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Crystalline solids with extended non-interpenetrating three-dimensional crystal structures were synthesized that support well-defined pores with internal diameters of up to 48 angstroms. The Zn 4 O(CO₂) 6 unit was joined with either one or two kinds of organic link, 4,4', 4\"-[benzene-l, 3,5-triyl-tris (ethyne-2, l-diyl)] tribenzoate (BTE), 4'4',4\"-[benzene-1,3,5-triyl-tris(benzene-4,1-diyl)] tribenzoate (BBC), 4,4',44\"-benzene-1,3,5-triyl-tribenzoate (BTB)/2,6-naphthalenedicarboxylate (NDC), and BTE/biphenyl-4,4'-dicarboxylate (BPDC), to give four metal-organic frameworks (MOFs), MOF-180, -200, -205, and -210, respectively. Members of this series of MOFs show exceptional porosities and gas (hydrogen, methane, and carbon dioxide) uptake capacities. For example, MOF-210 has Brunauer-Emmett-Teller and Langmuir surface areas of 6240 and 10,400 square meters per gram, respectively, and a total carbon dioxide storage capacity of 2870 milligrams per gram. The volume-specific internal surface area of MOF-210 (2060 square meters per cubic centimeter) is equivalent to the outer surface of nanoparticles (3-nanometer cubes) and near the ultimate adsorption limit for solid materials.

The second to fourth digit ratio （2D：4D） has been proposed as a putative biomarker for prenatal testosterone and covaries with the sensitivity of the androgen receptor （AR）. Both prenatal testosterone and the AR play a central role in penile growth. In this study, we investigated the relationship between digit ratio and penile length. Korean men who were hospitalized for urological surgery at a single tertiary academic centre were examined in this study, and 144 men aged 20 years or older who gave informed consent were prospectively enrolled. Right-hand second- and fourth-digit lengths were measured by a single investigator prior to measurement of penile length. Under anaesthesia, flaccid and stretched penile lengths were measured by another investigator who did not measure nor have any the information regarding the digit lengths. Univariate and multivariate analysis using linear regression models showed that only height was a significant predictive factor for flaccid penile length （univariate analysis： r=0. 185, P=-0.026; multivariate analysis： r=-0.172, P=0.038） and that only digit ratio was a significant predictive factor for stretched penile length （univariate analysis： r=-0.216, P=0.009; multivariate analysis： r=-0.201, P=0.024; stretched penile length=-9.201 xdigit ratio ＋ 20.577）. Based on this evidence, we suggest that the digit ratio can predict adult penile size and that the effects of prenatal testosterone may in part explain the differences in adult penile length.

Cytoplasmic chloroplast (cp) genomes and nuclear ribosomal DNA (nR) are the primary sequences used to understand plant diversity and evolution. We introduce a high-throughput method to simultaneously obtain complete cp and nR sequences using Illumina platform whole-genome sequence. We applied the method to 30 rice specimens belonging to nine Oryza species. Concurrent phylogenomic analysis using cp and nR of several of specimens of the same Oryza AA genome species provides insight into the evolution and domestication of cultivated rice, clarifying three ambiguous but important issues in the evolution of wild Oryza species. First, cp-based trees clearly classify each lineage but can be biased by inter-subspecies cross-hybridization events during speciation. Second, O. glumaepatula , a South American wild rice, includes two cytoplasm types, one of which is derived from a recent interspecies hybridization with O. longistminata . Third, the Australian O. rufipogan -type rice is a perennial form of O. meridionalis .

Since its initial description 35 years ago as an inducible molecule expressed in cytotoxic and helper T cells, 4-1BB has emerged as a crucial receptor in T-cell-mediated immune functions. Numerous studies have demonstrated the involvement of 4-1BB in infection and tumor immunity. However, the clinical development of 4-1BB agonist antibodies has been impeded by the occurrence of strong adverse events, notably hepatotoxicity, even though these antibodies have exhibited tremendous promise in in vivo tumor models. Efforts are currently underway to develop a new generation of agonist antibodies and recombinant proteins with modified effector functions that can harness the potent T-cell modulation properties of 4-1BB while mitigating adverse effects. In this review, we briefly examine the role of 4-1BB in T-cell biology, explore its clinical applications, and discuss future prospects in the field of 4-1BB agonist immunotherapy. Focus on 4-1BB immunotherapy 4-1BB is a costimulatory T-cell receptor expressed on activated T cells and natural killer cells. Targeting 4-1BB with agonistic antibodies is a promising immuno-oncology approach and has shown potential in preclinical animal models. However, the clinical use of agonistic 4-1BB antibodies for cancer immunotherapy has been hampered by adverse effects and insufficient anti-cancer activity. In this review, the authors provide an overview of the 4-1BB costimulatory pathways in T-cell-mediated cancer immunity and summarize ongoing efforts to develop improved therapies through 4-1BB stimulation. They also explore potential solutions to address the challenges encountered in clinical trials. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

