Anterior Shoulder Stabilization Using Single Needle-Assisted Outside-In Remplissage Technique and Bankart Repair.

Arthroscopic repair of Bankart injury is the first choice for the treatment of anterior shoulder instability. How to avoid recurring shoulder joint dislocation is a challenge, especially when combined with Hill-Sachs lesions. The arthroscopy technology allows for broader vision and less surgical trauma but is limited by a smaller operating space. At present, extensive descriptions about the surgical procedure of arthroscopic Bankart repair have been published. In this Technical Note, we describe the use of remplissage filling with Hill-Sachs lesion combined with Bankart repair to further improve the surgical accuracy and clinical efficacy. In particular, the application of single needle-assisted outside-in remplissage technique and Bankart repair is introduced in detail.

Novel Synergistic Probiotic Intervention: Transcriptomic and Metabolomic Analysis Reveals Ameliorative Effects on Immunity, Gut Barrier, and Metabolism of Mice during Salmonella typhimurium Infection.

Salmonella typhimurium (S. typhimurium), a prevalent cause of foodborne infection, induces significant changes in the host transcriptome and metabolome. The lack of therapeutics with minimal or no side effects prompts the scientific community to explore alternative therapies. This study investigates the therapeutic potential of a probiotic mixture comprising Lactobacillus acidophilus (L. acidophilus 1.3251) and Lactobacillus plantarum (L. plantarum 9513) against S. typhimurium, utilizing transcriptome and metabolomic analyses, a novel approach that has not been previously documented. Twenty-four SPF-BALB/c mice were divided into four groups: control negative group (CNG); positive control group (CPG); probiotic-supplemented non-challenged group (LAPG); and probiotic-supplemented Salmonella-challenged group (LAPST). An RNA-sequencing analysis of small intestinal (ileum) tissue revealed 2907 upregulated and 394 downregulated DEGs in the LAPST vs. CPG group. A functional analysis of DEGs highlighted their significantly altered gene ontology (GO) terms related to metabolism, gut integrity, cellular development, and immunity (p ≤ 0.05). The KEGG analysis showed that differentially expressed genes (DEGs) in the LAPST group were primarily involved in pathways related to gut integrity, immunity, and metabolism, such as MAPK, PI3K-Akt, AMPK, the tryptophan metabolism, the glycine, serine, and threonine metabolism, ECM-receptor interaction, and others. Additionally, the fecal metabolic analysis identified 1215 upregulated and 305 downregulated metabolites in the LAPST vs. CPG group, implying their involvement in KEGG pathways including bile secretion, propanoate metabolism, arginine and proline metabolism, amino acid biosynthesis, and protein digestion and absorption, which are vital for maintaining barrier integrity, immunity, and metabolism. In conclusion, these findings suggest that the administration of a probiotic mixture improves immunity, maintains gut homeostasis and barrier integrity, and enhances metabolism in Salmonella infection.

Physeal-Sparing, All-Inside Anterior Cruciate Ligament Reconstruction Using Quadrupled Semitendinosus Autograft and Suture Tape Augmentation for Skeletally Immature Patients.

The anterior cruciate ligament (ACL) is the primary soft-tissue structure for anterior stabilization of the knee and is one of the most frequently injured structures. The incidence of ACL injuries in children and adolescents ranges from 92 to 151 per 100,000 person-years. The choice of surgical treatment for this population group is controversial, with a widespread concern that adult reconstruction techniques may damage the epiphyseal plate, compromise growth, or cause deformity. In this article, we describe a physeal-sparing, all-inside ACL reconstruction technique for skeletally immature patients. This technique is supported by retrograde drilling of the femoral tunnel and retrograde drilling of the tibial tunnel, both of which are able to avoid the epiphyseal growth line. Fixation of the quadrupled semitendinosus autograft and suture tape augmentation are achieved by soft-tissue buttons on the femur and tibia. The surgical details of this reproducible reconstruction technique are elaborated.

Screening and Diagnosis of Rare Thalassemia Variants: Is Third-Generation Sequencing Enough?

