Enhanced sampling of protein conformational changes via true reaction coordinates from energy relaxation.

The bottleneck in enhanced sampling lies in finding collective variables that effectively accelerate protein conformational changes; true reaction coordinates that accurately predict the committor are the well-recognized optimal choice. However, identifying them requires unbiased natural reactive trajectories, which, paradoxically, require effective enhanced sampling. Using the generalized work functional method, we uncover that true reaction coordinates control both conformational changes and energy relaxation, enabling us to compute them from energy relaxation simulations.

The GRAS transcription factor OsGRAS2 negatively impacts salt tolerance in rice.

Transcription factor OsGRAS2 regulates salt stress tolerance and yield in rice. Plant-specific GRAS transcription factors are involved in many different aspects of plant growth and development, as well as in biotic and abiotic stress responses, although whether and how they participate in salt stress tolerance in rice (Oryza sativa) remains unclear. A screen of a previously generated set of activation-tagged lines revealed that Activation Tagging Line 63 (AC63) displayed a salt stress-sensitive phenotype.

Application of Protease-Hydrogen Peroxide Digestion Method in Forensic Diatom Examination.

Objectives: To propose a novel forensic diatom examination method, namely the protease-hydrogen peroxide (PHP) digestion method, and to explore its potential application in forensic practice.

Methods: The PHP digestion method was applied to process lung tissues and compared with the traditional nitric acid digestion method in terms of diatom quantity, recovery rate, proportion of diatom fragments, and recovery efficiency of different diatom genera.

Results: The PHP digestion method showed higher diatom quantity, recovery rate, and proportion of diatom fragments compared to the traditional nitric acid digestion method with statistical significance.

The novel mechanism on the inhibition of superoxide anion generating from xanthine oxidase in the presence of myricetin.

To gain an in-depth understanding of the process of myricetin (MY) inhibiting the generation of O from Xanthine Oxidase (XOD) at a novel perspective, the inhibiting pathway is necessary to be re-elaborated through inhibitory type, thermodynamic analysis and molecular simulation. The results demonstrated that MY is indeed a potent inhibiting agent for O producing from XOD, with the maximum value of 33.78 % in the inhibition of O.

A homozygous nonsense variant in HENMT1 causes male infertility in humans and mice.

Background: HENMT1 encodes a small RNA methyltransferase that plays a crucial role in mouse spermatogenesis through the methylation of the 3' end of PIWI-interacting RNAs.

Objectives: Our study aims to elucidate the relationship between HENMT1 and male infertility in humans.

Materials And Methods: A consanguineous family, having a single non-obstructive azoospermia patient was recruited for pathogenic variants screening.

Homozygous mutation causes oligoasthenoteratozoospermia in humans and mice.

Infertility represents a significant health concern, with sperm quantity and quality being crucial determinants of male fertility. Oligoasthenoteratozoospermia (OAT) is characterized by reduced sperm motility, lower sperm concentration, and morphological abnormalities in sperm heads and flagella. Although variants in several genes have been implicated in OAT, its genetic etiologies and pathogenetic mechanisms remain inadequately understood.

Predictive nomogram for 28-day mortality risk in mitral valve disorder patients in the intensive care unit: A comprehensive assessment from the MIMIC-III database.

Background: Mitral valve disorder (MVD) stands as the most prevalent valvular heart disease. Presently, a comprehensive clinical index to predict mortality in MVD remains elusive. The aim of our study is to construct and assess a nomogram for predicting the 28-day mortality risk of MVD patients.

OsGADD45a1: a multifaceted regulator of rice architecture, grain yield, and blast resistance.

The homolog gene of the Growth Arrest and DNA Damage-inducible 45 (GADD45) in rice functions in the regulation of plant architecture, grain yield, and blast resistance. The Growth Arrest and DNA Damage-inducible 45 (GADD45) family proteins, well-established stress sensors and tumor suppressors in mammals, serve as pivotal regulators of genotoxic stress responses and tumorigenesis. In contrast, the homolog and role of GADD45 in plants have remained unclear.