Doil Choi and colleagues report the genome sequence of the hot pepper, Capsicum annuum , as well as the resequencing of two cultivated peppers and a wild species, Capsicum chinense . Comparative genomic analysis across Solanaceae provides insights into genome expansion, pungency, ripening and disease resistance in hot peppers. Hot pepper ( Capsicum annuum ), one of the oldest domesticated crops in the Americas, is the most widely grown spice crop in the world. We report whole-genome sequencing and assembly of the hot pepper (Mexican landrace of Capsicum annuum cv. CM334) at 186.6× coverage. We also report resequencing of two cultivated peppers and de novo sequencing of the wild species Capsicum chinense . The genome size of the hot pepper was approximately fourfold larger than that of its close relative tomato, and the genome showed an accumulation of Gypsy and Caulimoviridae family elements. Integrative genomic and transcriptomic analyses suggested that change in gene expression and neofunctionalization of capsaicin synthase have shaped capsaicinoid biosynthesis. We found differential molecular patterns of ripening regulators and ethylene synthesis in hot pepper and tomato. The reference genome will serve as a platform for improving the nutritional and medicinal values of Capsicum species.

The balance between major DNA double-strand break (DSB) repair pathways is influenced by binding of the Ku complex, a XRCC5/6 heterodimer, to DSB ends, initiating non-homologous end joining (NHEJ) but preventing additional DSB end resection and homologous recombination (HR). However, the key molecular cue for Ku recruitment to DSB sites is unknown. Here, we report that FOXL2, a forkhead family transcriptional factor, directs DSB repair pathway choice by acetylation-dependent binding to Ku. Upon DSB induction, SIRT1 translocates to the nucleus and deacetylates FOXL2 at lysine 124, leading to liberation of XRCC5 and XRCC6 from FOXL2 and formation of the Ku complex. FOXL2 ablation enhances Ku recruitment to DSB sites, imbalances DSB repair kinetics by accelerating NHEJ and inhibiting HR, and thus leads to catastrophic genomic events. Our study unveils the SIRT1-(de)acetylated FOXL2-Ku axis that governs the balance of DSB repair pathways to maintain genome integrity. The Ku complex, formed by XRCC5/6 heterodimer, binds to double strand break (DSB) ends, initiating non homologous end joining (NHEJ) and preventing homologous recombination (HR). Here, the authors reveal that FOXL2, a forkhead family transcriptional factor, directs DSB repair pathway choice by acetylation-dependent binding to Ku.

Senna tora is a widely used medicinal plant. Its health benefits have been attributed to the large quantity of anthraquinones, but how they are made in plants remains a mystery. To identify the genes responsible for plant anthraquinone biosynthesis, we reveal the genome sequence of S. tora at the chromosome level with 526 Mb (96%) assembled into 13 chromosomes. Comparison among related plant species shows that a chalcone synthase-like (CHS-L) gene family has lineage-specifically and rapidly expanded in S. tora . Combining genomics, transcriptomics, metabolomics, and biochemistry, we identify a CHS-L gene contributing to the biosynthesis of anthraquinones. The S. tora reference genome will accelerate the discovery of biologically active anthraquinone biosynthesis pathways in medicinal plants. Anthraquinones are aromatic polyketides and have been used for treating various diseases, but the biosynthetic pathway is unclear. Here, the authors assemble the genome of an anthraquinone-producing medicinal plant Senna tora and show the evidences that CHS-like genes may be involved in anthraquinone biosynthesis.

