inhibition of serotonergic neurons in the DRN reversed the effects of EA on synaptic plasticity and memory. CONCLUSION: EA can alleviate cognitive dysfunction in APP/PS1 mice by activating serotonergic neurons in the DRN. Further study is necessary to better understand how the serotonergic neurons-related neural circuits involves in EA-induced memory improvement in AD.

Voltage control of multiferroic magnon torque for reconfigurable logic-in-memory.

Magnons, bosonic quasiparticles carrying angular momentum, can flow through insulators for information transmission with minimal power dissipation. However, it remains challenging to develop a magnon-based logic due to the lack of efficient electrical manipulation of magnon transport. Here we show the electric excitation and control of multiferroic magnon modes in a spin-source/multiferroic/ferromagnet structure. We demonstrate that the ferroelectric polarization can electrically modulate the magnon-mediated spin-orbit torque by controlling the non-collinear antiferromagnetic structure in multiferroic bismuth ferrite thin films with coupled antiferromagnetic and ferroelectric orders. In this multiferroic magnon torque device, magnon information is encoded to ferromagnetic bits by the magnon-mediated spin torque. By manipulating the two coupled non-volatile state variables-ferroelectric polarization and magnetization-we further present reconfigurable logic operations in a single device. Our findings highlight the potential of multiferroics for controlling magnon information transport and offer a pathway towards room-temperature voltage-controlled, low-power, scalable magnonics for in-memory computing.

The photothermal effect of intense pulsed light and LipiFlow in eyelid related ocular surface diseases: Meibomian gland dysfunction, Demodex and blepharitis.

The treatment and management of ocular surface diseases have shifted towards a co-treatment approach focusing on overall ocular surface homeostasis. When treating issues related to the eye, it is essential to not only focus on the damaged or disabled areas but also consider the larger picture. Meibomian gland dysfunction (MGD), Demodex infection, and blepharitis all interact at the eyelid site and can cause damage to the ocular surface to varying degrees. Palpebral lesions disrupt the balance of ocular surface homeostasis, leading to dry eye and keratitis. Traditional treatments, such as manual physical hot compress massage, have limited effectiveness due to the structure of the eyelid. However, intense pulsed light (IPL) technology uses penetrating light energy to generate heat energy, which can eliminate inflammation of capillaries or kill Demodex. Additionally, the LipiFlow thermal effect and physical compression provide a more vital and longer-lasting therapeutic effect on MGD by excluding other primary causes of ocular surface inflammation. Therefore, personalized treatment techniques based on photothermal effects may be effective. In the future, IPL and LipiFlow may potentially dismiss immune-inflammation factors causing ocular surface disease or block the delivery of systemic immune-related diseases.

Simultaneous efficient removal of tetracycline and mitigation of antibiotic resistance genes enrichment by a modified activated sludge process with static magnetic field.

To address the increasing issue of antibiotic wastewater, this study applied a static magnetic field (SMF) to the activated sludge process to increase the efficiency of tetracycline (TC) removal from swine wastewater and to reveal its enhanced mechanisms. The results demonstrated that the SMF-modified activated sludge process could achieve almost complete TC removal at sludge loading rates of 0.3 mg TC/g MLSS/d. Analysis of zeta potential and extracellular polymeric substances composition of the activated sludge revealed that SMF increased electrostatic interactions between TC and activated sludge and made activated sludge has much more binding sites, finally resulting in the increased TC biosorption. Metagenomic analysis showed that SMF promoted the enrichment of ammonia-oxidizing bacteria, TC-degrading bacteria, and aromatic compounds-degrading bacteria; it also enhanced ammonia monooxygenase- and cytochrome P450-mediated TC metabolism while upregulating functional genes associated with oxidase, reductase, and dehydrogenase - all contributing to increased TC biodegradation. Additionally, SMF mitigated the enrichment and spread of antibiotic resistance genes (ARGs) by decreasing the abundance of potential hosts of ARGs and inhibiting the upregulation of genes encoding ABC transporters and putative transposase. Based on these findings, this study demonstrates that magnetic field is an enhancement strategy with great potential to relieve the harmful impacts of the growing antibiotic wastewater problem on human health and the ecosystem.

