HELM-GPT: de novo macrocyclic peptide design using generative pre-trained transformer.

MOTIVATION: Macrocyclic peptides hold great promise as therapeutics targeting intracellular proteins. This stems from their remarkable ability to bind flat protein surfaces with high affinity and specificity while potentially traversing the cell membrane. Research has already explored their use in developing inhibitors for intracellular proteins, such as KRAS, a well-known driver in various cancers. However, computational approaches for de novo macrocyclic peptide design remain largely unexplored. RESULTS: Here, we introduce HELM-GPT, a novel method that combines the strength of the hierarchical editing language for macromolecules (HELM) representation and generative pre-trained transformer (GPT) for de novo macrocyclic peptide design. Through reinforcement learning (RL), our experiments demonstrate that HELM-GPT has the ability to generate valid macrocyclic peptides and optimize their properties. Furthermore, we introduce a contrastive preference loss during the RL process, further enhanced the optimization performance. Finally, to co-optimize peptide permeability and KRAS binding affinity, we propose a step-by-step optimization strategy, demonstrating its effectiveness in generating molecules fulfilling both criteria. In conclusion, the HELM-GPT method can be used to identify novel macrocyclic peptides to target intracellular proteins. AVAILABILITY AND IMPLEMENTATION: The code and data of HELM-GPT are freely available on GitHub (https://github.com/charlesxu90/helm-gpt).

Evaluating the necessity of lymph node sampling in lung adenocarcinoma with ground glass opacities.

BACKGROUND: Ground glass opacity is observed frequently in the early stages of lung adenocarcinoma and is associated with a favorable prognosis and a low incidence of lymph node metastasis. However, the necessity of lymph node sampling in these patients is questionable, although current guidelines still recommend it. METHODS: Radiologic and clinical data were retrospectively collected and analyzed for 2,298 patients with lung cancer who underwent surgical resection for lesions ≤15 mm during 2022. Based on the consolidation tumor ratios, patients were categorized into 4 groups (pure ground glass opacity, ground glass opacity-predominant, solid-predominant, and pure solid). The incidence of lymph node metastasis in each group was examined. RESULTS: A total of 2,298 patients with a median age of 54.0 years were enrolled in this study. Tumors were categorized into 4 types: 1,427 (62.1%) were pure ground glass opacity, which constituted the majority, while 421 (18.3%) were ground glass opacity-predominant, 330 (14.4%) were solid-predominant, and the remaining 120 (5.2%) were pure solid. Significant positive correlations were revealed between the consolidation tumor ratio group and pathologic grade (P < .001, ρ = 0.307), T stage (P < .001, ρ = 0.270), and N stage (P < .001, ρ = 0.105). Among the included cases, only 7 cases with metastasis were in the pure solid group. Within this group, 113 cases (94.2%) were N0, 5 cases (4.2%) were N1, and 2 cases (1.7%) were N2. CONCLUSION: Lymph node metastasis exclusively occurred in the pure solid group, suggesting that for nodules <15 mm, lymph node sampling may be crucial for pure solid nodules but less so for those containing ground glass opacities.

The role of immune cell signatures in the pathogenesis of ovarian-related diseases: a causal inference based on mendelian randomization.

BACKGROUND: Immune cells play a pivotal role in maintaining ovarian function. However, the specific contributions of different immune cell phenotypes to the pathogenesis of specific ovarian-related diseases remain poorly understood. We aim to investigate the correlation between 731 immunophenotypes and ovarian-related diseases. MATERIALS AND METHODS: Utilizing publicly available genetic data, we undertook a series of quality control measures to identify instrumental variables (IVs) associated with exposure. Subsequently, we conducted two-sample Mendelian randomization (MR) using inverse variance weighting to explore the causal relationships between 731 immune cell features and six ovarian-related diseases: ovarian cysts, ovarian dysfunction, premature ovarian failure (POF), polycystic ovary syndrome (PCOS), benign neoplasm of ovary, and malignant neoplasm of ovary at the genetic level. Sensitivity analyses, including leave-one-out and other MR analysis models, were performed. Finally, Bayesian colocalization (COLOC) analysis was employed to identify specific co-localized genes, thereby validating the MR results. RESULTS: At the significance level corrected by Bonferroni, four immune phenotypes, including CD25 on IgD- CD38- B cells, were associated with ovarian cysts; four immune phenotypes, including CD39+ CD4+ T cell Absolute Count, were associated with ovarian dysfunction; eight immune phenotypes, including SSC-A on HLA DR+ CD8+ T cells, were associated with POF; five immune phenotypes, including CD20- CD38- B cell Absolute Count, were associated with PCOS; five immune phenotypes, including CD4+ CD8dim T cell Absolute Count, were associated with benign ovarian tumors; and three immune phenotypes, including BAFF-R on IgD- CD38+ B cells, were associated with malignant ovarian tumors. Sensitivity analysis indicated robust results. COLOC analysis identified four immune cell co-localized variants (rs150386792, rs117936291, rs75926368, rs575687159) with ovarian diseases. CONCLUSION: Our study elucidates the close genetic associations between immune cells and six ovarian-related diseases, thereby providing valuable insights for future research endeavors and clinical applications.