CONTEXT.­: Rare thalassemia subtypes are often undiagnosed because conventional testing methods can only identify 23 common types of α- and ß-thalassemia. OBJECTIVE.­: To assess a comprehensive approach for the screening and diagnosis of rare thalassemia. DESIGN.­: The study cohort included 72 individuals with suspected rare thalassemia variants. Screening was conducted by next-generation sequencing (NGS) combined with third-generation sequencing (TGS) and chromosomal microarray analysis (CMA)/copy number variation sequencing. RESULTS.­: Of the 72 individuals with suspected rare thalassemia, 49 had rare α- or ß-gene variants. NGS combined with gap polymerase chain reaction detected a total of 42 cases, resulting in a positive detection rate of 58.3%. Additionally, 4 α-globin genetic deletions were identified by TGS, which increased the variant detection rate by 5.6%. Two samples with a microdeletion of chromosome 16 or 11 were detected by CMA, which increased the detection rate by 2.8%. For one sample, reanalysis of the NGS and TGS data confirmed the presence of the ß41-42/ßN and ßN/ßN mosaic. The HBB:c.315 + 2delT mutation was initially reported in Guangdong Province, China. Two HBB gene mutations (HBB:c.315 + 5G>C and HBB:c.295G>A) and 4 rare HBA gene deletions (-11.1, -α27.6, -α2.4, and -α21.9) were initially identified in the Zhonshan region. The hematologic phenotypes of all rare cases in this study were clarified. CONCLUSIONS.­: Rare thalassemia variants are more common than previously thought. Despite advancements in TGS, there is still no foolproof method for detection of all types of thalassemia. Thus, a comprehensive approach is necessary for accurate screening and diagnosis of rare thalassemia variants.

First-in-human phase I study of BEBT-109 in previously treated EGFR exon 20 insertion-mutated advanced non-small cell lung cancer.

BACKGROUND: BEBT-109 is an oral pan-mutant-selective inhibitor of epidermal growth factor receptor (EGFR) that demonstrated promising antitumor potency in preclinical models. METHODS: This first-in-human study was a single-arm, open-label, two-stage study. Phase Ia dose-escalation study evaluated the safety and pharmacokinetics of BEBT-109 in 11 patients with EGFR T790M-mutated advanced non-small cell lung cancer (aNSCLC). Phase Ib dose-expansion study evaluated the safety and efficacy of BEBT-109 in 18 patients with EGFR exon 20 insertion (ex20ins)-mutated treatment-refractory aNSCLC. The primary outcomes were adverse events and antitumor activity. Clinical trial registration number CTR20192575. FINDINGS: The phase Ia study demonstrated no dose-limiting toxicity, no observation of the maximum tolerated dose, and no new safety signals with BEBT-109 in the dose range of 20-180 mg/d, suggesting that BEBT-109 had an acceptable safety profile among patients with EGFR T790M-mutated aNSCLC. Plasma pharmacokinetics of BEBT-109 showed a dose-proportional increase in the area under the curve and maximal concentration, with no significant drug accumulation. The dose-expansion study demonstrated that BEBT-109 treatment was tolerable across the three dose levels. The three most common treatment-related adverse events were diarrhea (100%; 22.2% ≥Grade 3), rash (66.7%; 5.6% ≥Grade 3), and anemia (61.1%; 0% ≥Grade 3). The objective response rate was 44.4% (8 of 18). Median progression-free survival was 8.0 months (95% confidence intervals, 1.33-14.67). CONCLUSION: Preliminary findings showed that BEBT-109 had an acceptable safety profile and favorable antitumor activity in patients with refractory EGFR ex20ins-mutated aNSCLC. FUNDING: National Natural Science Foundation of China.

scDOT: enhancing single-cell RNA-Seq data annotation and uncovering novel cell types through multi-reference integration.

The proliferation of single-cell RNA-seq data has greatly enhanced our ability to comprehend the intricate nature of diverse tissues. However, accurately annotating cell types in such data, especially when handling multiple reference datasets and identifying novel cell types, remains a significant challenge. To address these issues, we introduce Single Cell annotation based on Distance metric learning and Optimal Transport (scDOT), an innovative cell-type annotation method adept at integrating multiple reference datasets and uncovering previously unseen cell types. scDOT introduces two key innovations. First, by incorporating distance metric learning and optimal transport, it presents a novel optimization framework. This framework effectively learns the predictive power of each reference dataset for new query data and simultaneously establishes a probabilistic mapping between cells in the query data and reference-defined cell types. Secondly, scDOT develops an interpretable scoring system based on the acquired probabilistic mapping, enabling the precise identification of previously unseen cell types within the data. To rigorously assess scDOT's capabilities, we systematically evaluate its performance using two diverse collections of benchmark datasets encompassing various tissues, sequencing technologies and diverse cell types. Our experimental results consistently affirm the superior performance of scDOT in cell-type annotation and the identification of previously unseen cell types. These advancements provide researchers with a potent tool for precise cell-type annotation, ultimately enriching our understanding of complex biological tissues.