Self-Assembled Mesoporous Silica Decorated with Biogenic Carbon Dot Nanospheres Hybrid Nanomaterial for Efficient Removal of Aqueous Methoxy-DDT Via a Short Bed Adsorption Column Technique.

Methoxy-DDT is an organochlorine pesticide extensively used in agricultural practices as a DDT substitute. Methoxy-DDT has been found and quantified in several investigations in groundwater, drinking water, sediment, and various biota. Therefore, designing efficient and cost-effective adsorbents for removing methoxy-DDT is vital. In this work, we embedded Ficus benghalensis L. derived carbon dots (CDs) in mesoporous silica (MS) to fabricate MS-CDs nanohybrid material. MS-CDs nanohybrid exhibited remarkable selectivity and removal efficiency towards methoxy-DDT, outperforming other endocrine disruptors. Parameters for industrial-scale fixed-bed adsorption columns, such as bed capacity, length, and breakthrough times, were analyzed. The kinetic study revealed that pseudo-second-order (PSO) adsorption and isotherm analysis confirmed the Langmuir model as the best fit. Small bed adsorption (SBA) column analysis was carried out using spiked Yamuna river water, and the breakthrough curves were demonstrated by varying MS-CDs bed height. The maximum adsorption capacity obtained for methoxy-DDT was 17.16 mg/g at breakthrough and 49.98 mg/g at exhaustion. The adsorbent showed 86.53% removal efficiency in the 5th cycle, demonstrating good reusability. These results indicate that the developed material MS-CDs-based organic sphere is an effective adsorbent for aqueous methoxy-DDT adsorption and can be applied to wastewater treatment.

High-Entropy Design for 2D Halide Perovskite.

Hybrid halide perovskites are good candidates for a range of functional materials such as optical electronic and photovoltaic devices due to their tunable band gaps, long carrier diffusion lengths, and solution processability. However, the instability in moisture/air, the toxicity of lead, and rigorous reaction setup or complex postprocessing have long been the bottlenecks for practical application. Herein, we present a simultaneous configurational entropy design at A-sites, B-sites, and X-sites in the typical (CHA)2PbBr4 two-dimensional (2D) hybrid perovskite. Our results demonstrate that the high-entropy effect favors the stabilization of the hybrid perovskite phase and facilitates a simple crystallization process without precise control of the cooling rate to prepare regular crystals. Moreover, high-entropy 2D perovskite crystals exhibit tunable energy band gaps, broadband emission, and a long carrier lifetime. Meanwhile, the high-entropy composition almost maintains the initial crystal structure in deionized water for 18 h while the original (CHA)2PbBr4 crystal mostly decomposes, suggesting obviously improved humidity stability. This work offers a facile approach to synthesize humidity-stable hybrid perovskites under mild conditions, accelerating relevant preparation of optoelectronics and light-emitting devices and facilitating the ultimate commercialization of halide perovskite.

Learning curve and initial outcomes of a novel percutaneously endoscopic-assisted total hip arthroplasty through mini bikini direct anterior approach: an observational cohort study.