Nucleic Acid Sensing by STING Induces an IFN-like Antiviral Response in a Marine Invertebrate.

The cytosolic detection of pathogen-derived nucleic acids has evolved as an essential strategy for host innate immune defense in mammals. One crucial component in this process is the stimulator of IFN genes (STING), which acts as a vital signaling adaptor, connecting the cytosolic detection of DNA by cyclic GMP-AMP (cGAMP) synthase (cGAS) to the downstream type I IFN signaling pathway. However, this process remains elusive in invertebrates. In this study, we present evidence demonstrating that STING, an ortholog found in a marine invertebrate (shrimp) called Litopenaeus vannamei, can directly detect DNA and initiate an IFN-like antiviral response. Unlike its homologs in other eukaryotic organisms, which exclusively function as sensors for cyclic dinucleotides, shrimp STING has the ability to bind to both double-stranded DNA and cyclic dinucleotides, including 2'3'-cGAMP. In vivo, shrimp STING can directly sense DNA nucleic acids from an infected virus, accelerate IFN regulatory factor dimerization and nuclear translocation, induce the expression of an IFN functional analog protein (Vago4), and finally establish an antiviral state. Taken together, our findings unveil a novel double-stranded DNA-STING-IKKε-IRF-Vago antiviral axis in an arthropod, providing valuable insights into the functional origins of DNA-sensing pathways in evolution.

Dual-Functional AIE Fluorescent Probe for Visualization of Lipid Droplets and Photodynamic Therapy of Cancer.

Abnormal lipid droplets (LDs) are known to be intimately bound with the occurrence and development of cancer, allowing LDs to be critical biomarkers for cancers. Aggregation-induced emission luminogens (AIEgens), with efficient reactive oxygen species (ROS) production performance, are prime photosensitizers (PSs) for photodynamic therapy (PDT) with imaging. Therefore, the development of dual-functional fluorescent probes with aggregation-induced emission (AIE) characteristics that enable both simultaneous LD monitoring and imaging-guided PDT is essential for concurrent cancer diagnosis and treatment. Herein, we reported the development of a novel LD-targeting fluorescent probe (TDTI) with AIE performance, which was expected to realize the integration of cancer diagnosis through LD visualization and cancer treatment via PDT. We demonstrated that TDTI, with typical AIE characteristics and excellent photostability, could target LDs with high specificity, which enables the dynamic tracking of LDs in living cells, specific imaging of LDs in zebrafish, and the differentiation of cancer cells from normal cells for cancer diagnosis. Meanwhile, TDTI exhibited fast ROS generation ability (achieving equilibrium within 60 s) under white light irradiation (10 mW/cm2). The cell apoptosis assay revealed that TDTI effectively induced growth inhibition and apoptosis of HeLa cells. Further, the results of PDT in vivo indicated that TDTI had a good antitumor effect on the tumor-bearing mice model. Collectively, these results highlight the potential utility of the dual-functional fluorescent probe TDTI in the integrated diagnosis and treatment of cancer.

Sensitive Materials Used in Surface Acoustic Wave Gas Sensors for Detecting Sulfur-Containing Compounds.

There have been many studies on surface acoustic wave (SAW) sensors for detecting sulfur-containing toxic or harmful gases. This paper aims to give an overview of the current state of polymer films used in SAW sensors for detecting deleterious gases. By covering most of the important polymer materials, the structures and types of polymers are summarized, and a variety of devices with different frequencies, such as delay lines and array sensors for detecting mustard gas, hydrogen sulfide, and sulfur dioxide, are introduced. The preparation method of polymer films, the sensitivity of the SAW gas sensor, the limit of detection, the influence of temperature and humidity, and the anti-interference ability are discussed in detail. The advantages and disadvantages of the films are analyzed, and the potential application of polymer films in the future is also forecasted.

The predictive value of computed tomography value on high-resolution images in differentiating invasive from indolent lung adenocarcinoma.

