An ATP13A1-assisted topogenesis pathway for folding multi-spanning membrane proteins.

Many multi-spanning membrane proteins contain poorly hydrophobic transmembrane domains (pTMDs) protected from phospholipid in mature structure. Nascent pTMDs are difficult for translocon to recognize and insert. How pTMDs are discerned and packed into mature, muti-spanning configuration remains unclear. Here, we report that pTMD elicits a post-translational topogenesis pathway for its recognition and integration. Using six-spanning protein adenosine triphosphate-binding cassette transporter G2 (ABCG2) and cultured human cells as models, we show that ABCG2's pTMD2 can pass through translocon into the endoplasmic reticulum (ER) lumen, yielding an intermediate with inserted yet mis-oriented downstream TMDs. After translation, the intermediate recruits P5A-ATPase ATP13A1, which facilitates TMD re-orientation, allowing further folding and the integration of the remaining lumen-exposed pTMD2. Depleting ATP13A1 or disrupting pTMD-characteristic residues arrests intermediates with mis-oriented and exposed TMDs. Our results explain how a "difficult" pTMD is co-translationally skipped for insertion and post-translationally buried into the final correct structure at the late folding stage to avoid excessive lipid exposure.

SRSF2 plays an unexpected role as reader of m5C on mRNA, linking epitranscriptomics to cancer.

A common mRNA modification is 5-methylcytosine (m5C), whose role in gene-transcript processing and cancer remains unclear. Here, we identify serine/arginine-rich splicing factor 2 (SRSF2) as a reader of m5C and impaired SRSF2 m5C binding as a potential contributor to leukemogenesis. Structurally, we identify residues involved in m5C recognition and the impact of the prevalent leukemia-associated mutation SRSF2P95H. We show that SRSF2 binding and m5C colocalize within transcripts. Furthermore, knocking down the m5C writer NSUN2 decreases mRNA m5C, reduces SRSF2 binding, and alters RNA splicing. We also show that the SRSF2P95H mutation impairs the ability of the protein to read m5C-marked mRNA, notably reducing its binding to key leukemia-related transcripts in leukemic cells. In leukemia patients, low NSUN2 expression leads to mRNA m5C hypomethylation and, combined with SRSF2P95H, predicts poor outcomes. Altogether, we highlight an unrecognized mechanistic link between epitranscriptomics and a key oncogenesis driver.

Layer-Dependent Superconductivity in Iron-Based Superconductors CsCa2Fe4As4F2 and CaKFe4As4.

In the quasi-two-dimensional superconductor NbSe2, the superconducting transition temperature (Tc) is layer-dependent, decreasing by about 60% in the monolayer limit. However, for the extremely anisotropic copper-based high-Tc superconductor Bi2Sr2CaCu2O8+δ (Bi-2212), the Tc of the monolayer is almost identical with that of its bulk counterpart. To clarify the effect of dimensionality on superconductivity, here, we successfully fabricate ultrathin flakes of iron-based high-Tc superconductors CsCa2Fe4As4F2 and CaKFe4As4. It is found that the Tc of monolayer CsCa2Fe4As4F2 (after tuning to the optimal doping by ionic liquid gating) is about 20% lower than that of the bulk crystal, while the Tc of three-layer CaKFe4As4 decreases by 46%, showing a more pronounced dimensional effect than that of CsCa2Fe4As4F2. By carefully examining their anisotropy and the c-axis coherence length, we reveal the general trend and empirical law of the layer-dependent superconductivity in these quasi-two-dimensional superconductors.

Characteristics and outcomes of COVID-19 in Chinese immune thrombocytopenia patients: A prospective cohort study.