Electrothermally controlled origami fabricated by 4D printing of continuous fiber-reinforced composites.

Active origami capable of precise deployment control, enabling on-demand modulation of its properties, is highly desirable in multi-scenario and multi-task applications. While 4D printing with shape memory composites holds great promise to realize such active origami, it still faces challenges such as low load-bearing capacity and limited transformable states. Here, we report a fabrication-design-actuation method of precisely controlled electrothermal origami with excellent mechanical performance and spatiotemporal controllability, utilizing 4D printing of continuous fiber-reinforced composites. The incorporation of continuous carbon fibers empowers electrothermal origami with a controllable actuation process via Joule heating, increased actuation force through improved heat conduction, and enhanced mechanical properties as a result of reinforcement. By modeling the multi-physical and highly nonlinear deploying process, we attain precise control over the active origami, allowing it to be reconfigured and locked into any desired configuration by manipulating activation parameters. Furthermore, we showcase the versatility of electrothermal origami by constructing reconfigurable robots, customizable architected materials, and programmable wings, which broadens the practical engineering applications of origami.

ReHoGCNES-MDA: prediction of miRNA-disease associations using homogenous graph convolutional networks based on regular graph with random edge sampler.

Numerous investigations increasingly indicate the significance of microRNA (miRNA) in human diseases. Hence, unearthing associations between miRNA and diseases can contribute to precise diagnosis and efficacious remediation of medical conditions. The detection of miRNA-disease linkages via computational techniques utilizing biological information has emerged as a cost-effective and highly efficient approach. Here, we introduced a computational framework named ReHoGCNES, designed for prospective miRNA-disease association prediction (ReHoGCNES-MDA). This method constructs homogenous graph convolutional network with regular graph structure (ReHoGCN) encompassing disease similarity network, miRNA similarity network and known MDA network and then was tested on four experimental tasks. A random edge sampler strategy was utilized to expedite processes and diminish training complexity. Experimental results demonstrate that the proposed ReHoGCNES-MDA method outperforms both homogenous graph convolutional network and heterogeneous graph convolutional network with non-regular graph structure in all four tasks, which implicitly reveals steadily degree distribution of a graph does play an important role in enhancement of model performance. Besides, ReHoGCNES-MDA is superior to several machine learning algorithms and state-of-the-art methods on the MDA prediction. Furthermore, three case studies were conducted to further demonstrate the predictive ability of ReHoGCNES. Consequently, 93.3% (breast neoplasms), 90% (prostate neoplasms) and 93.3% (prostate neoplasms) of the top 30 forecasted miRNAs were validated by public databases. Hence, ReHoGCNES-MDA might serve as a dependable and beneficial model for predicting possible MDAs.

PLMSearch: Protein language model powers accurate and fast sequence search for remote homology.

Homologous protein search is one of the most commonly used methods for protein annotation and analysis. Compared to structure search, detecting distant evolutionary relationships from sequences alone remains challenging. Here we propose PLMSearch (Protein Language Model), a homologous protein search method with only sequences as input. PLMSearch uses deep representations from a pre-trained protein language model and trains the similarity prediction model with a large number of real structure similarity. This enables PLMSearch to capture the remote homology information concealed behind the sequences. Extensive experimental results show that PLMSearch can search millions of query-target protein pairs in seconds like MMseqs2 while increasing the sensitivity by more than threefold, and is comparable to state-of-the-art structure search methods. In particular, unlike traditional sequence search methods, PLMSearch can recall most remote homology pairs with dissimilar sequences but similar structures. PLMSearch is freely available at https://dmiip.sjtu.edu.cn/PLMSearch .