Background: Invasive adenocarcinoma (IA) has a worse prognosis and different clinical management strategies compared to indolent lung adenocarcinoma including adenocarcinoma in situ (AIS) and minimally IA (MIA). The purpose of this study was to evaluate the predictive value of computed tomography (CT) value in differentiating invasive from indolent lung adenocarcinoma. Methods: The pathological diagnoses and imaging data of confirmed lung adenocarcinomas manifested as lung nodules with homogeneous internal density which were surgically resected between August 2021 and July 2022 were retrospectively analyzed. Differences in CT values between invasive and indolent lung adenocarcinomas were compared in the primary cohort (n=766), and receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off value. The predictive performance of the cut-off value was evaluated in the validation cohort (n=341). Results: A total of 1,107 lung nodules from 1,014 patients were included in the total cohort. The CT values had a significant difference between invasive and indolent lung adenocarcinomas (P<0.001). Using the primary cohort, we determined the optimal cut-off value of -415 Hounsfield units (HU) of the CT value based on ROC curve, which showed good discrimination between IA and AIS/MIA in both the primary and validation cohorts (sensitivity, 85.98% and 87.42%, specificity, 87.67% and 84.74%, respectively). Conclusions: The CT value of >-415 HU could be an effective predictor of invasive lung adenocarcinoma, thereby providing an appropriate clinical decision guide.

Application of a nomogram model for the prediction of 90-day poor outcomes following mechanical thrombectomy in patients with acute anterior circulation large-vessel occlusion.

Background: The past decade has witnessed advancements in mechanical thrombectomy (MT) for acute large-vessel occlusions (LVOs). However, only approximately half of the patients with LVO undergoing MT show the best/independent 90-day favorable outcome. This study aimed to develop a nomogram for predicting 90-day poor outcomes in patients with LVO treated with MT. Methods: A total of 187 patients who received MT were retrospectively analyzed. Factors associated with 90-day poor outcomes (defined as mRS of 4-6) were determined by univariate and multivariate logistic regression analyzes. One best-fit nomogram was established to predict the risk of a 90-day poor outcome, and a concordance index was utilized to evaluate the performance of the model. Additionally, 145 patients from a single stroke center were retrospectively recruited as the validation cohort to test the newly established nomogram. Results: The overall incidence of 90-day poor outcomes was 45.16%, affecting 84 of 186 patients in the training set. Moreover, five variables, namely, age (odds ratio [OR]: 1.049, 95% CI [1.016-1.083]; p = 0.003), glucose level (OR: 1.163, 95% CI [1.038-1.303]; p = 0.009), baseline National Institute of Health Stroke Scale (NIHSS) score (OR: 1.066, 95% CI [0.995-1.142]; p = 0.069), unsuccessful recanalization (defined as a TICI grade of 0 to 2a) (OR: 3.730, 95% CI [1.688-8.245]; p = 0.001), and early neurological deterioration (END, defined as an increase of ≥4 points between the baseline NIHSS score and the NIHSS score at 24 h after MT) (OR: 3.383, 95% CI [1.411-8.106]; p = 0.006), were included in the nomogram to predict the potential risk of poor outcomes at 90 days following MT in LVO patients, with a C-index of 0.763 (0.693-0.832) in the training set and 0.804 (0.719-0.889) in the validation set. Conclusion: The proposed nomogram provided clinical evidence for the effective control of these risk factors before or during the process of MT surgery in LVO patients.

Establishing and validation of the VBV score for assessing Lung ground-glass nodules based on high-resolution computed tomography.

BACKGROUND: The widespread utilization of chest High-resolution Computed Tomography (HRCT) has prompted detection of pulmonary ground-glass nodules (GGNs) in otherwise asymptomatic individuals. We aimed to establish a simple clinical risk score model for assessing GGNs based on HRCT. METHODS: We retrospectively analyzed 574 GGNs in 574 patients undergoing HOOK-WIRE puncture and pulmonary nodule surgery from January 2014 to November 2018. Clinical characteristics and imaging features of the GGNs were assessed. We analyzed the differences between malignant and benign nodules using binary logistic regression analysis and constructed a simple risk score model, the VBV Score, for predicting the malignancy status of GGNs. Then, we validated this model via other 1200 GGNs in 1041 patients collected from three independent clinical centers in 2022. RESULTS: For the exploratory phase of this study, out of the 574 GGNs, 481 were malignant and 93 were benign. Vacuole sign, air bronchogram, and intra-nodular vessel sign were important indicators of malignancy in GGNs. Then, we derived a VBV Score = vacuole sign + air bronchogram + intra-nodular vessel sign, to predict the malignancy of GGNs, with a sensitivity, specificity, and accuracy of 95.6%, 80.6%, and 93.2%, respectively. We also validated it on other 1200 GGNs, with a sensitivity, specificity, and accuracy of 96.0%, 82.6%, and 95.0%, respectively. CONCLUSIONS: Vacuole sign, air bronchogram, and intra-nodular vessel sign were important indicators of malignancy in GGNs. VBV Score showed good sensitivity, specificity, and accuracy for differentiating benign and malignant pulmonary GGNs.