The coronavirus disease 2019 (COVID-19) pandemic has a significant impact on the immune system. This is the first and largest study on pre-existing immune thrombocytopenia (ITP) patients infected with COVID-19 in China. We prospectively collected ITP patients infected with COVID-19 enrolled in the National Longitudinal Cohort of Hematological Diseases (NICHE, NCT04645199) and followed up for at least 1 month after infection. One thousand and one hundred forty-eight pre-existing ITP patients were included. Two hundred and twelve (18.5%) patients showed a decrease in the platelet (PLT) count after infection. Forty-seven (4.1%) patients were diagnosed with pneumonia. Risk factors for a decrease in the PLT count included baseline PLT count <50 × 109/L (OR, 1.76; 95% CI, 1.25-2.46; p = 0.001), maintenance therapy including thrombopoietin receptor agonists (TPO-RAs) (OR, 2.27; 95% CI, 1.60-3.21; p < 0.001) and previous splenectomy (OR, 1.98; 95% CI, 1.09-3.61; p = 0.03). Risk factors for pneumonia included age ≥40 years (OR, 2.45; 95% CI, 1.12-5.33; p = 0.02), ≥2 comorbidities (OR, 3.47; 95% CI, 1.63-7.64; p = 0.001), maintenance therapy including TPO-RAs (OR, 2.14; 95% CI, 1.17-3.91; p = 0.01) and immunosuppressants (OR, 3.05; 95% CI, 1.17-7.91; p = 0.02). In this cohort study, we described the characteristics of pre-existing ITP patients infected with COVID-19 and identified several factors associated with poor outcomes.

Highly Sensitive Wearable Sensor Based on (001)-Orientated TiO2 for Real-Time Electrochemical Detection of Dopamine, Tyrosine, and Paracetamol.

The concentration of dopamine (DA) and tyrosine (Tyr) reflects the condition of patients with Parkinson's disease, whereas moderate paracetamol (PA) can help relieve their pain. Therefore, real-time measurements of these bioanalytes have important clinical implications for patients with Parkinson's disease. However, previous sensors suffer from either limited sensitivity or complex fabrication and integration processes. This work introduces a simple and cost-effective method to prepare high-quality, flexible titanium dioxide (TiO2) thin films with highly reactive (001)-facets. The as-fabricated TiO2 film supported by a carbon cloth electrode (i.e., TiO2-CC) allows excellent electrochemical specificity and sensitivity to DA (1.390 µA µM-1 cm-2), Tyr (0.126 µA µM-1 cm-2), and PA (0.0841 µA µM-1 cm-2). More importantly, accurate DA concentration in varied pH conditions can be obtained by decoupling them within a single differential pulse voltammetry measurement without additional sensing units. The TiO2-CC electrochemical sensor can be integrated into a smart diaper to detect the trace amount of DA or an integrated skin-interfaced patch with microfluidic sampling and wireless transmission units for real-time detection of the sweat Try and PA concentration. The wearable sensor based on TiO2-CC prepared by facile manufacturing methods holds great potential in the daily health monitoring and care of patients with neurological disorders.

A conserved protein disulfide isomerase enhances plant resistance against herbivores.

Herbivore-associated molecular patterns (HAMPs) enable plants to recognize herbivores and may help plants adjust their defense responses. Here, we report on herbivore-induced changes in a protein disulfide isomerase (PDI) widely distributed across arthropods. PDI from the spider mite Tetranychus evansi (TePDI), a mesophyll-feeding agricultural pest worldwide, triggered immunity in multiple Solanaceae plants. TePDI-mediated cell death in Nicotiana benthamiana required the plant signaling proteins SGT1 (suppressor of the G2 allele of skp1) and HSP90 (heat shock protein 90), but was suppressed by spider mite effectors Te28 and Te84. Moreover, PDIs from phylogenetically distinct herbivorous and nonherbivorous arthropods triggered plant immunity. Finally, although PDI-induced plant defenses impaired the performance of spider mites on plants, RNAi experiments revealed that PDI genes are essential for the survival of mites and whiteflies. Our findings indicate that plants recognize evolutionarily conserved HAMPs to activate plant defense and resist pest damage, pointing to opportunities for broad-spectrum pest management.

Emerging Roles of RNA Methylation in Development.

