Neoadjuvant chemoradiation with or without PD-1 blockade in locally advanced rectal cancer: a randomized phase 2 trial.

Radiotherapy displays unique antitumor synergism with immune checkpoint inhibitors, which is indicated by high pathological complete response (pCR) rates from single-arm trials of locally advanced rectal cancer (LARC). Here we test the efficacy and safety of the radiation-immune checkpoint inhibitor combination in patients with LARC in a phase 2, randomized trial conducted in eight major colorectal cancer centers in Beijing. In total, 186 eligible all-comer (proficient mismatch repair and deficient mismatch repair) participants were enrolled.

The galactokinase enzyme of yeast senses metabolic flux to stabilize galactose pathway regulation.

Nutrient sensors allow cells to adapt their metabolisms to match nutrient availability by regulating metabolic pathway expression. Many such sensors are cytosolic receptors that measure intracellular nutrient concentrations. One might expect that inducing the metabolic pathway that degrades a nutrient would reduce intracellular nutrient levels, destabilizing induction.

Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity.

Identifying cell types and brain regions critical for psychiatric disorders and brain traits is essential for targeted neurobiological research. By integrating genomic insights from genome-wide association studies with a comprehensive single-cell transcriptomic atlas of the adult human brain, we prioritized specific neuronal clusters significantly enriched for the SNP-heritabilities for schizophrenia, bipolar disorder, and major depressive disorder along with intelligence, education, and neuroticism. Extrapolation of cell-type results to brain regions reveals the whole-brain impact of schizophrenia genetic risk, with subregions in the hippocampus and amygdala exhibiting the most significant enrichment of SNP-heritability.

The challenges of quantifying the effects of housing on health using observational data.

Housing is an often overlooked yet fundamental social determinant of health. Like other social epidemiology exposures, housing faces a tension between the promise of modern causal inference methods and the messy reality of complex social processes and reliance on observational data. We use examples from over a decade of research to illustrate some of the key challenges in undertaking causally focused healthy housing research and demonstrate approaches that have been applied to address these challenges.

Impact of regenerative procedure on the healing process following surgical root canal treatment: A systematic review and meta-analysis.

Introduction: Different Guided Tissue Regeneration (GTR) procedures, such as membranes, bone substitute materials, and Autologous Platelet Concentrates (APCs), have been applied after surgical root canal treatment (SRCT), which produce different outcomes. This study aimed to evaluate the impact of regenerative procedures on the healing process following SRCT.

Methods: A comprehensive search of PubMed, Embase, Scopus, Cochrane, and the Web of Science found Randomized Controlled Trials (RCTs) published until February 25, 2024.

Quantitative site-specific N-glycosylation analysis reveals IgG glyco-signatures for pancreatic cancer diagnosis.

Background: Pancreatic cancer is a highly aggressive tumor with a poor prognosis due to a low early detection rate and a lack of biomarkers. Most of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). Alterations in the N-glycosylation of plasma immunoglobulin G (IgG) have been shown to be closely associated with the onset and development of several cancers and could be used as biomarkers for diagnosis.

Deciphering the code of temperature rise on aerobic granular sludge stability: A DSF-c-di-GMP mediated regulatory mechanism.

Diffusible signal factor (DSF)-c-di-GMP-mediated strategies have been proposed as an effective regulatory approach for signal molecules in aerobic granular sludge (AGS). The increase in temperature from low to normal levels had a significant impact on AGS stability. In this study, two reactors were established to investigate the effects of different temperature rise modes (abrupt or gradual) on AGS stability.

A novel proceduralized donor liver back-table preparation technique minimizes hemorrhage following liver implantation in orthotropic liver transplantation.

Background: Intraoperative hemorrhage is one of the major complications of orthotopic liver transplantation (OLT) and is mainly caused by technical difficulties of the surgical procedure besides primary liver diseases. The present study aimed to evaluate the feasibility and clinical effects of a novel proceduralized donor liver back-table preparation (DLBTP) technique for use in OLT.

Methods: This retrospective study was conducted between January 2018 and June 2020 based on patients who had undergone OLT.

Methane emissions from the riverine sandy wetlands on the Mongolia Plateau.

Methane (CH) processes and fluxes have been widely investigated in low-latitude tropical wetlands and high-latitude boreal peatlands. In the mid-latitude Mongolia Plateau, however, CH processes and fluxes have been less studied, particularly in riverine wetlands. In this study, in situ experiments were conducted in the riverine sandy wetlands of the Mongolia Plateau to gain a better understanding of CH emissions and their influencing mechanisms.

A Microtubule-Associated Protein Functions in Preventing Oocytes from Evading the Spindle Assembly Checkpoint.

Aneuploidy eggs are a common cause of human infertility, spontaneous abortion, or trisomy syndromes. The spindle assembly checkpoint (SAC) plays a crucial role in preventing aneuploidy in oocytes, yet it is unclear if additional mechanisms exist to ensure oocyte adherence to this checkpoint. It is now revealed that the microtubule-associated protein NUSAP can prevent oocytes from evading the SAC and regulate the speed of the cell cycle.

The metabolomics provides insights into the Pacific abalone () response to low temperature stress.

The low temperatures in winter, particularly the cold spells in recent years, have posed significant threats to China's abalone aquaculture industry. The low temperature tolerance of cultured abalone has drawn plenty of attention, but the metabolic response of abalone to low-temperature stress remains unclear. In this study, we investigated the metabolomic analysis of Pacific abalone () during low-temperature stress.