Cancer burden and risk in the Chinese population aged 55 years and above: A systematic analysis and comparison with the USA and Western Europe.

Background: We analysed the cancer burden among elderly Chinese people over the age of 55 years and compared them to USA and Western Europe to explore the cancer model in China. Methods: We retrieved data on 29 cancers with 34 risk factors from the 2019 Global Burden of Disease database to evaluate the cancer burden in Chinese elderly individuals aged 55 years and older. We then used the age-standardised incidence rate (ASIR), age-standardised death rate (ASDR), age-standardised disability-adjusted life year (DALY) rate, and average annual percentage change (AAPC) to compare the characteristics and change trend of cancers among China, USA, and Western Europe. Results: In 2019, the number of incident cases of 29 cancers among people aged 55 years and above in China increased more than 3-fold compared to 1990, while the number of deaths and DALYs approximately doubled. We also found that the cancer population in China was ageing; meanwhile, the cancer burden became significantly higher for men than for women, and the gap between men and women had widened. Cancers with the highest cancer DALYs were lung cancer (13 444 500; 95% uncertainty interval (UI) = 11 307 100, 15 853 700), stomach cancer (7 303 900; 95% UI = 6 094 600, 8 586 500), oesophageal cancer (4 633 500; 95% UI = 3 642 500, 5 601 200), colon and rectum cancer (4 386 500; 95% UI = 3 769 500, 5 067 200), liver cancer (2 915 100, 95% UI = 2 456 300, 3 463 900), and pancreatic cancer (2 028 400; 95% UI = 1 725 000, 2 354 900). Compared with 1990, the DALY rate and incidence rate of stomach cancer, oesophageal cancer, and liver cancer had markedly decreased. The DALY rate and incidence rate of lung, colon, rectum, and pancreatic cancer had increased significantly, as did the incidence rate of breast cancer in women. Smoking and diet were the top two cancer risk factors, and the impact of ambient particulate matter pollution on cancer increased each year. The overall 29 cancers age-standardised DALY rate and ASDR in China, USA, and Western Europe were similar, and all showed downward trend in the past 30 years. Compared with the USA and Western Europe, the age-standardised DALY rate of liver, nasopharyngeal, oesophageal, stomach, and cervical cancers in China was more prominent. The age-standardised DALY rate of lung cancer and colon and rectum cancer decreased annually in Western Europe and the USA, but increased in China. Conclusions: Over the past 30 years, China had made progress in controlling stomach, oesophageal, and liver cancer. However, lung, colon, rectum, pancreatic, and breast cancers had become more prevalent, having risen alongside economic development. The risks of smoking and dietary were major issues that need to be addressed urgently. The cancer situation in China remains serious; future cancer prevention efforts need to balance economic development with people's physical health, identify key groups, improve the health environment of residents and guide them to live a healthy life, and expand the scope of cancer screening.

[Ultrasonic Composite Iron-carbon Activated Persulfate for Treating Organic Wastewater].

A coupling system of ultrasonic composite iron-carbon activated persulfate (US/PS/Fe-C) was built to treat a triphenylmethane derivative, crystal violet (CV). The results revealed that US/PS/Fe-C ternary system had a good coupling effect. The structure and surface morphology of commercial Fe-C and self-made Fe-C catalysts were analyzed using an X-ray diffractometer (XRD) and scanning electron microscope (SEM), respectively. Finally, commercial Fe-C was used to study the effects of different factors on the CV of US/PS/Fe-C ternary coupling degradation, and the optimum conditions were as follows:PDS concentration 2 mmol·L-1, iron-carbon catalyst 1 g·L-1, pH without adjustment, and the removal rate of 15 mg·L-1 CV reached 90% after 30 min. To explore the effects of anions and cations on the system, it was observed that Mg2+ and NO3- had almost no effect on the treatment of the system, and Mn2+, Cl-, and CO32- had a certain effect on the treatment of the system, whereas Fe2+ could promote the reaction at low concentration and inhibit the reaction at high concentration. By adding different quenchants, it was concluded that there were four types of active substances:1O2, SO4-·,·O2-, and·OH.

Pleiotrophin ameliorates age-induced adult hippocampal neurogenesis decline and cognitive dysfunction.