OBJECTIVE: Although the direct anterior approach can reduce muscle damage and ensure accurate prosthesis placement, the steep learning curve and increased risk of complications associated with DAA necessitate careful consideration. Therefore, we describe a technique for a novel percutaneously endoscopic-assisted total hip arthroplasty through mini bikini direct anterior approach (mDAA) and report the learning curve and initial outcomes. METHODS: The first 125 THA performed by a single surgeon between September 2020 and February 2022 using the anterior approach were included, comprising the initial 41 cases of bikini DAA (bDAA) and the subsequent 84 cases of mDAA. Outcome measures included perioperative outcomes and postoperative complications. The cumulative sum analysis (CUSUM) was used to determine the learning curve of anterior approach THA for each patient's ORT. Multivariable analysis was performed to determine risk correlation. RESULTS: A total of 125 anterior approach THA completed between 2020 and 2022 were identified. Among these, 41 were performed via bDAA and 84 via mDAA. No statistically significant differences were observed between the groups in terms of age, gender distribution, BMI or follow-up time. A significant reduction in ORT was noted, from 140 min for bDAA to 130 min for mDAA. Furthermore, there was a consistent decrease in LOI, LOS, and wound-healing problems. There was no statistically significant difference between groups with respect to Harris Hip Scores and other postoperative complications. The curve inflection points of the learning curve for the bDAA and mDAA group were located in the 22nd and 68th cases, respectively. The reduction of hemoglobin indicated a predicted increase in ORT. CONCLUSIONS: In this study, ORT, LOI, LOS, and wound-healing problems decreased overall in mDAA group. After mastering the bDAA technique, approximately 27 mDAA cases are needed to acquire proficiency in this technique. Hence, mDAA is a valuable alternative for those seeking smaller incisions, resolving wound healing problems, and aiming for enhanced recovery after surgery.

Association between composite dietary antioxidant index and hyperlipidemia: a cross-sectional study from NHANES (2005-2020).

The association between the composite dietary antioxidant index (CDAI) and hyperlipidemia remains unclear. Therefore, this study aimed to investigate the relationship between CDAI and hyperlipidemia. The data used in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) dataset spanning from 2005 to 2020. Based on 24-h dietary recall interviews, the CDAI was calculated using the intake of six dietary antioxidants. Univariate and multivariate logistic regression models were employed to investigate the relationship between CDAI and the occurrence of hyperlipidemia. Additionally, restricted cubic spline (RCS) analysis was utilized to investigate potential non-linear relationships between the CDAI and risk of hyperlipidemia. The final analysis included 30,788 adults in the United States, among whom 25,525 (82.91%) were diagnosed with hyperlipidemia. A significant negative correlation was observed between the CDAI and hyperlipidemia in the unadjusted (Odds ratio [OR] 0.97 [95% CI 0.96, 0.98]) and multi-variable adjusted (OR 0.98 [95% CI 0.97, 0.99]) models. When the CDAI values were analyzed as a categorical variable, individuals in the highest quartile (OR 0.82 [95% CI 0.73, 0.92]) exhibited a nearly one fifth decreased risk of hyperlipidemia compared to those in the lowest quartile. Additionally, RCS analysis revealed a linear relationship between CDAI and hyperlipidemia (P for nonlinearity = 0.124). The results remained consistent across subgroups except for individuals under the age of 60 or those with diabetes mellitus. There was a significant negative correlation between the CDAI and risk of hyperlipidemia, indicating that maintaining an optimal CDAI level could effectively reduce the incidence of hyperlipidemia.

ATP6V0A1-dependent cholesterol absorption in colorectal cancer cells triggers immunosuppressive signaling to inactivate memory CD8+ T cells.

Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-ß1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-ß1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8+ T cells, ultimately suppressing their anti-tumor activities. Moreover, we identify daclatasvir, a clinically used anti-hepatitis C virus (HCV) drug, as an ATP6V0A1 inhibitor that can effectively enhance the memory CD8+ T cell activity and suppress tumor growth in CRC. These findings shed light on the potential for ATP6V0A1-targeted immunotherapy in CRC.

A high-quality chromosome-level genome assembly of the endangered tree Kmeria septentrionalis.