Non-enzymatic Detection of Uric Acid in Serum and Urine by Fluorescent and Visual Dual-Mode Sensor Based on 3-aminophenylboric Acid Functionalized Carbon Dots.

Herein, we developed a sophisticated dual-mode sensor that utilized 3-aminophenylboric acid functionalized carbon dots (APBA-CDs) to accurately detect uric acid (UA). Our innovative process involved synthesizing APBA-CDs that emitted at 369 nm using a one-step hydrothermal method with 3-aminophenylboric acid and L-glutamine as precursors, ethanol and deionized water as solvents. Once UA was introduced to the APBA-CDs, the fluorescence of the system became visibly quenched. The results of Zeta potential, Fourier transformed infrared (FTIR) spectra, fluorescence lifetime, and other characteristics were analyzed to determine that the reaction mechanism was static quenching. This meant that after UA was mixed with APBA-CDs, it combined with the boric acid function on the surface to form complexes, resulting in a decrease in fluorescence intensity and a blue shift in the absorption peak at about 295 nm in the Ultraviolet-visible (UV-vis) absorption spectra. We were pleased to report that we have successfully used the dual-reading platform to accurately detect UA in serum and human urine. It provided a superior quantitative and visual analysis of UA without the involvement of enzymes. We firmly believe that our innovative dual-mode sensor has immense potential in the fields of biosensing and health monitoring.

Optimization of ultrasound-assisted extraction of Imperata cylindrica polysaccharides and evaluation of its anti-oxidant and amelioration of uric acid stimulated cell apoptosis.

An efficient, cost-effective and environmentally friendly ultrasound-assisted hot water method for Imperata cylindrica polysaccharide (ICPs) extraction was developed. According to the response surface results, the optimal ultrasonic time was 85 min, ultrasonic power was 192.75 W, temperature was 90.74 °C, liquid-solid ratio was 26.1, and polysaccharide yield was 28.50 %. The polysaccharide mainly consisted of arabinose (Ara), galactose (Gal), and glucose (Glc), with a molecular weight of 62.3 kDa. Ultrasound-assisted extraction of Imperata cylindrica polysaccharide (UICP) exhibited stronger anti-oxidant activity and ability to ameliorate cellular damage due to uric acid stimulation compared with traditional hot water extraction of Imperata cylindrica polysaccharide (ICPC-b). It also exhibited higher thermal stability, indicating its potential value for applications in the food industry.

Nitrogen and Sulfur co-doped Carbon dots as an "on-off-on" Fluorescent Sensor for the Detection of Hg2+ and Ampicillin.

Herein, a fluorescent "on-off-on" nanosensor based on N,S-CDs was developed for highly precise and sensitive recognition of Hg2+ and ampicillin (AMP). Nitrogen and sulfur co-doped carbon dots with blue fluorescence were synthesized by one-pot hydrothermal method using ammonium citrate and DL-methionine as precursors. N,S-CDs exhibited a surface abundant in -OH, -COOH, and -NH2 groups, aiding in creating non-fluorescent ground state complexes when combined with Hg2+, leading to the suppression of N,S-CDs' fluorescence. Subsequent to additional AMP application, the mixed system's fluorescence was restored. Based on this N,S-CDs sensing system, the thresholds for detection for AMP and Hg2+ were discovered to be 0.121 µM and 0.493 µM, respectively. Furthermore, this methodology proved effective in identifying AMP in real samples of tap and lake water, yielding satisfactory results. Consequently, in the area of bioanalysis in intricate environmental sample work, the sensing system showed tremendous promise.

CloudProteoAnalyzer: scalable processing of big data from proteomics using cloud computing.

Summary: Shotgun proteomics is widely used in many system biology studies to determine the global protein expression profiles of tissues, cultures, and microbiomes. Many non-distributed computer algorithms have been developed for users to process proteomics data on their local computers. However, the amount of data acquired in a typical proteomics study has grown rapidly in recent years, owing to the increasing throughput of mass spectrometry and the expanding scale of study designs. This presents a big data challenge for researchers to process proteomics data in a timely manner. To overcome this challenge, we developed a cloud-based parallel computing application to offer end-to-end proteomics data analysis software as a service (SaaS). A web interface was provided to users to upload mass spectrometry-based proteomics data, configure parameters, submit jobs, and monitor job status. The data processing was distributed across multiple nodes in a supercomputer to achieve scalability for large datasets. Our study demonstrated SaaS for proteomics as a viable solution for the community to scale up the data processing using cloud computing. Availability and implementation: This application is available online at https://sipros.oscer.ou.edu/ or https://sipros.unt.edu for free use. The source code is available at https://github.com/Biocomputing-Research-Group/CloudProteoAnalyzer under the GPL version 3.0 license.