Cognitive impairment has been associated with an age-related decline in adult hippocampal neurogenesis (AHN). The molecular basis of declining neurogenesis in the aging hippocampus remains to be elucidated. Here, we show that pleiotrophin (PTN) expression is decreased with aging in neural stem and progenitor cells (NSPCs). Mice lacking PTN exhibit impaired AHN accompanied by poor learning and memory. Mechanistically, we find that PTN engages with protein tyrosine phosphatase receptor type Z1 (PTPRZ1) to promote NSPC proliferation and differentiation by activating AKT signaling. PTN overexpression or pharmacological activation of AKT signaling in aging mice restores AHN and alleviates relevant memory deficits. Importantly, we also find that PTN overexpression improves impaired neurogenesis in senescence-accelerated mouse prone 8 (SAMP8) mice. We further confirm that PTN is required for enriched environment-induced increases in AHN. These results corroborate the significance of AHN in aging and reveal a possible therapeutic intervention by targeting PTN.

Synthesis of a Red-Emitting Polarity-Sensitive Fluorescent Probe Based on ICT and Visualization for Lipid Droplet Dynamic Processes.

Abnormal lipid droplets (LDs) have been recognized as critical factors in many diseases because they are metabolically active and dynamic organelles. Visualization for LD dynamic processes is fundamental for elucidating the relationship of LDs and related diseases. Herein, a red-emitting polarity-sensitive fluorescent probe (TPA-CYP) based on intramolecular charge transfer (ICT) was proposed, which was constructed by employing triphenylamine (TPA) and 2-(5,5-dimethyl-2-cyclohex-1-ylidene)propanedinitrile (CYP) as electron donor and acceptor moiety, respectively. The spectra results underlined the excellent characteristics of TPA-CYP, such as high polarity sensitivity (Δf = 0.209 to 0.312), strong solvatochromic effect (λem 595-699 nm), and the large Stokes shifts (174 nm). Moreover, TPA-CYP exhibited a specific ability to target LDs and effectively differentiated cancer cells and normal cells. Surprisingly, TPA-CYP had been successfully applied to dynamic tracking of LDs, not only in inflammation induced by lipopolysaccharide (LPS), the process of oxidative stress, but also in live zebrafish. We believe that TPA-CYP could serve as a powerful tool to gain insight into the dynamics of LDs and to understand and diagnose LD-associated diseases.

Study on the Minimum Fire-Extinguishing Concentration of Several Commonly Used Extinguishing Agents to Suppress Pyrolysis Gas of Red Pine Wood.

The suppression of forest wood burning has been one of the important research directions in the field of solid combustible fire safety. The process of forest wood flame propagation is a coupled process of solid-phase pyrolysis and gas-phase combustion chemical reactions; therefore, as long as the solid-phase pyrolysis or gas-phase combustion can be suppressed, the forest wood flame propagation can be suppressed and an important contribution can be made to the subsequent suppression of forest wood fires. Previous studies have focused on the inhibition of solid-phase pyrolysis of forest wood, so this paper examines the effectiveness of several common fire suppressants for suppressing forest wood gas-phase flames, starting with the inhibition of forest wood gas-phase combustion. In this paper, for the convenience of the study, we narrowed the scope of the research object to the previous research ideas for gas fires, established a simplified small-scale flame model for forest wood fire suppression, took red pine wood as the research object, analyzed the pyrolysis gas components after high-temperature pyrolysis, and constructed a Cup burner suitable for N2, CO2, fine water mist, and NH4H2PO4 powder to extinguish the pyrolysis gas flame of red pine wood, respectively. The experimental system, together with the 9306 fogging system and the improved powder delivery control system, shows the process of extinguishing fuel flames such as red pine pyrolysis gas at 350, 450, and 550 °C with various types of fire-extinguishing agents on this device. It was found that the flame morphology was related to the composition of the gas and the type of extinguishing agent. At the same time, NH4H2PO4 powder appeared to burn above the cup mouth when pyrolysis gas interacted with it at 450 °C, but this phenomenon did not occur when other extinguishing agents interacted with it and only appeared when pyrolysis gas interacted with it at 450 °C, so it was judged that this phenomenon was related to the CO2 content of the gas component and the type of extinguishing agent. The study found that the four extinguishing agents extinguish red pine pyrolysis gas flame MEC value. There's a big difference. The worst performance is N2. Compared with N2 suppression of red pine pyrolysis gas flame, CO2 suppression effectiveness is 60% higher, but compared to the suppression effectiveness of fine water mist and far away, the suppression effectiveness of fine water mist is much higher than the suppression effectiveness of CO2. However, the difference in effectiveness between fine water mist and NH4H2PO4 powder is almost double. In summary, in the suppression of red pine gas-phase flame, four kinds of fire-extinguishing agents are ranked as follows: N2 < CO2 < fine water mist < NH4H2PO4 powder. Finally, the suppression mechanism of each type of extinguishing agent was analyzed. The study of this paper can provide some data to support the extinguishing of open fires in forest fires or suppressing the rate of forest fire spread.

