Huperziacrassifolia (Lycopodiaceae), a new species from China based on morphological characters and molecular evidence.

A new species of the firmoss from China, Huperziacrassifolia sp. nov., is described and illustrated based on morphological characters and molecular evidence. The new species resembles species associated with the H.javanica complex, in particular H.javanica based on leaf shape and serrations, but can be easily distinguished by elliptic lanceolate and thick coriaceous leaves, well differentiated seasonal constriction zones, and reflexed leaf margins when get dried. Phylogenomic reconstruction using whole chloroplast genome sequences recovered H.crassifolia as sister to H.sutchueniana and only distantly related to morphological similar species H.javanica, H.nanlingensis, and H.serrata. The genome size 2C = 17.2 pg indicated the new species to be a tetraploid, whereas diploid H.javanica had a genome size of 8.7 pg. Morphological characters, distribution, and conservation status of the new species are also presented.

[Retracted] Brain cell apoptosis inhibition by butylphthalide in Alzheimer's disease model in rats.

[This retracts the article DOI: 10.3892/etm.2017.4322.].

Inflammatory signature-based theranostics for acute lung injury in acute type A aortic dissection.

Acute lung injury (ALI) is a serious adverse event in the management of acute type A aortic dissection (ATAAD). Using a large-scale cohort, we applied artificial intelligence-driven approach to stratify patients with different outcomes and treatment responses. A total of 2,499 patients from China 5A study database (2016-2022) from 10 cardiovascular centers were divided into 70% for derivation cohort and 30% for validation cohort, in which extreme gradient boosting algorithm was used to develop ALI risk model. Logistic regression was used to assess the risk under anti-inflammatory strategies in different risk probability. Eight top features of importance (leukocyte, platelet, hemoglobin, base excess, age, creatinine, glucose, and left ventricular end-diastolic dimension) were used to develop and validate an ALI risk model, with adequate discrimination ability regarding area under the receiver operating characteristic curve of 0.844 and 0.799 in the derivation and validation cohort, respectively. By the individualized treatment effect prediction, ulinastatin use was significantly associated with significantly lower risk of developing ALI (odds ratio [OR] 0.623 [95% CI 0.456, 0.851]; P = 0.003) in patients with a predicted ALI risk of 32.5-73.0%, rather than in pooled patients with a risk of <32.5 and >73.0% (OR 0.929 [0.682, 1.267], P = 0.642) (Pinteraction = 0.075). An artificial intelligence-driven risk stratification of ALI following ATAAD surgery were developed and validated, and subgroup analysis showed the heterogeneity of anti-inflammatory pharmacotherapy, which suggested individualized anti-inflammatory strategies in different risk probability of ALI.

Optimizing operation strategy to improve storage of intracellular carbon sources in anaerobic/oxic/anoxic system: Enhanced nitrogen removal by endogenous denitrification.

Endogenous denitrification (ED) can make full use of the carbon sources and avoid replenishment of it. However, strengthening the storage of intracellular carbon sources is an important factor in improving ED efficiency. In this study, employed batch experiments using real domestic wastewater in the anaerobic/oxic (A/O) process. The anaerobic and oxic processes were run for 4 h under ambient conditions with the dissolved oxygen (DO) concentrations in the oxic stage controlled at 0.5, 1.0, 1.5, and 3.0 mg/L, respectively. The results showed that the content of poly-ß-hydroxyalkanoates (PHA) reached its peak at 60 min (1.25 mmolC/L). And with DO concentrations of 1.5 mg/L, the contents of glycogen (Gly) were 27.74 mmolC/L. Subsequently, the AOA-SBR was established to investigate its effect on the long-term nitrogen removal performance of domestic wastewater by optimizing the anaerobic time and DO concentrations. The results showed that at an anaerobic time of 60 min and DO concentration of 1.5 mg/L, the storage of the intracellular carbon sources was highest and the total nitrogen (TN) removal efficiency increased to 82.12%. In addition, Candidatus Competibacter dominated gradually in the system as the strategy was optimized.

Anti-tumor effects of nanosecond pulsed electric fields in a murine model of pancreatic cancer.

