Amelioration of nonalcoholic fatty liver disease by inhibiting the deubiquitylating enzyme RPN11.

Nonalcoholic fatty liver disease (NAFLD), including its more severe manifestation nonalcoholic steatohepatitis (NASH), is a global public health challenge. Here, we explore the role of deubiquitinating enzyme RPN11 in NAFLD and NASH. Hepatocyte-specific RPN11 knockout mice are protected from diet-induced liver steatosis, insulin resistance, and steatohepatitis. Mechanistically, RPN11 deubiquitinates and stabilizes METTL3 to enhance the m6A modification and expression of acyl-coenzyme A (CoA) synthetase short-chain family member 3 (ACSS3), which generates propionyl-CoA to upregulate lipid metabolism genes via histone propionylation. The RPN11-METTL3-ACSS3-histone propionylation pathway is activated in the livers of patients with NAFLD. Pharmacological inhibition of RPN11 by Capzimin ameliorated NAFLD, NASH, and related metabolic disorders in mice and reduced lipid contents in human hepatocytes cultured in 2D and 3D. These results demonstrate that RPN11 is a novel regulator of NAFLD/NASH and that suppressing RPN11 has therapeutic potential for the treatment.

Epidemiological features and temporal trends of the co-infection between HIV and tuberculosis, 1990-2021: findings from the Global Burden of Disease Study 2021.

BACKGROUND: The co-infection of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and tuberculosis (TB) poses a significant clinical challenge and is a major global public health issue. This study aims to elucidate the disease burden of HIV-TB co-infection in global, regions and countries, providing critical information for policy decisions to curb the HIV-TB epidemic. METHODS: The ecological time-series study used data from the Global Burden of Disease (GBD) Study 2021. The data encompass the numbers of incidence, prevalence, mortality, and disability-adjusted life year (DALY), as well as age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and DALY rate for HIV-infected drug-susceptible tuberculosis (HIV-DS-TB), HIV-infected multidrug-resistant tuberculosis (HIV-MDR-TB), and HIV-infected extensively drug-resistant tuberculosis (HIV-XDR-TB) from 1990 to 2021. from 1990 to 2021. The estimated annual percentage change (EAPC) of rates, with 95% confidence intervals (CIs), was calculated. RESULTS: In 2021, the global ASIR for HIV-DS-TB was 11.59 per 100,000 population (95% UI: 0.37-13.05 per 100,000 population), 0.55 per 100,000 population (95% UI: 0.38-0.81 per 100,000 population), for HIV-MDR-TB, and 0.02 per 100,000 population (95% UI: 0.01-0.03 per 100,000 population) for HIV-XDR-TB. The EAPC for the ASIR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.71 (95% CI: 1.92-7.59) and 13.63 (95% CI: 9.44-18.01), respectively. The global ASMR for HIV-DS-TB was 2.22 per 100,000 population (95% UI: 1.73-2.74 per 100,000 population), 0.21 per 100,000 population (95% UI: 0.09-0.39 per 100,000 population) for HIV-MDR-TB, and 0.01 per 100,000 population (95% UI: 0.00-0.03 per 100,000 population) for HIV-XDR-TB in 2021. The EAPC for the ASMR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.78 (95% CI: 1.32-8.32) and 10.00 (95% CI: 6.09-14.05), respectively. CONCLUSIONS: The findings indicate that enhancing diagnostic and treatment strategies, strengthening healthcare infrastructure, increasing access to quality medical care, and improving public health education are essential to combat HIV-TB co-infection.

Study on the sliding mechanism of the external dump slope in the open-pit mine with wind-blown sand base.

Wind-blow sand (WBS) is widely distributed in the "Desert Gobi" region. This study is aimed at exploring the mechanism of how different thicknesses of the WBS layer influence the slope movement of external dumps in open-pit mines. To achieve this aim, the slope of the external dump in the open-pit mining area of Panel 3 in Daliuta Coal Mine was taken as the research object. First, similar simulation experiments were performed for investigating the failure modes and deformation characteristics of the external dump slopes under three geo-morphological conditions: loess base, 10-m-thick WBS base, and 20-m-thick WBS base, respectively. The following results were obtained from the experiments. For the slope with a loess base, its failure is mainly caused by circular sliding from the dump to the interior of the loess layer. For the slope with a 10-m-thick WBS base, the sliding mode involves circular sliding from the dump area to the interior of the WBS layer, linear sliding along the WBS base, and shearing along the foot of the dump area. For the slope with a 20-m-thick WBS base, the sliding mode is circular sliding from the dump area to the interior of the WBS layer. Besides, the sliding area of the dump slope expands as the WBS layer thickens. Furthermore, the results of similar simulation experiments were verified by the finite difference software FLAC3D based on the strength reduction method, and an equation of relationship between the safety factor of the dump slope with a WBS base and the thickness of the WBS layer was derived.