More than 170 different types of chemical modifications have been identified on diverse types of RNA, collectively known as the epitranscriptome. Among them, N6-methyladenine (m6A), 5-methylcytosine (m5C), N1-methyladenine (m1A), and N7-methylguanosine (m7G) as the ubiquitous post-transcriptional modification are widely involved in regulating the metabolic processes such as RNA degradation, translation, stability, and export, mediating important physiological and pathological processes such as stress regulation, immune response, development, and tumorigenesis. Recently, the regulatory role of RNA modification during developmental processes is getting more attention. Therefore, the development of low-input even single-cell and high-resolution sequencing technologies is crucial for the exploration of the regulatory roles of RNA modifications in these important biological events of trace samples.This account focuses on the roles of RNA modifications in various developmental processes. We describe the distribution characteristics of various RNA modifications, catalytic enzymes, binding proteins, and the development of sequencing technologies. RNA modification is dynamically reversible, which can be catalyzed by methyltransferases and eliminated by demethylases. RNA m6A is the most abundant post-transcriptional modification on eukaryote mRNA, which is mainly concentrated near the stop codon, and involves in RNA metabolism regulation. RNA m5C, another most studied RNA modification, has been identified in a various of organisms and RNA species, mainly enriched in the regions downstream of translation initiation sites and broadly distributes across the whole coding sequence (CDS) in mammalian mRNAs. RNA m1A, with a lower abundance than m6A, is widely distributed in various RNA types, mainly locates in the 5' untranslated region (5'UTR) of mRNA and regulates translation. RNA m7G, one of the most common RNA modifications in eukaryotes, has been identified at cap regions and internal positions of RNAs and recently gained considerable attention.Thanks to the development of sequencing technology, m6A has been found to regulate the tumorigenic process, including tumor proliferation, invasion, and metastasis by modulating oncogenes and tumor suppressor genes, and affect oocyte maturation and embryonic development through regulating maternal and zygotic genes. m5C related proteins have been identified to participate in embryonic development, plant growth, and neural stem cell differentiation in a m5C dependent manner. m1A also has been revealed to be involved in these developmental processes. m7G dysregulation mainly involves in neurodevelopmental disorders and neurodegenerative diseases.Collectively, we summarized the gradually exhibited roles of RNA methylation during development, and discussed the possibility of RNA modifications as candidate biomarkers and potential therapeutic targets. The technological development is anticipated as the major driving force to expand our knowledge in this field.

Hyperbaric Oxygen Therapy Attenuated the Motor Coordination and Cognitive Impairment of Polyglutamine Spinocerebellar Ataxia SCA17 Mice.

Spinocerebellar ataxias (SCAs) are a large and diverse group of autosomal-dominant neurodegenerative diseases. No drugs have been approved for these relentlessly progressive and fatal SCAs. Our previous studies indicate that oxidative stress, neuroinflammation, and neuronal apoptosis are elevated in the SCA17 mice, which are the main therapeutic targets of hyperbaric oxygen treatment (HBOT). HBOT is considered to be an alternative and less invasive therapy for SCAs. In this study, we evaluated the HBOT (2.2 ATA for 14 days) effect and the persistence for the management of SCA17 mice and their wild-type littermates. We found HBOT attenuated the motor coordination and cognitive impairment of SCA17 mice and which persisted for about 1 month after the treatment. The results of several biochemistry and liver/kidney hematoxylin and eosin staining show the HBOT condition has no obvious toxicity in the mice. Immunostaining analyses show that the neuroprotective effect of HBOT could be through the promotion of BDNF production and the amelioration of neuroinflammation. Surprisingly, HBOT executes different effects on the male and female SCA17 mice, including the reduction of neuroinflammation and activation of CaMKII and ERK. This study suggests HBOT is a potential alternative therapeutic treatment for SCA17. Accumulated findings have revealed the similarity in disease pathomechanisms and possible therapeutic strategies in polyQ diseases; therefore, HBOT could be an optional treatment as well as the other polyQ diseases.

Rationalization of passivation strategies toward high-performance perovskite solar cells.

