[Chemical constituents and their α-glucosidase inhibitory activities of seeds of Moringa oleifera].

The chemical constituents of the seeds of Moringa oleifera were isolated and purified by using Sephadex LH-20, Toyo-pearl HW-40F, silica gel, ODS, and MCI column chromatography. The structures of compounds were identified by high-resolution mass spectrometry, ~1H-NMR, ~(13)C-NMR, HMQC, HMBC, and ~1H-~1H COSY, as well as physicochemical properties of compounds and literature data. Twelve compounds were isolated from 30% ethanol fraction of the seeds of M. oleifera and identified as ethyl-4-O-α-L-rhamnosyl-α-L-rhamnoside(1), ethyl-3-O-α-L-rhamnosyl-α-L-rhamnoside(2),(4-hydroxybenzyl)ethyl carbamate(3),(4-aminophenyl)acetic acid(4), ethyl-α-L-rhamnoside(5), methyl-α-L-rhamnoside(6), moringapyranosyl(7), 2-[4-(α-L-rhamnosyl)phenyl]methyl acetate(8), niaziridin(9), 5-hydroxymethyl furfural(10), 4-hydroxybenzeneacetamide(11), and 4-hydroxybenzoic acid(12). Among them, compounds 1 and 2 are two new compounds, compound 3 is a new natural product, and compounds 4-5 were yielded from Moringa plant for the first time. All compounds were evaluated for α-glucosidase inhibitory activity in vitro. Compound 10 showed excellent inhibitory activity with IC_(50) of 210 µg·mL~(-1).

MAVI1, an endoplasmic reticulum-localized microprotein, suppresses antiviral innate immune response by targeting MAVS on mitochondrion.

Pattern recognition receptor-mediated innate immunity is critical for host defense against viruses. A growing number of coding and noncoding genes are found to encode microproteins. However, the landscape and functions of microproteins in responsive to virus infection remain uncharacterized. Here, we systematically identified microproteins that are responsive to vesicular stomatitis virus infection. A conserved and endoplasmic reticulum-localized membrane microprotein, MAVI1 (microprotein in antiviral immunity 1), was found to interact with mitochondrion-localized MAVS protein and inhibit MAVS aggregation and type I interferon signaling activation. The importance of MAVI1 was highlighted that viral infection was attenuated and survival rate was increased in Mavi1-knockout mice. A peptide inhibitor targeting the interaction between MAVI1 and MAVS activated the type I interferon signaling to defend viral infection. Our findings uncovered that microproteins play critical roles in regulating antiviral innate immune responses, and targeting microproteins might represent a therapeutic avenue for treating viral infection.

Six New Phenolic Glycosides from the Seeds of Moringa oleifera Lam. and Their α-Glucosidase Inhibitory Activity.

Plant-derived phytochemicals have recently drawn interest in the prevention and treatment of diabetes mellitus (DM). The seeds of Moringa oleifera Lam. are widely used in food and herbal medicine for their health-promoting properties against various diseases, including DM, but many of their effective constituents are still unknown. In this study, 6 new phenolic glycosides, moringaside B-G (1-6), together with 10 known phenolic glycosides (7-16) were isolated from M. oleifera seeds. The structures were elucidated by 1D and 2D NMR spectroscopy and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data analysis. The absolute configurations of compounds 2 and 3 were determined by electronic circular dichroism (ECD) calculations. Compounds 2 and 3 especially are combined with a 1,3-dioxocyclopentane moiety at the rhamnose group, which are rarely reported in phenolic glycoside backbones. A biosynthetic pathway of 2 and 3 was assumed. Moreover, all the isolated compounds were evaluated for their inhibitory activities against α-glucosidase. Compounds 4 and 16 exhibited marked activities with IC50 values of 382.8 ± 1.42 and 301.4 ± 6.22 µM, and the acarbose was the positive control with an IC50 value of 324.1 ± 4.99 µM. Compound 16 revealed better activity than acarbose.

Construction and application of an applicability evaluation system for garlic planters based on fuzzy comprehensive evaluation.

