TRIOL attenuates intracerebral hemorrhage injury by bidirectionally modulating microglia- and neuron-mediated hematoma clearance.

Intracerebral hemorrhage (ICH) represents the most severe subtype of stroke, and the lack of effective clinical pharmacotherapies poses a substantial threat to human health. Hematoma plays a crucial role in determining the prognosis of ICH patients by causing primary mechanical extrusion, followed by secondary brain injuries, such as cerebral edema, iron-mediated oxidative stress, and inflammation resulting from its degradation products. 5α-androst-3β,5α,6β-triol (TRIOL) is a neuroprotective steroid currently undergoing phase II clinical trial for acute ischemic stroke with anti-oxidative and anti-inflammatory properties.

Biallelic variants in the cause mitochondrial respiratory complex assembly defects associated with Leigh syndrome in probands.

Background: Variants in have been reported to be associated with Leigh syndrome. However, further expansion of the -phenotype and variants spectrum of -related Leigh syndrome are still required.

Methods: Two patients diagnosed with Leigh syndrome were recruited, and whole-exome sequencing was performed to identify the genetic variants responsible for the abnormal gait, dystonia, and bilateral basal ganglia lesions, followed by validation using Sanger sequencing.

Expanding the phenotypic and genetic spectrum of GTPBP3 deficiency: findings from nine Chinese pedigrees.

Background: GTPBP3 catalyzes τm(s) U biosynthesis at the 34th wobble position of mitochondrial tRNAs, the hypomodification of τmU leads to mitochondrial disease. While twenty-three variants of GTPBP3 have been reported worldwide, the genetic landscape in China remains uncertain.

Methods: By using whole-exome sequencing, the candidate individuals carrying GTPBP3 variants were screened and identified.

Ab-Amy 2.0: Predicting light chain amyloidogenic risk of therapeutic antibodies based on antibody language model.

Therapeutic antibodies have emerged as a promising treatment option for a wide range of diseases. However, the light chain of antibodies can potentially induce amyloidosis, a condition characterized by protein misfolding and aggregation, posing a significant safety concern. Therefore, it is crucial to assess the amyloidogenic risk of therapeutic antibodies during the early stages of drug development.

A novel m.5906G > a variant in MT-CO1 causes MELAS/Leigh overlap syndrome.

The MELAS/Leigh overlap syndrome manifests with a blend of clinical and radiographic traits from both MELAS and LS. However, the association of MELAS/Leigh overlap syndrome with MT-CO1 gene variants has not been previously reported. In this study, we report a patient diagnosed with MELAS/Leigh overlap syndrome harboring the m.

PhIP-Seq: methods, applications and challenges.

Phage-immunoprecipitation sequencing (PhIP-Seq) technology is an innovative, high-throughput antibody detection method. It enables comprehensive analysis of individual antibody profiles. This technology shows great potential, particularly in exploring disease mechanisms and immune responses.

Low methyl-esterified ginseng homogalacturonan pectins promote longevity of Caenorhabditis elegans via impairing insulin/IGF-1 signalling.

Panax ginseng C. A. Meyer (ginseng) is a medicinal plant widely used for promoting longevity.

Targeting G6PD to mitigate cartilage inflammation in TMJOA: The NOX4-ROS-MAPK axis as a therapeutic avenue.

Chondrocytes, known for their metabolic adaptability in response to varying stimuli, play a significant role in osteoarthritis (OA) progression. Glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, has recently been found to upregulate in OA chondrocyte. However, the exact role of G6PD in temporomandibular joint osteoarthritis (TMJOA) and its effect on chondrocyte function remains unclear.

Gallbladder dysfunction caused by MYPT1 ablation triggers cholestasis-induced hepatic fibrosis in mice.

Background: The incidence of gallbladder diseases is as high as 20%, but whether gallbladder diseases contribute to hepatic disorders remains unknown.

Methods: Here, we established an animal model of gallbladder dysfunction and assessed the role of a diseased gallbladder in cholestasis-induced hepatic fibrosis (CIHF).

Results: Mice with smooth muscle-specific deletion of Mypt1, the gene encoding the main regulatory subunit of myosin light chain phosphatase (myosin phosphatase target subunit 1 [MYPT1]), had apparent dysfunction of gallbladder motility.