[Study on the difference and clinical value of serum amino acids in patients with laryngeal squamous cell carcinoma].

Objective:To detect the differences in types and levels of amino acids in the peripheral serum of patients with laryngeal squamous cell carcinoma and non-tumor patients, and explore their relationship with clinical parameters of laryngeal squamous cell carcinoma as well as their clinical value in diagnosis. Methods:High-performance liquid chromatography-tandem mass spectrometry（HPLC-MS） was employed to detect the serum amino acid contents and levels of 62 patients diagnosed with laryngeal carcinoma and 141 non-tumor patients at the First Affiliated Hospital of Jinzhou Medical University between September 2018 and February 2021. The study compared the differences in 22 non-essential and essential amino acids found in the serum between the experimental group and the control group. An ROC curve and risk scoring formula of multivariate linear logic regression model was utilized to evaluate the efficiency of serum amino acids in the early diagnosis of laryngeal carcinoma. Results:There were significant differences in the contents of fourteen types of amino acids between the experimental and control groups, with thirteen amino acids showing higher levels in the experimental group（P<0.05）. Seven of these amino acids were essential, including phenylalanine, threonine, leucine, valine, histidine, tyrosine, and citrulline. The other six amino acids were non-essential, including arginine, asparagine, cysteine, glycine, ornithine, and proline. Interestingly, the content of homocysteine in the experimental group was lower than that in the control group（P=0.024）. Further analysis showed that patients with laryngeal squamous cell carcinoma in TNM stage Ⅰ and Ⅱ had higher serum methionine levels compared to those in stages Ⅲ and Ⅳ（P=0.026）. In addition, the content of serum histidine was higher in patients with poorly differentiated squamous cell carcinoma compared to those with well-differentiated squamous cell carcinoma（P=0.041）. The level of asparagine in the serum of patients with laryngeal squamous cell carcinoma older than 64 years old was lower than that in patients younger than 64 years old（P=0.033）. The level of tryptophan in the serum of patients with a smoking history was lower than that in patients without a smoking history（P=0.033）. The level of citrulline in the serum of patients with a history of alcohol consumption was higher than that in patients with no history of alcohol consumption（P=0.003）. ROC curve analysis showed that out of the 14 different amino acids between the experimental and control groups, citrulline and cysteine were relatively effective as independent factors in the diagnosis of laryngeal squamous cell carcinoma, with an AUC of 0.856 and 0.850, respectively. Arginine was the most sensitive factor in the diagnosis of laryngeal squamous cell carcinoma（AUC=0.855）. However, citrulline alone had the highest specificity（0.830） in the diagnosis of laryngeal squamous cell carcinoma, and the combination of 12 amino acids significantly improved the diagnostic efficiency of laryngeal squamous cell carcinoma, with an AUC of 0.946, sensitivity of 0.887, and specificity of 0.894. A risk score formula for a multivariate logistic regression model was established based on the differential amino acid content in the serum. The risk score of laryngeal squamous cell carcinoma group was higher than that of the non-tumor group（P<0.001）. The AUC of risk score in the diagnosis of laryngeal squamous cell carcinoma was 0.953 with sensitivity and specificity of 0.957 and 0.855. Conclusion:This study found that there are differences in the contents of 14 amino acids among which 13 amino acids were increased in serum of patients with laryngeal squamous cell carcinoma, and were associated with age, clinical stage, pathological differentiation, smoking, and drinking. Combined detection of 12 amino acids can improve the diagnostic efficiency of laryngeal squamous cell carcinoma and serve as potential markers for the auxiliary diagnosis of laryngeal squamous cell carcinoma using peripheral blood samples. Additionally, the established risk score model was found to be more effective in the diagnosis of laryngeal squamous cell carcinoma, indicating its important potential value as an auxiliary diagnostic tool.

Room temperature synthesis of a chiral covalent organic framework core-shell composite for high-performance liquid chromatography enantioseparation.