The widespread use of garlic planters has been hampered by the lack of comprehensive applicability evaluation criteria, as their functional and structural designs are sometimes subpar and their purchase and use are not always financially advantageous. In order to close this gap in the applicability evaluation system for garlic planters, a three-level index system based on Technical indicators, Economic indicators, and Working condition indicators was proposed in the current study. A fuzzy comprehensive evaluation method was then applied to achieve the evaluation with the help of an analytical hierarchy process and validity test. By providing basic descriptions, physical test results and specific calculation results to the consulted ten experts and collecting the scores for the 3rd level indicators, the first-generation garlic planter was analyzed for the practical application of the Pizhou-white garlic planting area based on the established applicability evaluation system. The evaluated score of 74.47 was towards the bottom of the "good" range. The findings also suggest that enhancing operational safety, implementing plant spacing and planting depth adjustments, enhancing ease of operation, and to some extent lowering capital cost will improve functional performance and economic performance. The upgraded machine was subsequently created using the optimization guidelines. Its applicability score was 77.52, representing a 4.1% gain over the original computer. It has reached the midpoint of the "good" range and has achieved the optimization goal. The proposed applicability evaluation system can generally draw unbiased conclusions and provide scientific evaluation methods for the promotion of garlic planters in specific areas, benefiting not only the design and improvement of garlic planters but also the purchasing and application of them. However, further indicator refinement and a more thorough evaluation method appear necessary before the evaluation system is made more widely available.

Severe major vessel injury during peadicle screw removal: a case report.

Introduction: Pedicle screw fixation (PSF) has been the standard therapy for the treatment of various spinal diseases. Although complications are identified regularly, iatrogenic vascular injury is one of the rare but life-threatening complications. In this literature, we describe the first case of inferior vena cava (IVC) injury during pedicle screw removal. Case description: A 31-year-old man was treated by percutaneous pedicle screw fixation for an L1 compression fracture. After a year, the fracture healed well and hardware removal surgery was performed. During the procedure, the hardware on the right was removed unremarkably except for the L2 pedicle screw which slipped into the retroperitoneum because of the improper technique. The CT angiogram revealed the screw had breached the anterior cortex of the L2 vertebral body and penetrated the IVC. After multidisciplinary cooperation, the defect of IVC was reconstructed and the L2 screw was removed from the posterior approach in the end. Result: The patient recovered well and was discharged after 3 weeks without further events. The removal of the contralateral implants was unremarkable at 7 months postoperatively. At the 3-year follow-up, the patient returned to his normal daily activity without any complaints. Conclusion: Although pedicle screw removal is a rather simple procedure, severe complications may have occurred from this procedure. Surgeons should keep vigilant to avoid the complication noted in this case.

Degradation of Aflatoxin B1 in Peanut Oil by Ultraviolet-LED Cold-Light Irradiation and Structure Elucidation of the Degradation Products.

This study aimed to determine the efficiency of ultraviolet (UV)-LED cold light treatment on the degradation of aflatoxin (AF)B1 in peanut oils. The peanut oil samples obtained from different places in China and abroad were determined for AFB1 degradation efficiency of the UV-LED cold-light irradiation method. The degradation products were analyzed by ultra-high performance liquid chromatography coupled to quadrupole orbitrap high-resolution mass spectrometry (UPLC-Q-Exactive MS). The results indicated that the AFB1 content in all peanut oil samples decreased rapidly after 5 min of irradiation. Four main photodegradation products (C18H16O7, C17H14O7, C17H14O7, and C17H14O8) were identified using the established LC-MS method. Their chemical structures were postulated based on the LC-MS data. Also, the degradation pathways were proposed based on the data obtained. Oxidation and reduction reactions were mainly responsible for AFB1-decomposition. The reactions occurred at the furan and lactone rings. These findings demonstrated that UV-LED cold-light irradiation was an effective method for treating AFB1- contaminated peanut oil.

The Cut-Off Value of Serum Anti-Müllerian Hormone Levels for the Diagnosis of Turner Syndrome with Spontaneous Puberty.