A Mitochondrial Localized Chaperone Regulator OsBAG6 Functions in Saline-Alkaline Stress Tolerance in Rice.

B-cell lymphoma 2 (Bcl-2)-associated athanogene (BAG) family genes play prominent roles in regulating plant growth, development, and stress response. Although the molecular mechanism underlying BAG's response to abiotic stress has been studied in Arabidopsis, the function of OsBAG underlying saline-alkaline stress tolerance in rice remains unclear. In this study, OsBAG6, a chaperone regulator localized to mitochondria, was identified as a novel negative regulator of saline-alkaline stress tolerance in rice.

Flexible Copper Nanowire/Polyvinylidene Fluoride Membranous Composites with a Frequency-Independent Negative Permittivity.

With the increasing popularity of wearable devices, flexible electronics with a negative permittivity property have been widely applied to wearable devices, sensors, and energy storage. In particular, a low-frequency dispersion negative permittivity in a wide frequency range can effectively contribute to the stable working performance of devices. In this work, polyvinylidene fluoride (PVDF) was selected as the flexible matrix, and copper nanowires (CuNWs) were used as the conductive functional filler to prepare a flexible CuNWs/PVDF composite film with a low-frequency dispersion negative permittivity.

Tubeimosides are pan-coronavirus and filovirus inhibitors that can block their fusion protein binding to Niemann-Pick C1.

SARS-CoV-2 and filovirus enter cells via the cell surface angiotensin-converting enzyme 2 (ACE2) or the late-endosome Niemann-Pick C1 (NPC1) as a receptor. Here, we screened 974 natural compounds and identified Tubeimosides I, II, and III as pan-coronavirus and filovirus entry inhibitors that target NPC1. Using in-silico, biochemical, and genomic approaches, we provide evidence that NPC1 also binds SARS-CoV-2 spike (S) protein on the receptor-binding domain (RBD), which is blocked by Tubeimosides.

Autophagy receptor OsNBR1 modulates salt stress tolerance in rice.

Autophagy receptor OsNBR1 modulates salt stress tolerance by affecting ROS accumulation in rice. The NBR1 (next to BRCA1 gene 1), as important selective receptors, whose functions have been reported in animals and plants. Although the function of NBR1 responses to abiotic stress has mostly been investigated in Arabidopsis thaliana, the role of NBR1 under salt stress conditions remains unclear in rice (Oryza sativa).

Plasma membrane-localized H-ATPase OsAHA3 functions in saline-alkaline stress tolerance in rice.

A novel function of plasma membrane-localized H-ATPase, OsAHA3, was identified in rice, which is involved in saline-alkaline tolerance and specifically responds to high pH during saline-alkaline stress. Saline-alkaline stress causes serious damage to crop production on irrigated land. Plants suffer more severe damage under saline-alkaline stress than under salinity stress alone.

Nutritional status associated with clinical outcomes in children with solid tumors: A retrospective cohort study from China.

Objective: To investigate the long-term changes in nutritional status in children with solid tumors during treatment and the relationship between nutritional status and clinical outcomes.

Methods: This study was a retrospective medical records review of data from children who were diagnosed with solid tumors and followed up for more than 3 months from January 2016 to December 2021 in China. Patient demographics and clinical information, including nutritional status, parenteral nutrition use, intensive care unit (ICU) transfers, infection during hospitalization, hospitalization frequency, length of stay, hospitalization costs and antibiotic costs, were collected to analyze the nutritional status of children with different types of solid tumors, the dynamic changes in nutritional status during treatment, and the relationship between nutritional status and clinical outcomes.

Development of a predictive nomogram for 28-day mortality risk in non-traumatic or post-traumatic subarachnoid hemorrhage patients.