Lead halide perovskite solar cells (PSCs) have shown unprecedented development in efficiency and progressed relentlessly in improving stability. All the achievements have been accompanied by diverse passivation strategies to circumvent the pervasive defects in perovskite materials, which play crucial roles in the process of charge recombination, ion migration, and component degradation. Among the tremendous efforts made to solve these issues and achieve high-performance PSCs, we classify and review both well-established and burgeoning passivation strategies to provide further guidance for the passivation protocols in PSCs, including chemical passivation to eliminate defects by the formation of chemical bonds, physical passivation to eliminate defects by strain relaxation or physical treatments, energetic passivation to improve the stability toward light and oxygen, and field-effect passivation to regulate the interfacial carrier behavior. The subtle but non-trivial consequences from various passivation strategies need advanced characterization techniques combining synchrotron-based X-ray analysis, capacitance-based measurements, spatially resolved imaging, fluorescent molecular probe, Kelvin probe force microscope, etc., to scrutinize the mechanisms. In the end, challenges and prospective research directions on advancing these passivation strategies are proposed. Judicious combinations among chemical, physical, energetic, and field-effect passivation deserve more attention for future high-efficiency and stable perovskite photovoltaics.

Systematic Review of Machine Learning Applied to the Secondary Prevention of Ischemic Stroke.

Ischemic stroke is a serious disease posing significant threats to human health and life, with the highest absolute and relative risks of a poor prognosis following the first occurrence, and more than 90% of strokes are attributable to modifiable risk factors. Currently, machine learning (ML) is widely used for the prediction of ischemic stroke outcomes. By identifying risk factors, predicting the risk of poor prognosis and thus developing personalized treatment plans, it effectively reduces the probability of poor prognosis, leading to more effective secondary prevention. This review includes 41 studies since 2018 that used ML algorithms to build prognostic prediction models for ischemic stroke, transient ischemic attack (TIA), and acute ischemic stroke (AIS). We analyzed in detail the risk factors used in these studies, the sources and processing methods of the required data, the model building and validation, and their application in different prediction time windows. The results indicate that among the included studies, the top five risk factors in terms of frequency were cardiovascular diseases, age, sex, national institutes of health stroke scale (NIHSS) score, and diabetes. Furthermore, 64% of the studies used single-center data, 65% of studies using imbalanced data did not perform data balancing, 88% of the studies did not utilize external validation datasets for model validation, and 72% of the studies did not provide explanations for their models. Addressing these issues is crucial for enhancing the credibility and effectiveness of the research, consequently improving the development and implementation of secondary prevention measures.

[Urinary protein and renal pathological features in children with immunoglobulin A vasculitis with nephritis and hypercoagulability]. / 儿童IgAè¡€ç®¡ç‚Žè‚¾ç‚Žä¼´é«˜å‡çŠ¶æ€çš„å°¿è›‹ç™½å’Œè‚¾è„ç— ç†ç‰¹å¾åˆ†æž.

OBJECTIVES: To study the association of hypercoagulability with urinary protein and renal pathological damage in children with immunoglobulin A vasculitis with nephritis (IgAVN). METHODS: Based on the results of coagulation function, 349 children with IgAVN were divided into a hypercoagulability group consisting of 52 children and a non-hypercoagulability group consisting of 297 children. Urinary protein and renal pathological features were compared between the two groups, and the factors influencing the formation of hypercoagulability in children with IgAVN were analyzed. RESULTS: Compared with the non-hypercoagulability group, the hypercoagulability group had significantly higher levels of urinary erythrocyte count, 24-hour urinary protein, urinary protein/creatinine, urinary immunoglobulin G/creatinine, and urinary N-acetyl-ß-D-glucosaminidase (P<0.05). The hypercoagulability group also had a significantly higher proportion of children with a renal pathological grade of III-IV, diffuse mesangial proliferation, capillary endothelial cell proliferation, or >25% crescent formation (P<0.05). The multivariate logistic regression analysis showed that capillary endothelial cell proliferation and glomerular crescent formation >25% were associated with the formation of hypercoagulability in children with IgAVN (P<0.05). CONCLUSIONS: The renal injury in IgAVN children with hypercoagulability is more severe, with greater than 25% crescent formation and increased proliferation of glomerular endothelial cells being important contributing factors that exacerbate the hypercoagulable state in IgAVN.

Graphene Oxide-Intercalated Tetrazole-Based Coordination Polymers: Thermally Stable Hybrid Energetic Crystals with Enhanced Photosensitivity.