Objective: Preservation of fertility in Turner syndrome (TS) patients may be feasible through cryopreservation of ovarian tissue before follicles begin to disappear. Anti-Müllerian hormone (AMH) is said to be a predictive factor of spontaneous pubertal development in TS. We aimed to determine the cut-off values of AMH for the diagnosis of TS girls with spontaneous puberty. Design and methods: A total of 95 TS patients between 4 and 17 years were evaluated at the Department of Pediatric Genetic Metabolism and Endocrinology from July 2017 to March 2022. Serum AMH, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were analyzed according to age, karyotype, pubertal development, and ultrasound ovarian visualization. Receiver-operating characteristic (ROC) curve analyzes were used to test the utility of AMH for the diagnosis of TS girls with spontaneous puberty. Results: One-fourth of TS girls aged 8-17 years had spontaneous breast development, with the ratios as follows: 45, X (6/28, 21.4%), mosaicism (7/12, 58.3%), and mosaicism with structural X chromosome abnormalities (SCA) (2/13, 15.4%), SCA (1/13, 7.7%), and Y chromosome (1/3, 33.3%). The AMH cut-off value for the prediction of spontaneous puberty in TS patients was 0.07 ng/ml, with sensitivity and specificity both at 88%. FSH, LH levels, and Karyotypes could not be considered as markers of spontaneous puberty in TS (P > 0.05). A strong relationship was observed between serum AMH levels and spontaneous puberty or ultrasound bilateral ovarian visualization. Conclusions: The AMH cut-off value for the prediction of spontaneous puberty in TS girls aged 8-17 years was 0.07 ng/ml, with sensitivity and specificity both at 88%. However, spontaneous puberty in these patients is not predictable based on karyotype or FSH or LH levels.

Using image-based machine learning and numerical simulation to predict pesticide inline mixing uniformity.

BACKGROUND: Accurate pesticide inline mixing uniformity (PIMU) evaluation for direct nozzle injection systems (DNIS) helps evaluate system performance and develop efficient inline mixers. Based on supervised machine learning (ML), inline mixing images and computational fluid dynamics (CFD) simulations are directly associated for realizing intelligent PIMU predictions. RESULTS: Image sets can be reduced to less than 3% of the data size at the same time as retaining 98% of information using principal component analysis (PCA). The CFD results, as referenced values for ML, were justified by mixture sampling experiments. Enhanced images for the long-mixing tube effectively trained models including generalized linear model (GLM), support vector regression (SVR), BP-neural network (NNW), and classification and regression trees (CART). By testing the re-collected images, the verification accuracy of GLM was less than 95% and it failed to recognize uniformity differences under varying working conditions, whereas NNW, CART and SVR realized it with an accuracy for NNW and CART higher than 97% and for SVR slightly lower than 97%. By testing images of the jet mixer, the prediction accuracy compared with the CFD results of NNW and CART was also higher than 97%, although that for SVR was relatively lower, and insignificant declines in accuracy were observed on comparing the results with mixture sampling experiments. CONCLUSION: PCA facilitates evaluations of CFD-referenced PIMU using image-based ML. Models trained by enhanced image sets of the long-mixing tube have satisfactory performance. NNW and CART performed slightly better than SVR, and they can be used as tools to improve the rationality when evaluating PIMU in DNIS. © 2022 Society of Chemical Industry.

Transcriptome analysis reveals the roles of phytohormone signaling in tea plant (Camellia sinensis L.) flower development.

BACKGROUND: Tea plant (Camellia sinensis (L.) O. Kuntze) is an important economic tea crop, but flowering will consume a lot of nutrients of C. sinensis, which will seriously affect the nutritional growth of C. sinensis. However, there are few studies on the development mechanism of C. sinensis flower, and most studies focus on a single C. sinensis cultivar. RESULTS: Here, we identified a 92-genes' C. sinensis flower development core transcriptome from the transcriptome of three C. sinensis cultivars ('BaiYe1', 'HuangJinYa' and 'SuChaZao') in three developmental stages (bud stage, white bud stage and blooming stage). In addition, we also reveal the changes in endogenous hormone contents and the expression of genes related to synthesis and signal transduction during the development of C. sinensis flower. The results showed that most genes of the core transcriptome were involved in circadian rhythm and autonomous pathways. Moreover, there were only a few flowering time integrators, only 1 HD3A, 1 SOC1 and 1 LFY, and SOC1 played a dominant role in the development of C. sinensis flower. Furthermore, we screened out 217 differentially expressed genes related to plant hormone synthesis and 199 differentially expressed genes related to plant hormone signal transduction in C. sinensis flower development stage. CONCLUSIONS: By constructing a complex hormone regulation network of C. sinensis flowering, we speculate that MYC, FT, SOC1 and LFY play key roles in the process of endogenous hormones regulating C. sinensis flowering development. The results of this study can a provide reference for the further study of C. sinensis flowering mechanism.