Nanosecond Pulsed Electric Fields (nsPEFs) treatment has demonstrated anti-tumor effects on various cancer cell lines. However, the use of this treatment in pancreatic cancer is limited. This study demonstrated that nsPEFs treatment effectively suppressed the proliferation and metastasis of pancreatic cancer cells, while also inducing DNA damage. Meanwhile, animal experiments have shown that nsPEFs effectively suppressed the growth of pancreatic cancer, even in cases where the tumor volume exceeded 500-600 mm3 at the initiation of treatment. Notably, a single treatment session was found to significantly inhibit tumor growth, while also showing no adverse effects on the main organs of the mice. RNA sequencing and bioinformatics revealed that seven key genes (CDK1, CENPA, UBE2C, CCNB2, PLK1, CCNA2, and CCNB14) were significantly correlated with the overall survival rate of patients with pancreatic cancer. Through the application of the competing endogenous RNA (ceRNA) hypothesis, two miRNAs (has-let-7b-5p and hsa-miR-193b-3p) and four lncRNAs (MIR4435-2HG, ZNF436-AS1, LINC01089, and MIR4435-2HG) were identified as significantly impacting the overall survival of pancreatic cancer patients. We have effectively developed an mRNA-miRNA-lncRNA network that has the potential to stimulate further investigation into the underlying mechanisms of nsPEFs on pancreatic cancer.

Toxicity of antimony to plants: Effects on metabolism of N and S in a rice plant.

Excess antimony (Sb) has been shown to damage plant growth. Rice plants readily absorb a large amount of Sb after a long period of flooding, yet the mechanisms underlying Sb toxicity in plants have not been solved. This study was conducted to explore the effects of Sb on the uptake of N and S, and monitor the concentrations of reduced glutathione (GSH) and enzymes associated with these processes. In addition, we analyzed differentially expressed metabolites (DEMs) correlated with amino acids (AAs) and oligopeptides, specifically DEMs containing sulfur (S), GSH and indole-3-acetic acid (IAA). The results showed that antimonite [Sb(III)] inhibited shoot growth whereas antimonate [Sb(V)] stimulated shoot growth. Interestingly, Sb(III)5/10 enhanced shoot concentrations of total nitrogen (N), NH4+-N [only at Sb(III)10] and S; but reduced the shoot concentrations of NO3-N and soluble protein. Sb(III)5/10 addition significantly increased oxidized glutathione (GSSG) concentration and activities of glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST) but non-significantly affected concentration of reduced glutathione (GSH) and activities of γ-glutamylcysteine synthetase (GCL) and glutathione reductase (GR), suggesting Sb(III) restricted GSH recycling. Addition of Sb (1) increased the abundance of DEMs associated with lignins, Ca uptake, toxicity/detoxification, and branched chain AAs; (2) decreased the abundance of AAs inclcuding isoleucine (Ile), leucine (Leu), tryptophan (Trp), tyrosine (Tyr) and histidine (His); (3) increased the abundance of arginine (Arg), putrescine (Put) and spermidine (Spd); and (4) affected methylation and acetylation of many AAs, especially acetylation.

A Case of Adult Hereditary Spherocytosis Concomitant with Gilbert Syndrome Caused by Mutations in SPTB and UGT1A1.

Hereditary spherocytosis (HS) is the most common hereditary hemolytic disease with defects in red blood cells (RBC) membrane proteins caused by mutations in membrane protein genes, like SPTB, SPTA1 and ANK1. Gilbert syndrome (GS) is a disease characterized by a mild deficiency of uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) enzyme activity and unconjugated hyperbilirubinemia, largely caused by UGT1A1 mutations. The two inherited diseases HS and GS are rarely occurred in the same patient and are easy to be misdiagnosed, resulting in excessive diagnosis and treatment. Here, we report a rare case of HS combined with GS due to mutations in the SPTB and UGT1A1 genes. A 50-year-old man who had an over 40-year history of jaundice was admitted to our hospital owing to fatigue and fever. His blood analysis showed low hemoglobin (74 g/L), high reticulocyte (23.5%) and high serum bilirubin (65 µmol/L); abdominal ultrasound revealed calculous cholecystitis and splenomegaly. Considering a possible diagnosis of hemolytic anemia, further examinations showed 42% spherocytes in blood smears and high erythroid lineage hyperplasia in bone marrow. Subsequently, 151 jaundice-related genes panel sequencing was done and results showed SPTB p.N1260fs and UGT1A1 p.G71R mutations. Then the patient was diagnosed with HS complicated with GS. Anti-infection and supportive treatments were providing to the patient, while infection removed, the hemoglobin recovered to normal, and no additional treatment was given. These findings of this report indicate that patients who are considered hemolytic anemia presenting with jaundice and anemia, genetic testing is a crucial method for the final diagnosis and bilirubin metabolic disease should also be concerned.