Kmeria septentrionalis is a critically endangered tree endemic to Guangxi, China, and is listed on the International Union for Conservation of Nature's Red List. The lack of genetic information and high-quality genome data has hindered conservation efforts and studies on this species. In this study, we present a chromosome-level genome assembly of K. septentrionalis. The genome was initially assembled to be 2.57 Gb, with a contig N50 of 11.93 Mb. Hi-C guided genome assembly allowed us to anchor 98.83% of the total length of the initial contigs onto 19 pseudochromosomes, resulting in a scaffold N50 of 135.08 Mb. The final chromosome-level genome, spaning 2.54 Gb, achieved a BUSCO completeness of 98.9% and contained 1.67 Gb repetitive elements and 35,927 coding genes. This high-quality genome assembly provides a valuable resource for understanding the genetic basis of conservation-related traits and biological properties of this endangered tree species. Furthermore, it lays a critical foundation for evolutionary studies within the Magnoliaceae family.

Impact of nitric oxide via cardiopulmonary bypass on pediatric heart surgery: a meta-analysis of randomized controlled trials.

OBJECTIVE: The impact of nitric oxide (NO) administered via cardiopulmonary bypass (CPB) on pediatric heart surgery remains controversial. The objective of this study is to conduct a comprehensive systematic review and meta-analysis to examine the impact of NO administered via CPB on pediatric heart surgery. METHODS: This study searched 7 electronic databases to identify Randomized Controlled Trials (RCTs) on the impact of NO administration during CPB on postoperative outcomes in pediatric heart surgery. The searched databases included Embase, Medline (though PubMed), Cochrane Library, Web of Science, Wan Fang database, China National Knowledge Infrastructure (CNKI), and ClinicalTrials.gov from their inception to November 2, 2022. The included RCTs compared NO administration during CPB with standard CPB procedures or placebo gas treatment in pediatric heart surgery. fixed-effects models and/or random-effects models were used to estimate the effect size with 95% confidence interval (CI). Heterogeneity among studies was indicated by p-values and I2. All analyses were performed using Review Manager software (version 5.4) in this study. RESULTS: A total of 6 RCTs including 1,739 children were identified in this study. The primary outcome was duration of postoperative mechanical ventilation, with the length of hospital and intensive care unit (ICU) stay as the second outcomes. Through a pooled analysis, we found that exogenous NO administered via CPB for pediatric heart surgery could not shorten the duration of postoperative mechanical ventilation when compared with the control group (standardized mean difference (SMD) -0.07, CI [-0.16, 0.02], I2 = 45%, P = 0.15). Additionally, there were also no difference between the two groups in terms of length of hospital stay (mean difference (MD) -0.29, CI [-1.03, 0.46], I2 = 32%, P = 0.45) and length of ICU stay (MD -0.22, CI [-0.49 to 0.05], I2 = 72%, P = 0.10). CONCLUSIONS: This meta-analysis showed that exogenous NO administration via CBP had no benefits on the duration of mechanical ventilation, the length of postoperative hospital, and ICU stay after pediatric heart surgery.

Exendin-4, a glucagon-like peptide-1 receptor agonist, alleviates muscular dysfunction and wasting in a streptozotocin-induced diabetic mouse model compared to metformin.

Diabetic muscular atrophy is becoming a fast-growing problem worldwide, including sarcopenia, which is associated with substantial mortality and morbidity risk. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been marketed and suggested to exert protective effects on not only glycemic control but also diabetic complications in diabetic patients. In this study, we investigated the therapeutic use of GLP-1RAs exendin-4, compared to antidiabetic drug metformin, for the intervention of muscular dysfunction during diabetic conditions using a streptozotocin (STZ)-induced diabetic mouse model. The results showed that both exendin-4 and metformin could effectively alleviate hyperglycemia in diabetic mice, and also counteract diabetes-induced muscle weight loss, weaker grip, and changes in muscle fiber cross-sectional area distribution. Unexpectedly, exendin-4, but not metformin, enhanced the increased kidney weight and histological change in diabetic mice. Taken together, these findings suggest that both exendin-4 and metformin could effectively improve the diabetic hyperglycemia and muscular dysfunction; but exendin-4 may aggravate the nephropathy in STZ-induced diabetic mice.