Genotype-phenotype correlation in patients with 21-hydroxylase deficiency.

Introduction: 21-hydroxylase deficiency (21OHD) is the most common cause of congenital adrenal hyperplasia (CAH). However, patients with 21OHD manifest various phenotypes due to a wide-spectrum residual enzyme activity of different CYP21A2 mutations. Methods: A total of 15 individuals from three unrelated families were included in this study. Target Capture-Based Deep Sequencing and Restriction Fragment Length Polymorphism was conducted on peripheral blood DNA of the three probands to identify potential mutations/deletions in CYP21A2; Sanger sequencing was conducted with the DNA from the family members of the probands. Results: Dramatically different phenotypes were seen in the three probands of CAH with different compound heterozygous mutations in CYP21A2. Proband 1 manifested simple virilizing with mutations of 30-kb deletion/c.[188A>T;518T>A], the latter is a novel double mutants classified as SV associated mutation. Although both probands carry the same compound mutations [293-13C>G]:[518T>A], gonadal dysfunction and giant bilateral adrenal myelolipoma were diagnosed for proband 2 and proband 3, respectively. Conclusion: Both gender and mutations contribute to the phenotypes, and patients with the same compound mutations and gender could present with different phenotypes. Genetic analysis could help the etiologic diagnosis, especially for atypical 21OHD patients.

Signaling events induced by lipopolysaccharide-activated Toll in response to bacterial infection in shrimp.

Toll-like receptors (TLR) play a crucial role in the detection of microbial infections in vertebrates and invertebrates. Mammalian TLRs directly recognize a variety of structurally conserved microbial components. However, invertebrates such as Drosophila indirectly recognize microbial products by binding to the cytokine-like ligand Spätzle, which activates signaling cascades that are not completely understood. In this study, we investigated the signaling events triggered by Toll in response to lipopolysaccharide (LPS), a cell wall component of gram-negative bacteria, and Vibrio parahaemolyticus infection in the arthropod shrimp Litopenaeus vannamei. We found that five of the nine Tolls from L. vannamei bound to LPS and the RNAi of LvToll1, LvToll2, LvToll3, LvToll5, and LvToll9 weakened LvDorsal-L phosphorylation induced by V. parahaemolyticus. All nine Tolls combined with MyD88 via the TIR domain, thereby conferring signals to the tumor necrosis factor receptor-associated factor 6 (TRAF6)-transforming growth factor-ß activated kinase 1 binding protein 2 (TAB2)-transforming growth factor-ß activated kinase 1 (TAK1) complex. Further examination revealed that the LvTRAF6-LvTAB2-LvTAK1 complex contributes to Dorsal-L phosphorylation and nuclear translocation during V. parahaemolyticus infection. Overall, shrimp Toll1/2/3/5/9-TRAF6/TAB2/TAK1-Dorsal cascades protect the host from V. parahaemolyticus infection, which provides a better understanding of how the innate immune system recognizes and responds to bacterial infections in invertebrates.

Core strength training influences basketball players' body / A influência do treinamento de força do core no corpo de jogadores de basquete / La influencia del entrenamiento de la fuerza central en el cuerpo de los jugadores de baloncesto

ABSTRACT Introduction Modern basketball is very competitive and enjoyable; it combines several factors. Basketball requires specific physical characteristics such as high stature, which raises the position of the center of gravity, making the stability angle smaller. This compromises stability, especially in sudden speed and direction changes, because it requires a large base opening. The core musculature is intimately involved with body balance; however, there is a lack of studies verifying the impact of specific training of this region on balance in basketball athletes. Objective To explore the influence of core strengthening on the physical fitness of college basketball players. Methods 12 college basketball players were selected and randomly divided into a control group and an experimental group. The experimental group performed core strengthening training, while the control group practiced traditional strength training. After six weeks, physical fitness and basic skills were compared between the groups. Data were statistically treated and discussed confronting the literature. Results Basketball players in the experimental group obtained higher fast dribbling passes and shots than before the experiment (P<0.05), there was no statistically significant difference in several indicators in the control group ( P>0.05); Basketball players in the experimental group had higher fast dribbling passes and shots than the control group (P<0.05), there was no statistically significant difference in approach height between the experimental group and the control group (P>0.05). Conclusion Core strengthening training can improve the physical fitness of college basketball players. Evidence level II; Therapeutic Studies - Investigating the results.