Efficacy and safety of telitacicept in IgA nephropathy: A retrospective, multicenter study.

Introduction The efficacy of Telitacicept treatment in reducing proteinuria in patients with IgA nephropathy (IgAN) was indicated in a phase II clinical trial with small sample size. In this study, we conducted a large multicenter retrospective study to explore the efficacy and safety of Telitacicept in patients with IgAN. Methods This study recruited patients with IgAN from 19 sites from China who were treated with Telitacicept and had been followed up at least once or with side effect reported, since April 1, 2021 to April 1, 2023. The primary outcomes of the study were the changing in proteinuria and eGFR over time. Results A cohort of 97 patients with IgAN who were treated with Telitacicept were recruited, with a median follow-up duration of 3 months. The median baseline proteinuria was 2.3 [1.3, 3.9] g/day and eGFR was 45.0 [26.8, 73.7] ml/min/1.73m2. There was a significant reduction of proteinuria at 2,4,6 months when compared with baseline (2.3 [1.5, 4.1] vs. 1.5 [0.8, 2.3] g/day; 2.3 [1.1, 3.7] vs. 1.1 [0.6, 1.9] g/day; 2.1 [1.0, 2.7] vs. 0.9 [0.5,1.7] g/day, all P values < 0.01). The level of eGFR were comparable between at the baseline and 2, 4, 6 months of follow-up time (41.5 [29.7, 72.0] vs. 42.5 [28.8, 73.3] ml/min/1.73m2; 41.0 [26.8, 67.7] vs. 44.7 [31.0, 67.8] ml/min/1.73m2; 33.7 [24.0, 58.5] vs. 32.6 [27.8, 57.5] ml/min/1.73m2, all P values > 0.26). Telitacicept was well tolerated in the patients. Conclusions This study indicates that Telitacicept alone or on top of steroids therapy can significantly and safely reduce proteinuria in patients with IgAN. The long-term kidney protection still need to be confirmed in large Phase III trial.

Discovery of TK-642 as a highly potent, selective, orally bioavailable pyrazolopyrazine-based allosteric SHP2 inhibitor.

Src homology-2-containing protein tyrosine phosphatase 2 (SHP2) is a promising therapeutic target for cancer therapy. In this work, we presented the structure-guided design of 5,6-fused bicyclic allosteric SHP2 inhibitors, leading to the identification of pyrazolopyrazine-based TK-642 as a highly potent, selective, orally bioavailable allosteric SHP2 inhibitor (SHP2WT IC50 = 2.7 nmol/L) with favorable pharmacokinetic profiles (F = 42.5%; t 1/2 = 2.47 h). Both dual inhibition biochemical assay and docking analysis indicated that TK-642 likely bound to the "tunnel" allosteric site of SHP2. TK-642 could effectively suppress cell proliferation (KYSE-520 cells IC50 = 5.73 µmol/L) and induce apoptosis in esophageal cancer cells by targeting the SHP2-mediated AKT and ERK signaling pathways. Additionally, oral administration of TK-642 also demonstrated effective anti-tumor effects in the KYSE-520 xenograft mouse model, with a T/C value of 83.69%. Collectively, TK-642 may warrant further investigation as a promising lead compound for the treatment of esophageal cancer.

Oxycodone vs. sufentanil combined with quadratus lumborum block vs. transverse abdominis plane block in laparoscopic major gastrointestinal surgery: A randomized factorial trial protocol.