Prenatal Parental Exposure to Metals and Birth Defects: A Prospective Birth Cohort Study.

While maternal exposure to high metal levels during pregnancy is an established risk factor for birth defects, the role of paternal exposure remains largely unknown. We aimed to assess the associations of prenatal paternal and maternal metal exposure and parental coexposure with birth defects in singletons. This study conducted within the Jiangsu Birth Cohort recruited couples in early pregnancy. We measured their urinary concentrations for 25 metals. A total of 1675 parent-offspring trios were included. The prevalence of any birth defects among infants by one year of age was 7.82%. Paternal-specific gravity-corrected urinary concentrations of titanium, vanadium, chromium, manganese, cobalt, nickel, copper, and selenium and maternal vanadium, chromium, nickel, copper, selenium, and antimony were associated with a 21-91% increased risk of birth defects after adjusting for covariates. These effects persisted after mutual adjustment for the spouse's exposure. Notably, when assessing the parental mixture effect by Bayesian kernel machine regression, paternal and maternal chromium exposure ranked the highest in relative importance. Parental coexposure to metal mixture showed a pronounced joint effect on the risk of overall birth defects, as well as for some specific subtypes. Our findings suggested a couple-based prevention strategy for metal exposure to reduce birth defects in offspring.

Scalable Fabrication of Large-Scale, 3D, and Stretchable Circuits.

Stretchable electronics have demonstrated excellent potential in wearable healthcare and conformal integration. Achieving the scalable fabrication of stretchable devices with high functional density is the cornerstone to enable the practical applications of stretchable electronics. Here, a comprehensive methodology for realizing large-scale, 3D, and stretchable circuits (3D-LSC) is reported. The soft copper-clad laminate (S-CCL) based on the "cast and cure" process facilitates patterning the planar interconnects with the scale beyond 1 m. With the ability to form through, buried and blind VIAs in the multilayer stack of S-CCLs, high functional density can be achieved by further creating vertical interconnects in stacked S-CCLs. The application of temporary bonding substrate effectively minimizes the misalignments caused by residual strain and thermal strain. 3D-LSC enables the batch production of stretchable skin patches based on five-layer stretchable circuits, which can serve as a miniaturized system for physiological signals monitoring with wireless power delivery. The fabrications of conformal antenna and stretchable light-emitting diode display further illustrate the potential of 3D-LSC in realizing large-scale stretchable devices.

Ultrasound-Mediated Lysozyme Microbubbles Targeting NOX4 Knockdown Alleviate Cisplatin-Exposed Cochlear Hair Cell Ototoxicity.

The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) protein plays an essential role in the cisplatin (CDDP)-induced generation of reactive oxygen species (ROS). In this study, we evaluated the suitability of ultrasound-mediated lysozyme microbubble (USMB) cavitation to enhance NOX4 siRNA transfection in vitro and ex vivo. Lysozyme-shelled microbubbles (LyzMBs) were constructed and designed for siNOX4 loading as siNOX4/LyzMBs. We investigated different siNOX4-based cell transfection approaches, including naked siNOX4, LyzMB-mixed siNOX4, and siNOX4-loaded LyzMBs, and compared their silencing effects in CDDP-treated HEI-OC1 cells and mouse organ of Corti explants. Transfection efficiencies were evaluated by quantifying the cellular uptake of cyanine 3 (Cy3) fluorescein-labeled siRNA. In vitro experiments showed that the high transfection efficacy (48.18%) of siNOX4 to HEI-OC1 cells mediated by US and siNOX4-loaded LyzMBs significantly inhibited CDDP-induced ROS generation to almost the basal level. The ex vivo CDDP-treated organ of Corti explants of mice showed an even more robust silencing effect of the NOX4 gene in the siNOX4/LyzMB groups treated with US sonication than without US sonication, with a marked abolition of CDDP-induced ROS generation and cytotoxicity. Loading of siNOX4 on LyzMBs can stabilize siNOX4 and prevent its degradation, thereby enhancing the transfection and silencing effects when combined with US sonication. This USMB-derived therapy modality for alleviating CDDP-induced ototoxicity may be suitable for future clinical applications.