High-Sensitivity, High-Resolution Miniaturized Spectrometers for Ultraviolet to Near-Infrared Using Guided-Mode Resonance Filters.

Miniaturized spectrometers have significantly advanced real-time analytical capabilities in fields such as environmental monitoring, healthcare diagnostics, and industrial quality control by enabling precise on-site spectral analysis. However, achieving high sensitivity and spectral resolution within compact devices remains a significant challenge, particularly when detecting low-concentration analytes or subtle spectral variations critical for chemical and molecular analysis. This study introduces an innovative approach employing guided-mode resonance filters (GMRFs) to address these limitations.

Evaluation of Sustained Intraocular Pressure Elevations Across Antivascular Endothelial Growth Factor Agents.

To evaluate the effect of antivascular endothelial growth factor (anti-VEGF) agents on the development of sustained intraocular pressure (IOP) elevations. This single-center retrospective cohort study included eyes receiving anti-VEGF injections for various indications along with nontreated fellow eyes from 2012 to 2022. Patients were grouped according to treatment with bevacizumab, ranibizumab, or aflibercept.

ALDH3A1-mediated detoxification of reactive aldehydes contributes to distinct muscle responses to denervation and Amyotrophic Lateral Sclerosis progression.

Different muscles exhibit varied susceptibility to degeneration in Amyotrophic Lateral Sclerosis (ALS), a fatal neuromuscular disorder. Extraocular muscles (EOMs) are particularly resistant to ALS progression and exploring the underlying molecular nature may deliver great therapeutic value. Reactive aldehyde 4-hydroxynonenal (HNE) is implicated in ALS pathogenesis and ALDH3A1 is an inactivation-resistant intracellular detoxifier of 4-HNE protecting eyes against UV-induced oxidative stress.

Kiwifruit spatiotemporal multiomics networks uncover key tissue-specific regulatory processes throughout the life cycle.

Kiwifruit (Actinidia chinensis), a recently commercialized horticultural crop, is rich in various nutrient compounds. However, the regulatory networks controlling the dynamic changes in key metabolites among different tissues remain largely unknown. Here, high-resolution spatiotemporal datasets obtained by ultraperformance liquid chromatography-tandem mass spectrometry methodology and RNA-seq were employed to investigate the dynamic changes in the metabolic and transcriptional landscape of major kiwifruit tissues across different developmental stages, including from fruit skin, outer pericarp, inner pericarp, and fruit core.

Transplant-associated TMA: the conundrum of diagnosis and treatment.

Transplant-associated thrombotic microangiopathy (TA-TMA) after hematopoietic cell transplantation is characterized by microangiopathic hemolytic anemia (MAHA) with persistent schistocytosis, elevated markers of hemolysis, thrombocytopenia, and microvascular thrombosis leading to ischemic injuries in the kidneys and other organs. The initial evaluation of the disease requires confirmation of non-immune MAHA and careful examination of known secondary causes of TMA. Due to increased likelihood of long-term renal failure and overall mortality, a rapid diagnosis and treatment of the underlying trigger is needed.

Hapalindole Q suppresses autophagosome-lysosome fusion by promoting YAP1 degradation via chaperon-mediated autophagy.

Autophagy is a conserved catabolic process crucial for maintaining cellular homeostasis and has emerged as a promising therapeutic target for many diseases. Mechanistically novel small-molecule autophagy regulators are highly desirable from a pharmacological point of view. Here, we report the macroautophagy-inhibitory effect of hapalindole Q, a member of the structurally intriguing but biologically understudied hapalindole family of indole terpenoids.

The stability of CsGeX (X = I, Br, Cl) selectively tuned by the crystal structures and halide ions as inferred from the calculated phonon spectrum.

In spite of the considerable advancements achieved in enhancing the power conversion efficiency (PCE) of lead-based all-inorganic perovskite solar cells, there persists a need for materials that are both more stable and environmentally friendly. This investigation systematically explores the structural and thermodynamic stability, and electronic properties of Ge-based all-inorganic perovskite CsGeX (X = Cl, Br, I) in two space groups, 3̄ and 3, utilizing first-principles calculations. Introducing the novel concept of the "imaginary frequency coefficient" alongside the tolerance factor and stabilizing the chemical potential window, we collectively characterize the stability of CsGeX based on the phonon spectrum and phonon density of states calculations.

Buckled-layer KMnO: a novel cathode for potassium-ion batteries.

A novel buckled-layer KMnO cathode was synthesized, featuring P2-oxygen stacking and P3-K sites. The presence of two independent manganese sites significantly influences the charge distribution and diffusion pathways of potassium ions during the charge and discharge processes, resulting in exceptional electrochemical performance. A reversible capacity of 105 mA h g at 100 mA g and remarkable rate capability of 70 mA h g at 1 A g were achieved, surpassing those of most previously reported layered transition metal oxide cathodes.

Tissue accumulation and hepatotoxicity of 8:2 chlorinated polyfluoroalkyl ether sulfonate: A multi-omics analysis deciphering hepatic amino acid metabolic dysregulation in mice.

8:2 Chlorinated polyfluoroalkyl ether sulfonate (8:2 Cl-PFESA) is a substitute for perfluorooctane sulfonate and an emerging environmental pollutant, yet its bioaccumulation and health risks are poorly understood. We established a subchronic exposure model in mice (0.04, 0.