Background: Multimodal analgesia plays a key role in enhanced recovery after surgery. Herein, we describe a trial protocol investigating the effects of oxycodone-vs. sufentanil-based patient-controlled analgesia in combination with quadratus lumborum block (QLB) vs. transverse abdominis plane block (TAPB) on quality of recovery following major laparoscopic gastrointestinal surgery. Methods: and analysis: This is a prospective, randomized, controlled clinical trial with a 2 × 2 factorial design. A total of 120 adult patients undergoing laparoscopic major gastrointestinal surgery will be randomized, in a 1:1:1:1 ratio, to receive one of two patient-controlled analgesia regimens (based on oxycodone or sufentanil) and one of two regional blocks (QLB or TAPB). The primary outcome measure of this trial is the quality of recovery at 24 h after surgery, assessed using the 15-item quality of recovery (QoR-15) scale. The secondary outcomes include QoR-15 scores at 48 and 72 h after surgery; visceral and incisional pain at rest and while coughing at 1, 6, 24 and 48 h postoperatively; analgesic consumption within 0-24 h and 24-48 h postoperatively; need for rescue analgesia; postoperative flatus time; postoperative adverse events (sedation, nausea and vomiting, use of antiemetics, respiratory depression, and dizziness); and length of postoperative hospital stay. Discussion: The results of this trial will provide evidence for the optimal multimodal analgesic strategy to improve the quality of recovery for patients undergoing laparoscopic major gastrointestinal surgery. Trial registration: This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn, identifier: ChiCTR2400080766).

The mechanism of action and chemical synthesis of FDA newly approved drug molecules.

In 2023, the U.S. Food and Drug Administration has approved 29 small molecule drugs. These newly approved small molecule drugs possess the distinct scaffolds, thereby exhibiting diverse mechanisms of action and binding modalities. Moreover, the marketed drugs have always been an important source of new drug development and creative inspiration, thereby fostering analogous endeavors in drug discovery that potentially extend to the diverse clinical indications. Therefore, conducting a comprehensive evaluation of drug approval experience and associated information will facilitate the expedited identification of highly potent drug molecules. In this review, we comprehensively summarized the relevant information regarding the clinical applications, mechanisms of action and chemical synthesis of 29 small molecule drugs, with the aim of providing a promising structural basis and design inspiration for pharmaceutical chemists.

The duct of von Ebner's glands is a source of Sox10 + taste bud progenitors and susceptible to pathogen infections.

Introduction: We have recently demonstrated that Sox10-expressing (Sox10 +) cells give rise to mainly type-III neuronal taste bud cells that are responsible for sour and salt taste. The two tissue compartments containing Sox10 + cells in the surrounding of taste buds include the connective tissue core of taste papillae and von Ebner's glands (vEGs) that are connected to the trench of circumvallate and foliate papillae. Methods: In this study, we performed single cell RNA-sequencing of the epithelium of Sox10-Cre/tdT mouse circumvallate/vEG complex and used inducible Cre mouse models to map the cell lineages of vEGs and/or connective tissue (including stromal and Schwann cells). Results: Transcriptomic analysis indicated that Sox10 expression was enriched in the cell clusters of vEG ducts that contained abundant proliferating cells, while Sox10-Cre/tdT expression was enriched in type-III taste bud cells and vEG ductal cells. In vivo lineage mapping showed that the traced cells were distributed in circumvallate taste buds concurrently with those in the vEGs, but not in the connective tissue. Moreover, multiple genes encoding pathogen receptors were enriched in the vEG ducts hosting Sox10 + cells. Discussion: Our data supports that it is the vEGs, not connective tissue core, that serve as the niche of Sox10 + taste bud progenitors. If this is also true in humans, our data indicates that vEG duct is a source of Sox10 + taste bud progenitors and susceptible to pathogen infections.

Sub-180-nanometer-thick ultraconformable high-performance carbon nanotube-based dual-gate transistors and differential amplifiers.