High-energy-density photosensitive pyrotechnics with good thermal stability have been in increasing demand in recent years. In this paper, graphene oxide (GO)-intercalated energetic coordination polymers (ECPs) are prepared with improved thermostability but great photosensitivity by using high nitrogen compounds azotetrazole (AT) and 5,5'-bistetrazole-1,1'-diolate dehydrate (BTO) as ligands. The decomposition activation energy (Ea) of Cu-AT has been increased from 135.7 to 151.9 kJ·mol-1 after intercalating 5 wt% GO, and in the meantime, the exothermic peak temperature (Tp) was increased by 12.6 °C. However, the decomposition Ea of Cu-BTO decreased under the effect of the same amount of GO with little effect on Tp. This confirms that GO has stabilization effects on the Cu-AT crystal, whereas the catalytic effects on Cu-BTO would dominate after dehydration with its crystal lattice collapse. Also, when the content of GO was 3%, the resultant GO0.03-Cu-AT exhibits a higher density (2.88 g·cm-3) and good thermostability (Tp = 293.7 °C). This ECP shows excellent low-energy laser ignition performance, which can be ignited with an energy of less than 1 mJ at a wavelength of 976 nm. Low-energy laser initiation is considered to be a safer but more reliable method than the traditional electrical-based ones.

Resveratrol-induced SIRT1 activation inhibits glycolysis-fueled angiogenesis under rheumatoid arthritis conditions independent of HIF-1α.

OBJECTIVE: This study investigated the impacts of SIRT1 activation on rheumatoid arthritis (RA)-related angiogenesis. METHODS: HUVECs were cultured by different human serum. Intracellular metabolites were quantified by UPLC-MS. Next, HUVECs and rat vascular epithelial cells under different inflammatory conditions were treated by a SIRT1 agonist resveratrol (RSV). Cytokines and biochemical indicators were detected by corresponding kits. Protein and mRNA expression levels were assessed by immunoblotting and PCR methods, respectively. Angiogenesis capabilities were evaluated by migration, wound-healing and tube-formation experiments. To down-regulate certain signals, gene-specific siRNA were applied. RESULTS: Metabolomics study revealed the accelerated glycolysis in RA serum-treated HUVECs. It led to ATP accumulation, but did not affect GTP levels. RSV inhibited pro-angiogenesis cytokines production and glycolysis in both the cells, and impaired the angiogenesis potentials. These effects were mimicked by an energy metabolism interrupter bikini in lipopolysaccharide (LPS)-primed HUVECs, largely independent of HIF-1α. Both RSV and bikinin can inhibit the activation of the GTP-dependent pathway Rho/ROCK and reduce VEGF production. Abrogation of RhoA signaling reinforced HIF-1α silencing-brought changes in LPS-stimulated HUVECs, and overshadowed the anti-angiogenesis potentials of RSV. CONCLUSION: Glycolysis provides additional energy to sustain Rho/ROCK activation in RA subjects, which promotes VEGF-driven angiogenesis and can be inhibited by SIRT1 activation.

Large common bile duct stones in high-risk elderly patients: Immediate endoscopic stone removal or elective stone removal? A single-center retrospective study.

BACKGROUND AND OBJECTIVE: For high-risk elderly patients with chronic diseases, endoscopic stone removal for large common bile duct stones is associated with a high risk of adverse events and incomplete stone removal. The aim of this study was to investigate whether the treatment strategy of short-term biliary plastic stent placement followed by elective endoscopic stone removal is more effective and safer than immediate endoscopic stone removal. METHODS: The data of 262 high-risk elderly patients who received endoscopic retrograde cholangiopancreatography (ERCP) for large common bile duct (CBD) stones from 2017 to 2022 were retrospectively analyzed. The patients were divided into group A (immediate stone removal) and group B (stent drainage + elective stone removal). The baseline data of the 2 groups were matched 1:1 by propensity score matching. The stone clearance rate, ERCP procedure time, total hospital stay, and procedure-related adverse events were compared between the matched groups. In group B, stone size before and after stent placement, hospital stay, procedure time and adverse events of two ERCPs were compared. RESULTS: A total of 57 pairs of patients were successfully matched between the 2 groups. The stone clearance rate in group B was higher than that in group A (89.5% vs. 75.3, P = 0.049). The total hospital stay in group B was longer than that in group A (11.86 ± 3.912 d vs. 19.14 ± 3.176 d, P<0.001). The total adverse event rate in group A was higher than that in group B (29.8% vs. 12.3%, P = 0.005). The incidence of cholangitis/cholecystitis after ERCP was significantly higher in group A than in group B (7.0% vs. 0.9% P = 0.029). There was no significant difference in the incidence of post-ERCP pancreatitis, bleeding, pneumonia, and cardio-cerebrovascular events between the 2 groups. There were no perforation cases in either group. After plastic biliary stent placement in group B, the stone size was significantly smaller than before stent placement (1.59 ± 0.544 cm vs. 1.95 ± 0.543 cm, P < 0.001), and there was no significant difference in the total adverse event incidence between the two ERCP procedures (18.8% vs. 10.9%, P = 0.214). CONCLUSION: For high-risk elderly patients with large CBD stones, the treatment strategy involving temporary placement of plastic stent and elective endoscopic stone removal is safer and more effective than immediate stone removal.