Bioactivities and Action Mechanisms of Ellipticine Derivatives Reported Prior to 2023.

Currently, natural products are one of the priceless options for finding novel chemical pharmaceutical entities. Ellipticine is a naturally occurring alkaloid isolated from the leaves of Ochrosia elliptica Labill. Ellipticine and its derivatives are characterized by multiple biological activities. The purpose of this review was to provide a critical and systematic assessment of ellipticine and its derivatives as bioactive molecules over the last 60 years. Publications focused mainly on the total synthesis of alkaloids of this type without any evaluation of bioactivity have been excluded. We have reviewed papers dealing with the synthesis, bioactivity evaluation and mechanism of action of ellipticine and its derivatives. It was found that ellipticine and its derivatives showed cytotoxicity, antimicrobial ability, and anti-inflammatory activity, among which cytotoxicity toward cancer cell lines was the most investigated aspect. The inhibition of DNA topoisomerase II was the most relevant mechanism for cytotoxicity. The PI3K/AKT pathway, p53 pathway, and MAPK pathway were also closely related to the antiproliferative ability of these compounds. In addition, the structure-activity relationship was deduced, and future prospects were outlined. We are confident that these findings will lay a scientific foundation for ellipticine-based drug development, especially for anticancer agents.

Bioaccumulation and Male Reproductive Toxicity of the New Brominated Flame Retardant Tetrabromobisphenol A-Bis(2,3-dibromo-2-methylpropyl ether) in Comparison with Hexabromocyclododecane.

Tetrabromobisphenol A-bis(2,3-dibromo-2-methylpropyl ether) (TBBPA-DBMPE) has come into use as an alternative to hexabromocyclododecane (HBCD), but it is unclear whether TBBPA-DBMPE has less hazard than HBCD. Here, we compared the bioaccumulation and male reproductive toxicity between TBBPA-DBMPE and HBCD in mice following long-term oral exposure after birth. We found that the concentrations of TBBPA-DBMPE in livers significantly increased with time, exhibiting a bioaccumulation potency not substantially different from HBCD. Lactational exposure to 1000 µg/kg/d TBBPA-DBMPE as well as 50 µg/kg/d HBCD inhibited testis development in suckling pups, and extended exposure up to adulthood resulted in significant molecular and cellular alterations in testes, with slighter effects of 50 µg/kg/d TBBPA-DBMPE. When exposure was extended to 8 month age, severe reproductive impairments including reduced sperm count, increased abnormal sperm, and subfertility occurred in all treated animals, although 50 µg/kg/d TBBPA-DBMPE exerted lower effects than 50 µg/kg/d HBCD. Altogether, all data led us to conclude that TBBPA-DBMPE exerted weaker male reproductive toxicity than HBCD at the same doses but exhibited bioaccumulation potential roughly equivalent to HBCD. Our study fills the data gap regarding the bioaccumulation and toxicity of TBBPA-DBMPE and raises concerns about its use as an alternative to HBCD.

Genome-Wide Analysis of the Oat (Avena sativa) HSP90 Gene Family Reveals Its Identification, Evolution, and Response to Abiotic Stress.