There is increased interest in ultrathin flexible devices with thicknesses of <1 micrometers due to excellent conformability toward advanced laminated bioelectronics. However, because of limitations in materials, device structure, and fabrication methodology, the performance of these ultrathin devices and circuits is insufficient to support higher-level applications. Here, we report high-performance carbon nanotube-based thin-film transistors (TFTs) and differential amplifiers on ultrathin polyimide films with a total thickness of <180 nanometers. A dual-gate structure is introduced to guarantee excellent gate control efficiency and mechanical stability of the ultrathin TFTs, which exhibit high transconductance (8.96 microsiemens per micrometer), high mobility (127 square centimeters per volt per second), and steep subthreshold swing (84 millivolts per decade), and can sustain a bending radius of curvature of <10 micrometers. The differential amplifier achieves the highest gain-bandwidth product (1.83 megahertz) among flexible differential amplifiers, enabling higher-gain amplification of weak signals over an extended frequency spectrum that is demonstrated by amplification of electromyography signals in situ.

High-order diffraction for optical superfocusing.

High-order diffraction (HOD) from optical microstructures is undesirable in many applications because of the accompanying ghosting patterns and loss of efficiency. In contrast to suppressing HOD with subwavelength structures that challenge the fabrication of large-scale devices, managing HOD is less developed due to the lack of an efficient method for independently manipulating HOD. Here, we report independent manipulation of HODs, which are unexploited for subdiffraction-limit focusing in diffractive lenses, through an analytical formula that correlates the diffraction order and the width of each zone. The large spatial frequencies offered by the HODs enable our lenses to reduce the lateral focal size down to 0.44 λ even without any subwavelength feature (indispensable in most high-NA diffractive lenses), facilitating large-scale manufacture. Experimentally, we demonstrate high-order lens-based confocal imaging with a center-to-center dry resolution of 190 nm, the highest among visible-light confocal microscopies, and laser-ablation lithography with achieved direct-writing resolution of 400 nm (0.385 λ).

Atomic Layer-Deposited Silane Coupling Agent for Interface Passivation of Quantum Dot Light-Emitting Diodes.

Inserting an insulating layer between the charge transport layer (CTL) and quantum dot emitting layer (QDL) is widely used in improving the performance of quantum dot light-emitting diodes (QLEDs). However, the additional layer inevitably leads to energy loss and joule heat. Herein, a monolayer silane coupling agent is used to modify the said interfaces via the self-limiting adsorption effect. Because the ultrathin layers induce negligible series resistance to the device, they can partially passivate the interfacial defects on the electron transport side and help confine the electrons within the QDL on the hole transport side. These interfacial modifications can not only suppress the nonradiative recombination but also slow down the aging of the hole transport layer. The findings here underline a low-temperature adsorption-based strategy for effective interfacial modification which can be used in any layer-by-layer device structures.

Superhydrophobic microporous membrane based on modified microfibrillated cellulose framework for efficient oil-water separation.

The preparation of stable and efficient cellulose-based oil/water separation membranes is of great significance in solving the problem of industrial oily wastewater. Herein, rod-like hydroxyapatite (HAP) modified microfibrillated celluloses (MFCs) are used to form the fibrous framework to produce a microporous PDMS-MFC-HAP membrane. The membrane shows good superhydrophobicity with a water contact angle of 151.6°. It exhibits the oil-water separation performance for various water-in-oil emulsions. The separation flux of the membrane is up to 3665.3 L·m-2·h-1·bar-1 under 0.5 bar pressure with a separation efficiency of over 99.6 %. The PDMS-MFC-HAP membrane could maintain a high separation efficiency of 98.6 % after 20 cycles. This study provides a simple and effective method to fabricate cellulose-based superhydrophobic membranes, which have a greater potential to achieve oil-water separation for oily wastewater treatment with high efficiency.

Zuogui Pills Improve the Learning and Memory Ability of Brain-Aging Mice through the Estrogen Receptor ERα Methylation Pathway.