Objective: Subarachnoid hemorrhage (SAH) is associated with high rates of mortality and permanent disability. At present, there are few definite clinical tools to predict prognosis in SAH patients. The current study aims to develop and assess a predictive nomogram model for estimating the 28-day mortality risk in both non-traumatic or post-traumatic SAH patients.

Type-B response regulator OsRR22 forms a transcriptional activation complex with OsSLR1 to modulate OsHKT2;1 expression in rice.

Soil salinity severely limits crop yields and quality. Plants have evolved several strategies to mitigate the adverse effects of salinity, including redistribution and compartmentalization of toxic ions using ion-specific transporters. However, the mechanisms underlying the regulation of these ion transporters have not been fully elucidated.

A novel NPHP4 homozygous missense variant identified in infertile brothers with multiple morphological abnormalities of the sperm flagella.

Purpose: Asthenozoospermia is an important cause of male infertility, and the most serious type is characterized by multiple morphological abnormalities of the sperm flagella (MMAF). However, the precise etiology of MMAF remains unknown. In the current study, we recruited a consanguineous Pakistani family with two infertile brothers suffering from primary infertility due to MMAF without obvious signs of PCD.

A recessive ACTL7A founder variant leads to male infertility due to acrosome detachment in Pakistani Pashtuns.

Male infertility affects more than 20 million men worldwide and is a major public health concern. Male infertility has a strong genetic basis, particularly for those unexplained cases. Here, through genetic analysis of three Pakistani families having eight infertile men with normal parameters in routine semen analysis, we identified a novel ACTL7A variant (c.

Loss-of-function mutations in CFAP57 cause multiple morphological abnormalities of the flagella in humans and mice.

Multiple morphological abnormalities of the sperm flagella (MMAF) are the most severe form of asthenozoospermia due to impaired axoneme structure in sperm flagella. Dynein arms are necessary components of the sperm flagellar axoneme. In this study, we recruited 3 unrelated consanguineous Pakistani families with multiple MMAF-affected individuals, who had no overt ciliary symptoms.

Cornichon protein CNIH4 is not essential for mice gametogenesis and fertility.

Background: Cornichon is a functionally conserved transmembrane protein family that generally acts as a cargo-sorting receptor and cycles between the ER and the Golgi. Four Cornichon family members (CNIH1-4) have been identified. The key residues responsible for CNIH1-3 to bind to AMPA receptors are not conserved in CNIH4.

Phosphorylation mutation impairs the promoting effect of spastin on neurite outgrowth without affecting its microtubule severing ability.

Spastin, a microtubule-severing enzyme, is known to be important for neurite outgrowth. However, the role of spastin post-translational modification, particularly its phosphorylation regulation in neuronal outgrowth, remains unclear. This study aimed to investigate the effects of eliminating spastin phosphorylation on the neurite outgrowth of rat hippocampal neurons.

Exact reaction coordinates for flap opening in HIV-1 protease.

The primary goal of protein science is to understand how proteins function, which requires understanding the functional dynamics responsible for transitions between different functional structures of a protein. A central concept is the exact reaction coordinates that can determine the value of committor for any protein configuration, which provide the optimal description of functional dynamics. Despite intensive efforts, identifying the exact reaction coordinates (RCs) in complex molecules remains a formidable challenge.

Plasma membrane-localized Hsp40/DNAJ chaperone protein facilitates OsSUVH7-OsBAG4-OsMYB106 transcriptional complex formation for OsHKT1;5 activation.

The salinization of irrigated land affects agricultural productivity. HIGH-AFFINITY POTASSIUM (K ) TRANSPORTER 1;5 (OsHKT1;5)-dependent sodium (Na ) transport is a key salt tolerance mechanism during rice growth and development. Using a previously generated high-throughput activation tagging-based T-DNA insertion mutant pool, we isolated a mutant exhibiting salt stress-sensitive phenotype, caused by a reduction in OsHKT1;5 transcripts.