SLC26A4 Mutation Promotes Cell Apoptosis by Inducing Pendrin Transfer, Reducing Cl- Transport, and Inhibiting PI3K/Akt/mTOR Pathway.

Objective: Pendrin is encoded by SLC26A4, which is expressed in the apical membrane of inner ear epithelial cells and drives chloride reabsorption in the apical septum. In the inner ear, pendrin dysfunction and hypofunctional mutations lead to vestibular aqueduct (EVA) enlargement and sensory neural hearing loss. Mutations in SLC26A4 are a common reason of deafness. However, the underlying mechanisms of SLC26A4 mutants in hearing loss remain unknown. Methods: In the present study, pEGFP-N1 carrying wild-type and mutant SLC26A4 (c.85G>A, c.2006A>T, and c.853G>A) were transfected into HEK-293T cells. GFP fluorescence and GFP levels were determined. SLC26A4 mRNA levels were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Then, the expression of chloride intracellular channel 1 (CLIC1) and CLIC2 was measured by Immunofluorescence assay. Intracellular chloride concentration and apoptotic rate were analyzed by flow cytometry. The levels of membrane/cytoplasmic pendrin, apoptosis-associated proteins, and the PI3K/Akt/mTOR pathway members were determined by Western blot. Results: Constructed SLC26A4 mutant 1 (c.85G>A), SLC26A4 mutant 2 (c.2006A>T), and SLC26A4 mutant 3 (c.853G>A). The wild-type and 3 mutations were stably expressed in HEK-293T. SLC26A4 mRNA expression was significantly increased after transfection with wild-type SLC26A4 and mutant SLC26A4 compared with the untransfected vector group (P < 0.01). Compared with the vector group, the expression levels of membrane pendrin, cytoplasmic pendrin, CLIC1, CLIC2, Bcl-2, p-PI3K, p-Akt, and p-mTOR were upregulated. Compared with the vector group, the chloride concentration, cell apoptotic rate, and the expression levels of caspase-3, caspase-9, and Bax were downregulated. Compared with the vector group, the above effects of SLC26A4 were reversed after the SLC26A4 mutant. Conclusion: After SLC26A4 mutation, pendrin was transferred from the membrane, the chloride intracellular channel function was reduced, and the excessive accumulation of chloride in the cytoplasm induced cell apoptosis by inhibited PI3K/Akt/mTOR pathway phosphorylation.

The Improvement Path for Regionally Coordinated Green Development: Evidence from Social Network Analysis.

Regionally coordinated green development has been widely documented in China. However, most previous studies have investigated it from the perspective of linearity, while the spatial correlation of green development is nonlinear. Based on 48 cities in Bohai Rim, this study used a social network analysis to measure the spatial network, with an emphasis on the internal structure of regional green development, and analyzed the driving factors of regionally coordinated green development from the perspective of nonlinearity. We found that large cities have formed a "siphon effect" and that the polarization of eco-efficiency has become increasingly serious. There are limited connections, some of which are redundant, in the spatial network of green development, while the stability of the network is strong. Additionally, reducing the differences in environmental regulation approaches among cities can have a positive impact on the spatial correlation and spillover effect of green development, thereby promoting regionally coordinated green development among cities in the Bohai Rim.

Acute Effects of Different Warm-up Protocols on Sports Performance in Elite Male Collegiate Handball Players.

ABSTRACT: Chen, CH, Chang, CK, Tseng, WC, Chiu, CH, Dai, X, and Ye, X. Acute effects of different warm-up protocols on sports performance in elite male collegiate handball players. J Strength Cond Res 36(8): 2262-2267, 2022-This study aimed to examine the effects of 3 different warm-up protocols on subsequent sports performance in elite male collegiate handball players. Fifteen handball players (19.0 ± 2.4 years) completed 3 separated randomly sequenced experimental visits. During each visit, they started with different warm-up protocols (traditional warm-up [TRAD] vs. warm-up with core stability exercises [CORE] vs. warm-up with elastic band exercises [ELAS]) and completed with a series of randomly ordered sport-specific performance testing measurements: 30-m sprint, countermovement jump, medicine ball overhead forward throw, and standing and jump handball throw tests. Both CORE and ELAS protocols induced statistically significant differences (p < 0.05) on overall sports performance (sprint time, jump height, medicine ball throwing peak velocity and power, and handball throwing velocities), as compared to the TRAD. In addition, the ELAS protocol imposed small-to-medium effects (effect size range: 0.45-0.82), enhancing handball throwing velocity and medicine ball throwing performance comparing with the CORE. Sport-specific warm-up protocols that contain core stability or elastic band-based exercises likely induced subsequent performance enhancements (sprint, jump, and throw) in elite male collegiate handball players when compared with TRAD. Furthermore, including elastic band exercises in the warm-up protocol even induced superior upper-body performance enhancement (explosive power and handball throwing velocity) than other protocols. Therefore, preconditioning warm-up activities using elastic band-based exercises can be integrated into a traditional sport-specific warm-up protocol for elite collegiate handball players before competition or training.