In this article, chiral covalent organic framework core-shell composite CCOF-TpPa-Py@SiO2 was facilely synthesized by induction at room temperature. The CCOF-TpPa-Py@SiO2 core-shell composite was used as a chiral stationary phase for the separation of the racemates by high-performance liquid chromatography, which exhibits good separation performance for chiral compounds including ketones, alcohols, esters, epoxides, carboxylic acids, amides, and amines. The effects of analyte injection mass on the enantioseparation were studied. The reproducibility and stability of the CCOF-TpPa-Py@SiO2 chiral column were explored. The intra-day (n = 5), inter-day (n = 5), and inter-column (n = 3) relative standard deviations for the migration times and resolution of benzoin were 0.32%-0.54%, 0.45%-0.61%, and 1.21%-1.53%, respectively. In addition, the chiral separation ability of the CCOF-TpPa-Py@SiO2 chiral column (column A) was compared with that of the MDI-ß-CD-Modified COF@SiO2 (column B) as well as a commercial chiral column (Chiralpak AD-H). The chiral recognition ability of column A is complementary to that of column B and AD-H column. The resolution mechanism of CCOF-TpPa-Py@SiO2 stationary phase towards chiral analyte was explored. Hence, the synthesis of CCOF-TpPa-Py@SiO2 core-shell composite by induction at room temperature as chiral stationary phases for chromatographic separation has important research potential and application prospects.

Oral microbiota diversity in moderate to severe plaque psoriasis, nail psoriasis and psoriatic arthritis.

Gaining a comprehensive understanding of the role played by the oral microbiome in moderate to severe plaque psoriasis and its potential implications for disease management and development holds significant importance. With the objective of exploring correlations between the oral microbiota and severe psoriasis, this study involved 72 severe psoriasis patients and 16 healthy individuals, whose clinical manifestations and living habits were carefully recorded. Cutting-edge techniques such as 16S rRNA gene sequencing and bioinformatics analysis were employed to compare the microbial flora, investigating dynamic changes among severe plaque psoriasis patients, psoriatic arthritis patients and healthy individuals. The findings revealed noteworthy patterns including increased levels of Aggregatibacter in the psoriatic arthritis group, accompanied by a decrease in the level of Prevotella. Moreover, the enrichment o Capnocytandophaga (P = 0.009), Campylobacter (P = 0.0022), and Acetobacter (P = 0.0292) was notably more substantial in the psoriasis group compared to the control group, whereas certain bacterial species such as Bacteroides (P = 0.0049), Muribaculaceae (P = 0.0048) demonstrated decreased enrichment. Additionally, the psoriatic arthritis group exhibited significantly higher levels of Ralstonia, Bifidobacterium and Micromonospora. Based on these findings, it can be inferred that individuals with lower levels of Prevotella and higher levels of Corynebacterium may be more susceptible to psoriasis exacerbation.

Genomic and Metagenomic Insights into the Distribution of Nicotine-degrading Enzymes in Human Microbiota.

Introduction: Nicotine degradation is a new strategy to block nicotine-induced pathology. The potential of human microbiota to degrade nicotine has not been explored. Aims: This study aimed to uncover the genomic potentials of human microbiota to degrade nicotine. Methods: To address this issue, we performed a systematic annotation of Nicotine-Degrading Enzymes (NDEs) from genomes and metagenomes of human microbiota. A total of 26,295 genomes and 1,596 metagenomes for human microbiota were downloaded from public databases and five types of NDEs were annotated with a custom pipeline. We found 959 NdhB, 785 NdhL, 987 NicX, three NicA1, and three NicA2 homologs. Results: Genomic classification revealed that six phylum-level taxa, including Proteobacteria, Firmicutes, Firmicutes_A, Bacteroidota, Actinobacteriota, and Chloroflexota, can produce NDEs, with Proteobacteria encoding all five types of NDEs studied. Analysis of NicX prevalence revealed differences among body sites. NicX homologs were found in gut and oral samples with a high prevalence but not found in lung samples. NicX was found in samples from both smokers and non-smokers, though the prevalence might be different. Conclusion: This study represents the first systematic investigation of NDEs from the human microbiota, providing new insights into the physiology and ecological functions of human microbiota and shedding new light on the development of nicotine-degrading probiotics for the treatment of smoking-related diseases.

The Effect of Allulose on the Attenuation of Glucose Release from Rice in a Static In Vitro Digestion Model.

Allulose is a rare sugar that provides <10% of the energy but 70% of the sweetness of sucrose. Allulose has been shown to attenuate glycemic responses to carbohydrate-containing foods in vivo. This study aimed to determine the optimal allulose dose for minimizing in vitro glucose release from rice compared to a rice control and fructose. A triphasic static in vitro digestion method was used to evaluate the in vitro digestion of a rice control compared to the co-digestion of rice with allulose (10 g, 20 g, and 40 g) and fructose (40 g). In vitro glucose release was affected by treatment (p < 0.001), time (p < 0.001), and treatment-by-time interaction (p = 0.002). Allulose (40 g) resulted in a reduction in in vitro glucose release from rice alone and rice digested with allulose (10 g), allulose (20 g), and fructose. The incremental area under the curve (iAUC) for in vitro glucose release was lower after allulose (40 g) (p = 0.005) compared to rice control and allulose (10 g) but did not differ from allulose (20 g) or fructose. This study demonstrates that allulose reduces glucose release from carbohydrates, particularly at higher doses, underscoring its potential as a food ingredient with functional benefits.