RESUMO Introdução O basquete moderno é muito competitivo e prazeroso, é uma combinação de vários fatores. O basquetebol exige características físicas específicas como a alta estatura, que eleva a posição do centro de gravidade, tornando o ângulo de estabilidade menor. Isso compromete a estabilidade, principalmente nas mudanças repentinas de velocidade e direção pois exige grande abertura de base. A musculatura do core está intimamente envolvida com o equilíbrio corporal, entretanto faltam estudos verificando o impacto do treino específico dessa região no equilíbrio em atletas de basquetebol. Objetivo Explorar a influência do fortalecimento do core na aptidão física dos jogadores universitários de basquete. Métodos 12 universitários jogadores de basquete foram selecionados e aleatoriamente divididos em grupo controle e grupo experimental. O experimental realizou treino fortalecimento do core, enquanto o controle praticava treinamento de força tradicional. Após seis semanas, comparou-se a aptidão física e habilidades básicas entre os grupos. Os dados foram tratados estatisticamente e discutidos confrontando a literatura. Resultados Os jogadores de basquete do grupo experimental obtiveram maiores passes rápidos de drible e arremessos do que antes do experimento (P<0,05), não houve diferença estatisticamente significativa em vários indicadores no grupo controle ( P>0,05); Os jogadores de basquete do grupo experimental apresentaram maiores passes e arremessos de drible rápido do que o grupo controle (P<0,05), não houve diferença estatisticamente significativa na altura de aproximação entre o grupo experimental e o grupo controle (P>0,05). Conclusão O treino de fortalecimento do core pode melhorar a aptidão física de jogadores universitários de basquete. Nível de evidência II; Estudos terapêuticos - Investigação de resultados.

RESUMEN Introducción El baloncesto moderno es muy competitivo y divertido, es una combinación de varios factores. El baloncesto exige características físicas específicas como la alta estatura, que eleva la posición del centro de gravedad, haciendo que el ángulo de estabilidad sea menor. Esto compromete la estabilidad, sobre todo en los cambios bruscos de velocidad y dirección, porque exige una gran apertura de la base. Los músculos del core están íntimamente implicados con el equilibrio corporal, sin embargo, faltan estudios que verifiquen el impacto del entrenamiento específico de esta región sobre el equilibrio en los deportistas de baloncesto. Objetivo Explorar la influencia del fortalecimiento del núcleo en la aptitud física de los jugadores universitarios de baloncesto. Métodos Se seleccionaron 12 jugadores de baloncesto universitario y se dividieron aleatoriamente en un grupo de control y un grupo experimental. Los experimentales realizaron un entrenamiento de fortalecimiento del núcleo, mientras que los de control practicaron un entrenamiento de fuerza tradicional. Después de 6 semanas, se comparó la aptitud física y las habilidades básicas entre los grupos. Los datos fueron tratados estadísticamente y discutidos confrontándolos con la literatura. Resultados Los jugadores de baloncesto del grupo experimental obtuvieron pases y tiros rápidos más altos que antes del experimento (P<0,05), no hubo diferencias estadísticamente significativas en varios indicadores en el grupo de control ( P>0,05); Los jugadores de baloncesto del grupo experimental tuvieron pases y tiros rápidos más altos que el grupo de control (P<0,05), no hubo diferencias estadísticamente significativas en la altura de aproximación entre el grupo experimental y el grupo de control (P>0,05). Conclusión El entrenamiento de fortalecimiento del núcleo puede mejorar la condición física de los jugadores de baloncesto universitarios. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

Global, regional, and national burden of uterine fibroids in the last 30 years: Estimates from the 1990 to 2019 Global Burden of Disease Study.

Objective: To study specific information on trends in incidence, mortality, disability-adjusted life years (DALY) and the corresponding trends among five sociodemographic index regions, 21 regions, and 204 countries for decision-making, which would enable policymakers to distribute limited resources and devise policies more rationally. Methods: Data on uterine fibroids (UNs) from 1990 to 2019, including incidence, mortality, and DALYs, were obtained from the 2019 Global Burden of Disease Study. An estimated annual percentage change (EAPC) was calculated to assess morbidity, mortality, and DALY trends. Results: The incident cases of UFs increased from 5,769,658 (95%UI, 7,634,3995-4,274,824) incidences in 1990 to 9,643,336 (95%UI, 7,178,053-12,714,741) incidences in 2017, and the age-standardized incidence rate was steady at 225.67/100,000 persons (95%UI, 167.33-298.87) in 1990 to 241.18/100,000 persons (95%UI, 179,45-318.02) in 2019. The incidence ratio in the high sociodemographic index (SDI) region showed a unimodal distribution, with peaks in 2005. Between 2009 and 2017, the age-standardized death rate of UFs declined globally, especially in low-SDI and low-middle SDI regions. In contrast with 860,619 DALYs (95%UI, 473,067-1,505,289) in 1990, the number of DALYs was 1,378,497 (95%UI, 710,915-2,475,244) in 2019, which had increased significantly, whereas the age-standardized DALY rate decreased expressively with an EAPC of -1.93 (95%CI, from -2.16 to -1.71). Conclusion: The global burden of UFs increased between 1990 and 2019, and the incidences and DALYs increased prominently worldwide, while the deaths from UFs had no evident growth. Lower SDI regions carried an incremental burden of UFs, while disease reduction was observed in higher SDI regions. It is high time we paid attention to the underprivileged regional quality of life and health protection.