The electrostatic effect and its role in promoting electrocatalytic reactions by specifically adsorbed anions.

The adsorption of anions and its impact on electrocatalytic reactions are fundamental topics in electrocatalysis. Previous studies revealed that adsorbed anions display an overall poisoning effect in most cases. However, for a few reactions such as the hydrogen evolution reaction (HER), oxidation of small organic molecules (SOMs), and reduction of CO2 and O2, some specifically adsorbed anions can promote their reaction kinetics under certain conditions. The promotion effect is frequently attributed to the adsorbate induced modification of the nature of the active sites, the change of the adsorption configuration and free energy of the key reactive intermediate which consequently change the activation energy, the pre-exponential factor of the rate determining step etc. In this paper, we will give a mini review of the indispensable role of the classical double layer effect in enhancing the kinetics of electrocatalytic reactions by anion adsorption. The ubiquitous electrostatic interactions change both the potential distribution and the concentration distribution of ionic species across the electric double layer (EDL), which alters the electrochemical driving force and effective concentration of the reactants. The contribution to the overall kinetics is highlighted by taking HER, oxidation of SOMs, reduction of CO2 and O2, as examples.

Enzymes for microplastic-free agricultural soils.

Plastic mulch films and biofertilizers (processed sewage sludge, compost or manure) have helped to increase crop yields. However, there is increasing evidence that these practices significantly contribute to microplastic contamination in agricultural soils, affecting biodiversity and soil health. Here, we draw attention to the use of hydrolase enzymes that depolymerize polyester-based plastics as a bioremediation technique for agricultural soils (in situ), biofertilizers and irrigation water (ex situ), and discuss the need for fully biodegradable plastic mulches. We also highlight the need for ecotoxicological assessment of the proposed approach and its effects on different soil organisms. Enzymes should be optimized to work effectively and efficiently under the conditions found in natural soils (typically, moist solids at an ambient temperature with low salinity). Such optimization is also necessary to ensure that already distressed ecosystems are not disrupted any further.

Blue light stimulates light stress and phototactic behavior when received in the brain of Diaphorina citri.

Blue light with a wavelength of 400-470 nm is the composition of the visible light. However, in recent years, blue light contributed the most significance to light pollution due to the artificial light at night. Previously, we have demonstrated that the Asian citrus psyllid (ACP), Diaphorina citri, an important pest in citrus production, has significant positive phototaxis with a light-emitting diode light of 400 nm. In this study, ACP with positive phototactic behavior to 400 nm light (PH) and non-phototactic behavior to 400 nm light (NP) were collected, individually. Transcriptome dynamics of head tissues of PH and NP groups were captured by using RNA-sequencing technology, respectively. Forty-three to 46 million clean reads with high-quality values were obtained, and 1773 differential expressed genes (DEGs) were detected. Compared with the NP group, there were 841 up-regulated DEGs and 932 down-regulated DEGs in the PH group. Eight pathways were significantly enriched in the PH group in the KEGG database, while 43 up-regulated pathways and 25 down-regulated pathways were significantly enriched in the PH group in the GO database. The DGE approach was reliable validated by real time quantitative PCR. Results indicated that the blue light acted as an abiotic stress causing physiological and biochemical responses such as oxidative stress, protein denaturation, inflammation and tumor development in ACPs. Additionally, the light was absorbed by photoreceptors of ACPs, and converted into electrical signal to regulate neuromodulation. This study provides basic information for understanding the molecular mechanisms of ACP in response to blue light and provides a reference for further studies to elucidate phototactic behavior.