INTRODUCTION: Sex hormones are important factors in maintaining brain function and acting as brain protectors. Recent research suggests that neuronal damage in brain aging may be linked to the methylation of the estrogen receptor α (ERα). However, the mechanism of Zuogui Pills (ZGW) in brain-aging ERα DNA methylation and neuronal repair remains unknown. MATERIALS AND METHODS: D-galactose-induced ovary removal mice were used as a model of aging. Changes in estrous cycle were detected in mice by vaginal cell smear. Animal behavior tests, including the Morris water maze (MWM) and new object recognition (NOR) test, were conducted. Hematoxylin-eosin (HE) and Nissl-staining were carried out to assess hippocampal neurogenesis. Enzyme-linked immunosorbent assay (ELISA) was performed for 5- methylcytosine methylation levels, and immunohistochemistry (IHC) and western blotting (WB) experiments were performed to assess ERα/DNA methyltransferase 1 (DNMT1) expression after ZGW treatment. Finally, bisulfite sequencing PCR (BSP) analysis was performed to identify methylated differentially expressed estrogen receptor 1 (ESR1) gene in D-gal-induced senescent neurons before and after ZGW treatment. RESULTS: We found that ERα methylation was involved in the delayed brain ageing process of ZGW. Mechanistically, ZGW can improve the learning and memory ability of brain-aging mice, reduce the expression of 5-methylcytosine (5-mc) in serum, increase the amount of ERα, inhibit the expression of DNMT1, and significantly reduce methylated expression of the ESRI gene. CONCLUSION: Our data suggested that ZGW slowed down D-gal-induced brain aging in mice, and these results showed that ZGW is beneficial for aging. It may be used for neuronal protection in aging.

Systemic immune-inflammation index combined with pediatric appendicitis score in assessing the severity and prognosis for paediatric appendicitis.

BACKGROUND: Pediatric appendicitis is a common cause of abdominal pain in children and is recognized as a significant surgical emergency. A prompt and accurate diagnosis is essential to prevent complications such as perforation and peritonitis. AIM: To investigate the predictive value of the systemic immune-inflammation index (SII) combined with the pediatric appendicitis score (PAS) for the assessment of disease severity and surgical outcomes in children aged 5 years and older with appendicitis. METHODS: Clinical data of 104 children diagnosed with acute appendicitis were analyzed. The participants were categorized into the acute appendicitis group and chronic appendicitis group based on disease presentation and further stratified into the good prognosis group and poor prognosis group based on prognosis. The SII and PAS were measured, and a joint model using the combined SII and PAS was constructed to predict disease severity and surgical outcomes. RESULTS: Significant differences were observed in the SII and PAS parameters between the acute appendicitis group and chronic appendicitis group. Correlation analysis showed associations among the SII, PAS, and disease severity, with the combined SII and PAS model demonstrating significant predictive value for assessing disease severity [aera under the curve (AUC) = 0.914] and predicting surgical outcomes (AUC = 0.857) in children aged 5 years and older with appendicitis. CONCLUSION: The study findings support the potential of integrating the SII with the PAS for assessing disease severity and predicting surgical outcomes in pediatric appendicitis, indicating the clinical utility of the combined SII and PAS model in guiding clinical decision-making and optimizing surgical management strategies for pediatric patients with appendicitis.

Near Stochiometric LiNbO3 Crystal: the Piezoelectric Features and the Shear Horizontal Guided Wave Transducer for Structural Health Monitoring up to 650 °C.

The application of shear horizontal (SH) guided wave transducers in high-temperature structural health monitoring (SHM) is a topic of significant interest across various industrial engineering sectors. In this study, we utilized the novelty piezoelectric crystal of near stoichiometric lithium niobate (NSLN), which exhibited a robust piezoelectric response (d15 = 77.6 pC/N@room temperature). Next, the pure thickness shear vibration mode d15' through size optimization was designed. It was demonstrated that the NSLN-based ultrasonic guided wave transducers utilizing the optimum d15' mode were proficient in transmitting and receiving pure fundamental SH wave (SH0 wave) along two orthogonal main directions (0° and 90°) over a wide frequency range (100-350 kHz), exhibiting strong response to the SH0 wave. Under the driving voltage of 100 V, the signal voltages of the NSLN-based transducer were found to be on the order of 200.3 and 11.8 mV at room temperature and high temperature of 650 °C, respectively. Moreover, the NSLN-based SH0 transducer showcased its better defect localization ability, and the signal-to-noise ratio (SNR) sensitivity of NSLN-based transducer was evaluated to be 16.1 dB at high temperature of 650 °C. To sum up, the ultrasonic wave transducer based on NSLN crystal demonstrated higher potential applications for in situ SHM under elevated temperatures.