Unlike graphene, the existence of bandgaps (1–2 eV) in the layered semiconductor molybdenum disulphide, combined with mobility enhancement by dielectric engineering, offers an attractive possibility of using single-layer molybdenum disulphide field-effect transistors in low-power switching devices. However, the complicated process of fabricating single-layer molybdenum disulphide with an additional high- k dielectric layer may significantly limit its compatibility with commercial fabrication. Here we show the first comprehensive investigation of process-friendly multilayer molybdenum disulphide field-effect transistors to demonstrate a compelling case for their applications in thin-film transistors. Our multilayer molybdenum disulphide field-effect transistors exhibited high mobilities (>100 cm 2  V −1  s −1 ), near-ideal subthreshold swings (~70 mV per decade) and robust current saturation over a large voltage window. With simulations based on Shockley's long-channel transistor model and calculations of scattering mechanisms, these results provide potentially important implications in the fabrication of high-resolution large-area displays and further scientific investigation of various physical properties expected in other layered semiconductors. Molybdenum disulphide offers some tantalizing advantages over graphene as a material with which to fabricate field-effect transistors. Kim et al . present a comprehensive study of field-effect transistors made from multilayer samples of MoS 2 and find that they can achieve high carrier mobilities.

Abstract BACKGROUND Early brain injury (EBI) after subarachnoid hemorrhage (SAH) is an important determinant of clinical outcomes. However, a major hindrance to studies of EBI is the lack of radiographic surrogate marker. OBJECTIVE To propose a scoring system based on early changes in clinically obtained computed tomography (CT), called the Subarachnoid hemorrhage Early Brain Edema Score (SEBES). METHODS Patients with spontaneous aneurysmal SAH and a CT within 24 h of ictus were included. We defined SEBES as a scale of 0 to 4 points according to the (1) absence of visible sulci caused by effacement of sulci or (2) absence of visible sulci with disruption of the gray–white matter junction at 2 predetermined levels in each hemisphere. Prognostic value of the SEBES grade for the prediction of delayed cerebral ischemia (DCI) and unfavorable outcomes was assessed. A separate cohort of patients was used as a validation cohort. RESULTS Of the 164 subjects in our study, high-grade SEBES (3 or 4 points) was identified in 48 patients (29.3%). CT interobserver reliability of SEBES grades was high with a Kappa value of 0.89. After adjusting for covariables, SEBES was identified as an independent predictor of DCI (OR = 2.24, 95% CI: 1.58–3.17) and unfavorable outcome (OR = 3.45, 95% CI: 1.95–6.07). In our validation cohort, 84 subjects showed similar predictive power of SEBES for a prediction of DCI and unfavorable long-term outcome. CONCLUSION SEBES may be a surrogate marker of EBI and predicts DCI and clinical outcomes after SAH.

This multicentre, prospective, single-arm study evaluated safinamide as add-on therapy to levodopa in Korean patients with Parkinson’s disease (PD) with motor fluctuations with ≥ 1.5 h of “off” time daily, who took levodopa ≥ 3 times/day ( n  = 199). Baseline levodopa and dopamine agonist doses were maintained without escalation during the 18-week treatment period. Participants received safinamide 50 mg/day for 2 weeks and 100 mg/day thereafter. PD diaries and questionnaires (Parkinson’s Disease Questionnaire, PDQ-39; Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale, MDS–UPDRS part 3 and part 4; King’s Parkinson’s Disease Pain Scale, KPPS; Mini-Mental State Examination, MMSE) were assessed at baseline and at week 18. Treatment-emergent adverse events (TEAEs) were recorded. Mean disease duration was 6.6 years, and mean levodopa equivalent daily dose was 721.1 mg/day. At week 18, significant improvements from baseline were seen for the co-primary endpoints, mean daily “off” time (− 1.3 ± 2.4 h, p  < 0.001) and quality of life (QoL) based on PDQ-39 summary index (− 2.7 ± 10.3, p  < 0.001), Moreover, significant improvements were seen in motor symptoms and motor complications (MDS-UPDRS part 3 and 4), daily “on” time without dyskinesia (all p  < 0.001) and pain (KPPS; p  = 0.013). TEAEs occurred in 40.2% of patients, with most being mild in severity. In conclusion, safinamide at a dosage of 100 mg/day significantly improved motor symptoms, QoL, and pain, and demonstrated a favourable safety profile without levodopa dosage escalation during the 18-week treatment period in Korean patients with PD. Trial registration number and date : NCT05312632, First Posted: April 5, 2022