Machine learning model successfully identifies important clinical features for predicting outpatients with rotator cuff tears.

PURPOSE: The aim of this study is to develop a machine learning model to identify important clinical features related to rotator cuff tears (RCTs) using explainable artificial intelligence (XAI) for efficiently predicting outpatients with RCTs. METHODS: A retrospective review of a local clinical registry dataset was performed to include patients with shoulder pain and dysfunction who underwent questionnaires and physical examinations between 2019 and 2022. RCTs were diagnosed by shoulder arthroscopy. Six machine-learning algorithms (Stacking, Gradient Boosting Machine, Bagging, Random Forest, Extreme Gradient Boost (XGBoost), and Adaptive Boosting) were developed for the prediction. The performance of the models was assessed by the area under the receiver operating characteristic curve (AUC), Brier scores, and Decision curve. The interpretability of the predicted outcomes was evaluated using Shapley additive explanation (SHAP) values. RESULTS: A total of 1684 patients who completed questionnaires and clinical tests were included, and 417 patients with RCTs underwent shoulder arthroscopy. In six machining learning algorithms for predicting RCTs, the accuracy, AUC values, and Brier scores were in the range of 0.81-0.86, 0.75-0.92, and 0.15-0.19, respectively. The XGBoost model showed superior performance with accuracy, AUC, and Brier scores of 0.85(95% confidence interval, 0.82-0.87), 0.92 (95% confidence interval,0.90-0.94), and 0.15 (95% confidence interval,0.14-0.16), respectively. The Shapley plot showed the impact of the clinical features on predicting RCTs. The most important variables were Jobe test, Bear hug test, and age for prediction, with mean SHAP values of 1.458, 0.950, and 0.790, respectively. CONCLUSION: The machine learning model successfully identified important clinical variables for predicting patients with RCTs. In addition, the best algorithm was also integrated into a digital application to provide predictions in outpatient settings. This tool may assist patients in reducing their pain experience and providing prompt treatments. LEVEL OF EVIDENCE: Level III.

In Situ Observing and Tuning the Crystal Orientation of Two-Dimensional Layered Perovskite via the Chlorine Additive.

Precise control of crystal orientation in two-dimensional (2D) layered perovskites (LPs) is vital for their optoelectronic applications due to the structure-induced anisotropy in optical and electrical properties. Herein, we directly observe and control the crystal orientation of the butylammonium-based 2D LP films. Employing the synchrotron-based in situ grazing-incidence X-ray diffraction technique, we reveal the orientation modulation mechanism of the Cl additive by following the crystallization dynamics and chemical conversion pathways during film formation. Two new Cl-related intermediates are identified which serve as templates directing the orientational growth of the 2D LP films. We fine-tune the crystal orientation of 2D LP films through the Cl additive and incorporate the films with the requisite crystal orientations in solar cells and photodetectors. The optoelectronic performances of the devices show a strong correlation with the crystal orientation of the 2D LP films.

Discovery of pyrazole-carbohydrazide with indole moiety as tubulin polymerization inhibitors and anti-tumor candidates.

In this work, a series of indole-containing pyrazole-carbohydrazide derivatives A1-A25 were synthesized, and their biological activity on tubulin polymerization inhibition and mitotic catastrophe was evaluated. For introducing indole group to CA-4 pattern, the carbohydrazide linker was used for the first time. As the top hit, A18 suggested notable antiproliferation efficacy and tubulin polymerization inhibitory activity. Inferring comparable antitubulin effect with the positive control Colchicine, A18 indicated obviously lower cyto-toxicity. The cell scratch test showed that A18 could block the cell migration, while the confocal imaging depicted that A18 could induce the mitotic catastrophe via a Colchicine-like approach. The docking simulation visualized the probable binding pattern of A18. With the information in this work, some new hints on modification might be involved in further tubulin-related investigations.