MU variability in CBCT-guided online adaptive radiation therapy.

Purpose: CBCT-guided online-adaptive radiotherapy (oART) systems have been made possible by using artificial intelligence and automation to substantially reduce treatment planning time during on-couch adaptive sessions. Evaluating plans generated during an adaptive session presents significant challenges to the clinical team as the planning process gets compressed into a shorter window than offline planning. We identified MU variations up to 30% difference between the adaptive plan and the reference plan in several oART sessions that caused the clinical team to question the accuracy of the oART dose calculation.

Evaluating the necessity of lymph node sampling in lung adenocarcinoma with ground glass opacities.

Background: Ground glass opacity is observed frequently in the early stages of lung adenocarcinoma and is associated with a favorable prognosis and a low incidence of lymph node metastasis. However, the necessity of lymph node sampling in these patients is questionable, although current guidelines still recommend it.

Methods: Radiologic and clinical data were retrospectively collected and analyzed for 2,298 patients with lung cancer who underwent surgical resection for lesions ≤15 mm during 2022.

How Does the Number of Brain Metastases Correlate With Normal Brain Exposure in Single-Isocenter Multitarget Multifraction Stereotactic Radiosurgery.

Purpose: To investigate the relationship between normal brain exposure in LINAC-based single-isocenter multitarget multifraction stereotactic radiosurgery or stereotactic radiation therapy (SRT) and the number or volume of treated brain metastases, especially for high numbers of metastases.

Methods And Materials: A cohort of 44 SRT patients with 709 brain metastases was studied. Renormalizing to a uniform prescription of 27 Gy in 3 fractions, normal brain dose volume indices, including V23 Gy (volume receiving >23 Gy), V18 Gy (volume receiving >18 Gy), and mean dose, were evaluated on these plans against the number and the total volume of targets for each plan.

Machine Learning-Accelerated First-Principles Study of Atomic Configuration and Ionic Diffusion in LiGePS Solid Electrolyte.

The solid electrolyte LiGePS (LGPS) plays a crucial role in the development of all-solid-state batteries and has been widely studied both experimentally and theoretically. The properties of solid electrolytes, such as thermodynamic stability, conductivity, band gap, and more, are closely related to their ground-state structures. However, the presence of site-disordered co-occupancy of Ge/P and defective fractional occupancy of lithium ions results in an exceptionally large number of possible atomic configurations (structures).

DOTAD: A Database of Therapeutic Antibody Developability.

The development of therapeutic antibodies is an important aspect of new drug discovery pipelines. The assessment of an antibody's developability-its suitability for large-scale production and therapeutic use-is a particularly important step in this process. Given that experimental assays to assess antibody developability in large scale are expensive and time-consuming, computational methods have been a more efficient alternative.

The predictive value of computed tomography value on high-resolution images in differentiating invasive from indolent lung adenocarcinoma.

Background: Invasive adenocarcinoma (IA) has a worse prognosis and different clinical management strategies compared to indolent lung adenocarcinoma including adenocarcinoma in situ (AIS) and minimally IA (MIA). The purpose of this study was to evaluate the predictive value of computed tomography (CT) value in differentiating invasive from indolent lung adenocarcinoma.

Methods: The pathological diagnoses and imaging data of confirmed lung adenocarcinomas manifested as lung nodules with homogeneous internal density which were surgically resected between August 2021 and July 2022 were retrospectively analyzed.

Dosimetric evaluation of LINAC-based single-isocenter multi-target multi-fraction stereotactic radiosurgery with more than 20 targets: comparing MME, HyperArc, and RapidArc.

Background: To compare the dosimetric quality of three widely used techniques for LINAC-based single-isocenter multi-target multi-fraction stereotactic radiosurgery (fSRS) with more than 20 targets: dynamic conformal arc (DCA) in BrainLAB Multiple Metastases Elements (MME) module and volumetric modulated arc therapy (VMAT) using RapidArc (RA) and HyperArc (HA) in Varian Eclipse.