Could Metabolic Syndrome Be a Predictor of Survival Outcomes in Upper Tract Urothelial Carcinoma? A Propensity Score Matching Study in a Large Chinese Center.

Purpose: To evaluate the prognostic value of metabolic syndrome (MetS) in upper tract urothelial carcinoma (UTUC) patients based on propensity score matching (PSM) analysis. Patients and Methods: A total of 573 patients with UTUC after radical nephroureterectomy were included at Peking University People's Hospital from January 2007 to April 2021. MetS was diagnosed according to the criteria of Chinese Diabetes Society and was defined as the presence of 3 or more of the following 4 conditions (obesity, hyperglycemia, hypertension, high triglycerides and/or low high-density lipoprotein-cholesterol). Patients were divided into two groups based on whether they had MetS, whose variables were adjusted using 1:1 PSM analysis with a caliber of 0.02 to minimize selection bias. Univariate and multivariate Cox regression analysis were used to evaluate the association of MetS and its components with pathological outcomes after adjusting preoperative confounders by propensity score matching. The Kaplan-Meier method was used to estimate overall survival (OS), cancer-specific survival (CSS), and intravesical recurrence-free survival (IVRFS) after surgery. Results: MetS was significantly correlated with older age, a history of coronary heart disease, high Charlson Comorbidity Index, low estimated Glomerular filtration rate, and low aspartate/alanine aminotransferase ratio (all P<0.05). Multivariate Cox regression analysis and Kaplan-Meier curves demonstrated that MetS showed no statistical correlation with lower OS or IVRFS and approaching significance with lower CSS (P=0.063) before PSM. After PSM, the 5-year OS, CSS, and IVRFS were 64.1%, 74.7%, and 77.2%, respectively, in the MetS group, compared with 67.4%, 78.8%, and 77.2%, respectively, in non-MetS group. Univariate Cox regression analyses showed that MetS and its components were not associated with decreased OS, CSS, or IVRFS (all P>0.05). Conclusion: In our study, no statistical difference was found between MetS and survival outcomes in UTUC, except a marginal association with lower CSS. Further studies are needed to evaluate the role of MetS and its each single component on UTUC.

Anfibatide alleviates inflammation and apoptosis via inhibiting NF-kappaB/NLRP3 axis in ischemic stroke.

Recent evidence suggests that Nod-like receptor protein-3 (NLRP3) inflammasome is a key mediator of inflammatory response and can induce the activation of apoptosis signaling pathways in ischemic stroke. In this research, we assessed the effects of anfibatide (ANF) on inflammatory and apoptosis in cerebral ischemic injury and the potential mechanisms. Middle cerebral artery occlusion (MCAO) model was established on male Sprague-Dawley rats to induce cerebral ischemia/reperfusion (I/R) injury in vivo. Primary cortical neurons (PCN) cells were exposed to oxygen-glucose deprivation and reintroduction (OGD/R) to mimic cerebral I/R injury in vitro. The results showed that ANF markedly alleviated infarct volume, neurological deficit and neurobehavioral impairment in MCAO/R rats, enhanced cell viability and decreased LDH release in PCN after OGD/R. The number of TUNEL-positive cells, Bax, cleaved-caspase-3, p-IκBα, p-p65, NLRP3, ASC, cleaved caspase-1, IL-ß and IL-18 proteins expression were significantly upregulated in the cortex of MCAO/R rats and PCN exposed to OGD/R, NLRP3 and caspase-1 mRNA levels were also evidently elevated. Bcl-2 protein expression significantly decreased in the cortex of MCAO/R rats. Treatment with ANF obviously inhibited the expression of p-IκBα, p-p65, NLRP3, ASC, cleaved caspase-1, Bax and cleaved-caspase-3, promoted the expression of Bcl-2, then decreased the TUNEL-positive cell number and the level of inflammatory cytokines (IL-ß and IL-18) in cerebral ischemia reperfusion in vito and in vitro. Our findings suggest that ANF exerts effects of alleviating inflammation and apoptosis through inhibiting NF-kappaB/NLRP3 axis. ANF is a potential candidate for treating cerebral I/R injury.