Maternal Hypertensive Disorder in Pregnancy and Childhood Strabismus in Offspring.

Importance: Maternal hypertensive disorder in pregnancy (HDP) might affect ocular health in offspring; however, its association with strabismus remains unclear. Objective: To examine the association of maternal HDP with overall and type-specific strabismus in offspring. Design, Setting, and Participants: In the Jiangsu Birth Cohort study, a population-based study in China, pregnant women were recruited from April 24, 2014, to November 30, 2018. A total of 6195 offspring had maternal HDP diagnosis information, of whom 3078 were excluded due to having no information on ocular alignment or due to having ocular diseases other than strabismus or refractive error. Offspring underwent ocular examinations at 3 years of age, completed May 21, 2022. Data were analyzed from May 28, 2022, through December 15, 2023. Exposure: Maternal HDP, categorized into hypertension and preeclampsia or with blood pressure (BP) well controlled (systolic BP, <130; diastolic BP, <80 mm Hg) and poorly controlled (systolic BP, ≥130; diastolic BP, ≥80 mm Hg). Main Outcomes and Measures: The primary outcome was the incidence of strabismus in offspring. Poisson generalized linear mixed models were used to estimate the association between maternal HDP and strabismus. Results: Among the included 3117 children (mean [SD] age, 36.30 [0.74] months; 1629 boys [52.3%]), 143 (4.6%) were exposed to maternal HDP and 368 (11.8%) had strabismus. Offspring exposed to maternal HDP had an 82% increased risk of overall strabismus (relative risk [RR], 1.82 [95% CI, 1.21-2.74]), an 82% increased risk of exophoria (RR, 1.82 [95% CI, 1.11-3.00]), and a 136% increased risk of intermittent exotropia (RR, 2.36 [95% CI, 1.13-4.93]) compared with unexposed offspring. When considering the type of maternal HDP, the risk for all strabismus was high for offspring exposed to preeclampsia (RR, 2.38 [95% CI, 1.39-4.09]) compared with unexposed offspring. When considering the BP control level of maternal HDP, the risk for all strabismus was high for offspring born to mothers with HDP and poorly controlled BP (RR, 2.07 [95% CI, 1.32-3.24]) compared with unexposed offspring. Conclusions and Relevance: These findings suggest that maternal HDP is associated with an increased risk of offspring strabismus. Early screening of strabismus might be recommended for offspring with maternal HDP. Further exploration of the underlying mechanism of the association between HDP and strabismus is warranted.

Weak magnetic field promotes denitrification by stimulating ferromagnetic ion-containing metalloprotein expression.

Weak magnetic field (WMF) has been recognized to promote biological denitrification processes; however, the underlying mechanisms remain largely unexplored, hindering the optimization of its effectiveness. Here, we systematically investigated the effects of WMF on denitrification performance, enzyme activity, microbial community, and metaproteome in packed bed bioreactors treating high nitrate wastewater under different WMF intensities and C:N ratios. Results showed that WMFs significantly promoted denitrification by consistently stimulating the activities of denitrifying reductases and NAD+/NADH biosynthesis across decreasing C:N ratios. Reductases and electron transfer enzymes involved in denitrification were overproduced due to the significantly enriched overexpression of ferromagnetic ion-containing (FIC) metalloproteins. We also observed WMFs' intensity-dependent selective pressure on microbial community structures despite the effects being limited compared to those caused by changing C:N ratios. By coupling genome-centric metaproteomics and structure prediction, we found the dominant denitrifier, Halomonas, was outcompeted by Pseudomonas and Azoarcus under WMFs, likely due to its structural deficiencies in iron uptake, suggesting that advantageous ferromagnetic ion acquisition capacity was necessary to satisfy the substrate demand for FIC metalloprotein overproduction. This study advances our understanding of the biomagnetic effects in the context of complex communities and highlights WMF's potential for manipulating FIC protein-associated metabolism and fine-tuning community structure.