Oats (Avena sativa) are an important cereal crop and cool-season forage worldwide. Heat shock protein 90 (HSP90) is a protein ubiquitously expressed in response to heat stress in almost all plants. To date, the HSP90 gene family has not been comprehensively reported in oats. Herein, we have identified twenty HSP90 genes in oats and elucidated their evolutionary pathways and responses to five abiotic stresses. The gene structure and motif analyses demonstrated consistency across the phylogenetic tree branches, and the groups exhibited relative structural conservation. Additionally, we identified ten pairs of segmentally duplicated genes in oats. Interspecies synteny analysis and orthologous gene identification indicated that oats share a significant number of orthologous genes with their ancestral species; this implies that the expansion of the oat HSP90 gene family may have occurred through oat polyploidization and large fragment duplication. The analysis of cis-acting elements revealed their influential role in the expression pattern of HSP90 genes under abiotic stresses. Analysis of oat gene expression under high-temperature, salt, cadmium (Cd), polyethylene glycol (PEG), and abscisic acid (ABA) stresses demonstrated that most AsHSP90 genes were significantly up-regulated by heat stress, particularly AsHSP90-7, AsHSP90-8, and AsHSP90-9. This study offers new insights into the amplification and evolutionary processes of the AsHSP90 protein, as well as its potential role in response to abiotic stresses. Furthermore, it lays the groundwork for understanding oat adaptation to abiotic stress, contributing to research and applications in plant breeding.

Dietary Paper Mulberry Silage Supplementation Improves the Growth Performance, Carcass Characteristics, and Meat Quality of Yangzhou Goose.

There have been few investigations into the health benefits and meat quality of supplementing Yangzhou geese with paper mulberry silage. One hundred and twenty 28-day-old Yangzhou geese were selected for the experiment and randomly divided into two groups: a control group (CON) and a paper mulberry silage group (PM), with six replicates in each group. The experiment lasted for a total of 6 weeks. The experiment found that compared with CON, PM had a promoting effect on the average daily weight gain of Yangzhou geese (p = 0.056). Sensory and nutritional analysis of breast muscles revealed a decrease in a* value (p < 0.05) and an increase in protein content (p < 0.05) following PM treatment. Through untargeted metabolomics analysis of breast muscle samples, it was found that 11 different metabolites, including guanidinoacetic acid and other substances, had a positive effect on amino acid metabolism and lipid antioxidant pathways of PM treatment. Overall, the strategy of feeding Yangzhou geese with paper mulberry silage is feasible, which can improve the sensory quality and nutritional value of goose meat. The experiment provides basic data for the application form of goose breeding, so exploring the impact of substances within paper mulberry on goose meat should be focused on in the future.

Improvement of surface stability of Zn anode by a cost-effective ErCl3 additive for realizing high-performance aqueous zinc-ion batteries.

Rechargeable aqueous-zinc ion batteries (AZIB) have notable benefits in terms of high safety and low cost. Nevertheless, the challenges, such as dendrite growth, zinc anode corrosion, and hydrogen evolution reaction, impede its practical implementation. Hence, this study proposes the introduction of an economical ErCl3 electrolyte additive to stabilize the Zn anode surface and address the aforementioned issues. The introduced Er3+ will cover the raised zinc dendrite surface and weaken the "tip effect" on the surface of the zinc anode via the "electrostatic shielding" effect. Simultaneously, the introduced Cl- can reduce the polarization of the zinc anode. Due to the synergistic effect of Er3+ and Cl-, the zinc anode corrosion, dendrite growth and hydrogen evolution have been efficiently inhibited. As a result, the Zn||Zn-symmetric battery using ErCl3 additive can stably cycle for 1100 h at 1 mA cm-2, 1 mAh cm-2, and exhibit a high average coulomb efficiency (99.2 %). Meanwhile, Zn||MnO2 full battery based on ErCl3-added electrolyte also demonstrates a high reversible capacity of 157.1 mAh/g after 500 cycles. Obviously, the capacity decay rate of the full battery is also improved, only 0.113 % per cycle. This study offers a straightforward and economically efficient method for stabilizing the zinc anode and realizing high-performance AZIBs.

Interposition Grafting Using Fascia Lata Autograft for Failed Rotator Cuff Repairs.

Massive rotator cuff tears are a huge challenge for orthopaedic surgeons, as the patients may be in need of multiple operations, even including reverse total shoulder arthroplasty. The various repair methods for the rotator cuff, such as partial rotator cuff repair, patch-augmented rotator cuff repair, bridging rotator cuff reconstruction with graft interposition, tendon transfer, and superior capsular reconstruction, have always been the focus of research. During surgical intervention for failed rotator cuff repairs, complexity of tears, poor tissue quality, retained hardware, and adhesions are the problems routinely encountered. In this Technical Note, we describe the technique of interposition grafting using fascia lata autograft to reconstruct the rotator cuff after failed primary repair.