Quantitative Jones matrix imaging using vectorial Fourier ptychography.

This paper presents a microscopic imaging technique that uses variable-angle illumination to recover the complex polarimetric properties of a specimen at high resolution and over a large field-of-view. The approach extends Fourier ptychography, which is a synthetic aperture-based imaging approach to improve resolution with phaseless measurements, to additionally account for the vectorial nature of light. After images are acquired using a standard microscope outfitted with an LED illumination array and two polarizers, our vectorial Fourier ptychography (vFP) algorithm solves for the complex 2x2 Jones matrix of the anisotropic specimen of interest at each resolved spatial location. We introduce a new sequential Gauss-Newton-based solver that additionally jointly estimates and removes polarization-dependent imaging system aberrations. We demonstrate effective vFP performance by generating large-area (29 mm2), high-resolution (1.24 µm full-pitch) reconstructions of sample absorption, phase, orientation, diattenuation, and retardance for a variety of calibration samples and biological specimens.

Strontium Ion Removal From Artificial Seawater Using a Combination of Adsorption With Biochar and Precipitation by Blowing CO2 Nanobubble With Neutralization.

While enjoying the convenience of nuclear energy development, the environmental contamination by radionuclide leakage is of significant concern. Because of its cost-effectiveness and environmental friendliness, biochar has attracted a lot of attention in the field of radioactive water treatment. Herein, a novel teak peel modified biochar (labeled as PMBN3) was prepared and applied to remove strontium from artificial seawater. The characterisation of the prepared PMBN3 showed it contains numerous oxygen-containing functional groups (i.e. carboxyl and hydroxyl groups), laminar morphology, mesoporous structure, large specific surface area. PMBN3 exhibited great advantages in Sr(II) adsorption, such as rapid adsorption kinetics (<1 h for equilibrium) and superior reusability. The adsorption of strontium by biochar is consistent with pseudo-second order and internal diffusion kinetic models. Among the four types of adsorption isotherms, the Freundlich isotherm showed the best fit with R2 > 0.98. The calculated thermodynamic parameters indicate that strontium adsorption on biochar occurs exothermically and spontaneously. Furthermore, for efficient removal of Sr(II), CO2 nanobubbles were blown into artificial seawater to precipitate the interfering metal ions, and followed by the adsorption of PMBN3 towards residual metal ions with the removal rate of Sr(II) over 99.7%. Finally, mechanistic studies have shown that the strontium adsorption process by PMBN3 is a multiple adsorption mechanism consisting of ion exchange between H+ (from -OH and -COOH) and Sr(II), and weak intermolecular forces between Sr(II) and the PMBN3 adsorbent. This study creatively combines chemisorption and nanobubble precipitation for strontium removal, which provides great reference value and guidance for environmental remediation.

Induction chemotherapy with albumin-bound paclitaxel plus lobaplatin followed by concurrent radiochemotherapy for locally advanced esophageal cancer.