First-line serplulimab in metastatic colorectal cancer: Phase 2 results of a randomized, double-blind, phase 2/3 trial.

BACKGROUND: Whether or not the addition of immunotherapy to current standard-of-care treatments can improve efficacy in proficient mismatch repair (pMMR)/microsatellite-stable (MSS) metastatic colorectal cancer (mCRC), the predominant type of mCRC, is unclear. METHODS: This randomized, double-blind, phase 2 part of a phase 2/3 trial was conducted at 23 hospitals across China (ClinicalTrials.gov: NCT04547166). Patients with unresectable metastatic/recurrent colorectal adenocarcinoma and no prior systemic therapy were randomly assigned 1:1 to receive every-3-weeks intravenous serplulimab (300 mg) plus HLX04 (7.5 mg/kg) and XELOX (serplulimab group) or placebo (300 mg) plus bevacizumab (7.5 mg/kg) and XELOX (placebo group). The primary endpoint was independent radiology review committee (IRRC)-assessed progression-free survival (PFS). Secondary endpoints included other efficacy endpoints and safety. FINDINGS: Between July 16, 2021, and January 20, 2022, 114 patients were enrolled and randomly assigned to the serplulimab (n = 57) or placebo (n = 57) group. All patients had stage IV CRC, and 95.7% of the patients with available microsatellite instability (MSI) status were MSS. With a median follow-up duration of 17.7 months, median PFS was prolonged in the serplulimab group (17.2 vs. 10.7 months; hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.31-1.14). Although the median overall survival (OS) was not reached for either group, a trend of an OS benefit was observed for the serplulimab group (HR, 0.77; 95% CI, 0.41-1.45). 36 (65.5%) and 32 (56.1%) patients in the serplulimab and placebo groups had grade ≥3 treatment-related adverse events, respectively. CONCLUSIONS: Serplulimab plus HLX04 and XELOX exhibits promising efficacy and is safe and tolerable in patients with treatment-naive mCRC. FUNDING: This work was funded by Shanghai Henlius Biotech, Inc.

Inflammation due to ocular surface homeostasis imbalance caused by pterygia: tear lymphotoxin-alpha study and a literature review.

OBJECTIVE: To estimate the pterygium ocular surface state, and compare with healthy eyes and dry eyes. To investigate the inflammation due to pterygia growth by tear Lymphotoxin-alpha (LT α) test. DESIGN: Prospective, single-center study. PARTICIPANTS: 400 patients, divided into 100 pterygium group, 100 mild dry eye group, 100 moderate dry eye group, and 100 age-and sex-matched normal controls. METHODS: The non-invasive break-up time (NIBUT), tear meniscus height (TMH) test, corneal fluorescein staining (CFS), meibomian gland loss score (MGs), and lipid layer thickness (LLT) were evaluated in all patients. Pterygium status and ocular status in the pterygium group were collected. The tear LT α test was conducted in the pterygium patients group. RESULT: Pterygium can affect the ocular surface, leading to decreased tear film stability. The TMH, NIBUT, CFS, MGs, and lipid layer thickness can provide insights into this phenomenon. The presence of pterygium can change the structure and condition of the ocular surface. Tear LT α testing shows an abnormal decrease in LT α levels in pterygium patients. This indicates an immune-inflammation microenvironment that causes tissue repair deficiency. CONCLUSION: The dry eye triggered by the growth of pterygium may originate from the tear film instability due to pterygia. As an inflammatory index, LT α in the development of pterygium and the aggravation of dry eye patients can indicate that the ocular surface is in different inflammatory states. Future tear testing in LT α may be a potential indicator to assess the inflammatory status of the dry eye.