Methods: Ten patients who received single-isocenter fSRS with 20-37 targets were retrospectively replanned using MME, RA, and HA. Various dosimetric parameters, such as conformity index (CI), Paddick CI, gradient index (GI), normal brain dose exposures, maximum organ-at-risk (OAR) doses, and beam-on times were extracted and compared among the three techniques.

Synthetic steroid of 5α-Androst-3β,5α,6β-Triol alleviates acute lung injury via inhibiting inflammation and oxidative stress.

Acute lung injury (ALI) is a severe and potentially fatal respiratory condition with limited treatment options. The pathological evolution of ALI is driven by persistent inflammation, destruction of the pulmonary vascular barrier and oxidative stress. Evidence from prior investigations has identified 5α-androst-3β,5α,6β-Triol (TRIOL), a synthetic analogue of the naturally occurring neuroprotective compound cholestane-3β,5α,6β-triol, possesses notable anti-inflammatory and antioxidative properties.

Crohn's disease as the intestinal manifestation of pan-lymphatic dysfunction: An exploratory proposal based on basic and clinical data.

Crohn's disease (CD) is caused by immune, environmental, and genetic factors. It can involve the entire gastrointestinal tract, and although its prevalence is rapidly increasing its etiology remains unclear. Emerging biological and small-molecule drugs have advanced the treatment of CD; however, a considerable proportion of patients are non-responsive to all known drugs.

Immunogenicity Assessment of Therapeutic Peptides.

The application of therapeutic peptides in clinical practice has significantly progressed in the past decades. However, immunogenicity remains an inevitable and crucial issue in the development of therapeutic peptides. The prediction of antigenic peptides presented by MHC class II is a critical approach to evaluating the immunogenicity of therapeutic peptides.

Establishing and validation of the VBV score for assessing Lung ground-glass nodules based on high-resolution computed tomography.

Background: The widespread utilization of chest High-resolution Computed Tomography (HRCT) has prompted detection of pulmonary ground-glass nodules (GGNs) in otherwise asymptomatic individuals. We aimed to establish a simple clinical risk score model for assessing GGNs based on HRCT.

Methods: We retrospectively analyzed 574 GGNs in 574 patients undergoing HOOK-WIRE puncture and pulmonary nodule surgery from January 2014 to November 2018.

SAGESDA: Multi-GraphSAGE networks for predicting SnoRNA-disease associations.

Over the years, extensive research has highlighted the functional roles of small nucleolar RNAs in various biological processes associated with the development of complex human diseases. Therefore, understanding the existing relationships between different snoRNAs and diseases is crucial for advancing disease diagnosis and treatment. However, classical biological experiments for identifying snoRNA-disease associations are expensive and time-consuming.

Novel 6/7/6 ring system diterpenoids and cytochalasins from the fungus Eutypella scoparia GZU-4-19Y and their anti-inflammatory activity.

Two new compounds eutyditerpenoid A (1) and seco-phenochalasin B (5), together with seven known compounds diaporthein A (2), aspergillon A (3), phenochalasin B (4), cytochalasins Z and Z (6 and 7), scoparasins A and B (8 and 9) were isolated from marine-derived Eutypella scoparia GZU-4-19Y. Among them, eutyditerpenoid A (1) with a rare 6/7/6 ring system possesing an anhydride moiety was the first example in the pimarane-type diterpenoids. Their structures were determined based on spectroscopic methods and the electronic circular dichroism (ECD) calculations.

Neo-adjuvant chemotherapy plus immunotherapy in resectable N1/N2 NSCLC.

Background: Locally advanced non-small cell lung cancer (NSCLC) with N1/N2 lymph node metastasis is challenging with poor survival. Neo-adjuvant chemo-immunotherapy has gained benefits in a proportion of these patients. However no specific biomarker has been proved to predict the effect before therapy.

Development of a Set of Wheat-Rye Derivative Lines from Hexaploid Triticale with Complex Chromosomal Rearrangements to Improve Disease Resistance, Agronomic and Quality Traits of Wheat.

An elite hexaploid triticale Yukuri from Australia was used as a bridge for transferring valuable genes from L. into common wheat for enriching the genetic variability of cultivated wheat. Non-denaturing-fluorescence in situ hybridization (ND-FISH) identified that Yukuri was a secondary triticale with a complete set of rye chromosomes and a 6D(6A) substitution.