BACKGROUND: Albumin-bound paclitaxel (ABP) has been used as second- and higher-line treatments for advanced esophageal cancer, and its efficacy and safety have been well demonstrated. Lobaplatin (LBP) is a third-generation platinum antitumor agent; compared with the first two generations of platinum agents, it has lower toxicity and has been approved for the treatment of breast cancer, small cell lung cancer, and chronic granulocytic leukemia. However, its role in the treatment of esophageal cancer warrants further investigations. AIM: To investigate the efficacy and safety of induction chemotherapy with ABP plus LBP followed by concurrent radiochemotherapy (RCT) for locally advanced esophageal cancer. METHODS: Patients with pathologically confirmed advanced esophageal squamous cell carcinoma (ESCC) at our hospital were enrolled in this study. All patients were treated with two cycles of induction chemotherapy with ABP plus LBP followed by concurrent RCT: ABP 250 mg/m2, ivgtt, 30 min, d1, every 3 wk; and LBP, 30 mg/m2, ivgtt, 2 h, d1, every 3 wk. A total of four cycles were scheduled. The dose of the concurrent radiotherapy was 56-60 Gy/28-30 fractions, 1.8-2.0 Gy/fraction, and 5 fractions/wk. RESULTS: A total of 29 patients were included, and 26 of them completed the treatment protocol. After the induction chemotherapy, the objective response rate (ORR) was 61.54%, the disease control rate (DCR) was 88.46%, and the progressive disease (PD) rate was 11.54%; after the concurrent RCT, the ORR was 76.92%, the DCR was 88.46%, and the PD rate was 11.54%. The median progression-free survival was 11.1 mo and the median overall survival was 15.83 mo. Cox multivariate analysis revealed that two cycles of induction chemotherapy followed by concurrent RCT significantly reduced the risk of PD compared with two cycles of chemotherapy alone (P = 0.0024). Non-hematologic toxicities were tolerable, and the only grade 3 non-hematologic toxicity was radiation-induced esophagitis (13.79%). The main hematologic toxicity was neutropenia, and no grade 4 adverse event occurred. CONCLUSION: Induction chemotherapy with ABP plus LBP followed by concurrent RCT is effective in patients with locally advanced ESCC, with mild adverse effects. Thus, this protocol is worthy of clinical promotion and application.

SOD2 Alleviates Hearing Loss Induced by Noise and Kanamycin in Mitochondrial DNA4834-deficient Rats by Regulating PI3K/MAPK Signaling.

Superoxide dismutase 2 (SOD2)-mediated gene therapy has significant protective effects against kanamycin-induced hearing loss and hair cell loss in the inner ear, but the underlying mechanisms are still unclear. Herein, an in vivo aging model of mitochondrial DNA (mtDNA)4834 deletion mutation was established using D-galactose, and the effects of noise or kanamycin on inner ear injury was investigated. Rats subjected to mtDNA4834 mutation via D-galactose administration showed hearing loss characterized by the disruption of inner ear structure (abnormal cell morphology, hair cell lysis, and the absence of the organ of Corti), increased SOD2 promoter methylation, and an increase in the degree of apoptosis. Exposure to noise or kanamycin further contributed to the effects of D-galactose. SOD2 overexpression induced by viral injection accordingly counteracted the effects of noise and kanamycin and ameliorated the symptoms of hearing loss, suggesting the critical involvement of SOD2 in preventing deafness and hearing-related conditions. The PI3K and MAPK signaling pathways were also regulated by noise/kanamycin exposure and/or SOD2 overexpression, indicating that they may be involved in the therapeutic effect of SOD2 against age-related hearing loss.

Correction: Extracting Family History Information From Electronic Health Records: Natural Language Processing Analysis.

[This corrects the article DOI: 10.2196/24020.].

Extracting Family History Information From Electronic Health Records: Natural Language Processing Analysis.

BACKGROUND: The prognosis, diagnosis, and treatment of many genetic disorders and familial diseases significantly improve if the family history (FH) of a patient is known. Such information is often written in the free text of clinical notes. OBJECTIVE: The aim of this study is to develop automated methods that enable access to FH data through natural language processing. METHODS: We performed information extraction by using transformers to extract disease mentions from notes. We also experimented with rule-based methods for extracting family member (FM) information from text and coreference resolution techniques. We evaluated different transfer learning strategies to improve the annotation of diseases. We provided a thorough error analysis of the contributing factors that affect such information extraction systems. RESULTS: Our experiments showed that the combination of domain-adaptive pretraining and intermediate-task pretraining achieved an F1 score of 81.63% for the extraction of diseases and FMs from notes when it was tested on a public shared task data set from the National Natural Language Processing Clinical Challenges (N2C2), providing a statistically significant improvement over the baseline (P<.001). In comparison, in the 2019 N2C2/Open Health Natural Language Processing Shared Task, the median F1 score of all 17 participating teams was 76.59%. CONCLUSIONS: Our approach, which leverages a state-of-the-art named entity recognition model for disease mention detection coupled with a hybrid method for FM mention detection, achieved an effectiveness that was close to that of the top 3 systems participating in the 2019 N2C2 FH extraction challenge, with only the top system convincingly outperforming our approach in terms of precision.