Comparison of percutaneous transforaminal endoscopic discectomy and open lumbar discectomy for lumbar disc herniations: A systematic review and meta-analysis.

Purpose: In order to compare the outcomes of percutaneous transforaminal endoscopic discectomy (PTED) and open lumbar discectomy (OLD) for lumbar disc herniation (LDH). Methods: The Pubmed, Cochrane Library, Web of Sience, Embase, Clinicaltrials.gov, CBM, CNKI, VIP, Wangfang databases were searched from inception to April 30, 2022 to collect the published studies about PTED vs. OLD for treatment of LDH. The Revman 5.2 was used for data analysis. The primary outcomes were excellent rates, complication rates and reoperation rates. The secondary outcomes were length of incision, length of operation, length of hospital stay, and the amount of intraoperative blood loss. Results: A total of nine studies were included, of which, eight randomized controlled trials and one retrospective study involving 1,679 patients with LDH (755 patients for PTED, and 924 patients for OLD) were included. According to meta-analysis, there were no significant difference in excellent rates (odds ratio [OR] = 1.47, 95% confidence intervals [CI]: 0.94-2.28, P = 0.09), reoperation rates (OR = 0.96, 95% CI: 0.50-1.84, P = 0.90), length of operation [standardized mean differences (SMD) = -17.97, 95%CI: -54.83-18.89, P = 0.34], and the amount of intraoperative blood loss (SMD = -128.05, 95%CI: -258.67-2.57, P = 0.05), respectively. There were significant differences in complication rates (OR = 0.22, 95% CI: 0.14-0.33, P < 0.001), length of incision (SMD = -2.76, 95%CI: -2.88--2.65, P < 0.001), and length of hospital stay (SMD = -5.19, 95%CI: -5.36--5.01, P < 0.001), respectively. Conclusions: PTED can achieve better outcomes with respect to the complication rates, length of incision, and length of hospital stay compared with OLD.

Unilateral Biportal Endoscopic Discectomy versus Microendoscopic Discectomy for the Treatment of Lumbar Spinal Stenosis: A Systematic Review and Meta-Analysis.

Objective: In minimally invasive spinal surgery, the treatment of lumbar spinal stenosis with microendoscopic discectomy (MED) or unilateral biportal endoscopic discectomy (UBED) shows effective results, but which is more effective is controversial. Our study aimed to evaluate the efficacy and safety of UBED versus MED in the treatment of lumbar spinal stenosis by a systematic review and meta-analysis, so as to provide reference for the promotion of UBED in clinical practice. Methods: The multiple databases like PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Databases, Chinese BioMedical Database, and Wanfang Database were used to search for the relevant studies. Review Manager 5.4 was adopted to estimate the effects of the results among selected articles. Odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were used to estimate the overall pooled effect. Subgroup analysis, forest plots, funnel plots and Egger's test for the articles included were also conducted. Results: Three randomized clinical trials and seven cohort studies were finally retrieved, these studies included 685 and 829 patients in the UBED and MED groups, respectively. There were no differences in terms of operation time (MD = -0.92, P =0.72), estimated blood loss (MD = -26.31, P =0.08), complications (MD =0.81, P =0.38) and Oswestry Disability Index (ODI) score (P >0.05 in four subgroup) between the two groups. The visual analog scale (VAS) score of back pain in the UBED group was better than MED group only at 6 months (MD = -0.23, P =0.006) after operation, the VAS score of leg pain in the UBED group was better than that of MED group at 3 mouths (MD = -0.22, P =0.002) and 6 months (MD = -0.24, P =0.006) after operation, the UBED group had a less postoperative length of stay than the MED group (MD = -1.85, P <0.001). The bias analysis showed that there was no potential publication bias in the included literature. Conclusion: This study showed that compared with MED, UBED has the advantages of short hospital stay and good short-term curative effect, but there is no significant difference in long-term efficacy and safety, they can be replaced by each other in clinical application.