TMEM16F Expressed in Kupffer Cells Regulates Liver Inflammation and Metabolism to Protect Against Listeria Monocytogenes.

Infection by bacteria leads to tissue damage and inflammation, which need to be tightly controlled by host mechanisms to avoid deleterious consequences. It is previously reported that TMEM16F, a calcium-activated lipid scramblase expressed in various immune cell types including T cells and neutrophils, is critical for the control of infection by bacterium Listeria monocytogenes (Lm) in vivo. This function correlated with the capacity of TMEM16F to repair the plasma membrane (PM) damage induced in T cells in vitro, by the Lm toxin listeriolysin O (LLO). However, whether the protective effect of TMEM16F on Lm infection in vivo is mediated by an impact in T cells, or in other cell types, is not determined. Herein, the immune cell types and mechanisms implicated in the protective effect of TMEM16F against Lm in vivo are elucidated. Cellular protective effects of TMEM16F correlated with its capacity of lipid scrambling and augment PM fluidity. Using cell type-specific TMEM16F-deficient mice, the indication is obtained that TMEM16F expressed in liver Kupffer cells (KCs), but not in T cells or B cells, is key for protection against Listeria in vivo. In the absence of TMEM16F, Listeria induced PM rupture and fragmentation of KCs in vivo. KC death associated with greater liver damage, inflammatory changes, and dysregulated liver metabolism. Overall, the results uncovered that TMEM16F expressed in Kupffer cells is crucial to protect the host against Listeria infection. This influence is associated with the capacity of Kupffer cell-expressed TMEM16F to prevent excessive inflammation and abnormal liver metabolism.

Disulfidptosis-related long non-coding RNA signature predicts the prognosis, tumor microenvironment, immunotherapy, and antitumor drug options in colon adenocarcinoma.

This study aims to investigate the role and prognostic significance of long non-coding RNAs (lncRNAs) associated with disulfidptosis in colon adenocarcinoma (COAD). The TCGA database's clinical data and transcriptome profiles were employed. Analysis of previous studies identified 10 disulfidptosis-related genes (DRGs). We used these genes to construct a signature that could independently and accurately predict the prognosis of patients with COAD. The Kaplan-Meier (K-M) curve analysis showed that the lower-risk group had a better prognosis. With the help of multivariate Cox regression analysis, the risk score produced from the patient's signature might independently predict the outcomes. Utilizing a nomogram, the receiver operating characteristic (ROC) curve, and principal component analysis (PCA), the signature's predictive ability was also confirmed. It's interesting to note that immunotherapy, especially PD-1 immune checkpoint suppression, was more likely to benefit low-risk patients. The IC50 levels for certain anticancer agents were lower in the high-risk group. Finally, qRT-PCR analyses in colon cancer cell lines revealed elevated levels of lncRNAs CASC9, ZEB1-AS1, ATP2A1-AS1, SNHG7, AL683813.1, and AP003555.1, and reduced levels of FAM160A1-DT and AC112220.2, compared to normal cell lines. This signature offers insights into prognosis, tumor microenvironment, and options for immunotherapy and antitumor drugs in patients with COAD.

Integrated multi-omics analysis reveals molecular changes associated with chronic lipid accumulation following contusive spinal cord injury.

Functional and pathological recovery after spinal cord injury (SCI) is often incomplete due to the limited regenerative capacity of the central nervous system (CNS), which is further impaired by several mechanisms that sustain tissue damage. Among these, the chronic activation of immune cells can cause a persistent state of local CNS inflammation and damage. However, the mechanisms that sustain this persistent maladaptive immune response in SCI have not been fully clarified yet. In this study, we integrated histological analyses with proteomic, lipidomic, transcriptomic, and epitranscriptomic approaches to study the pathological and molecular alterations that develop in a mouse model of cervical spinal cord hemicontusion. We found significant pathological alterations of the lesion rim with myelin damage and axonal loss that persisted throughout the late chronic phase of SCI. This was coupled by a progressive lipid accumulation in myeloid cells, including resident microglia and infiltrating monocyte-derived macrophages. At tissue level, we found significant changes of proteins indicative of glycolytic, tricarboxylic acid cycle (TCA), and fatty acid metabolic pathways with an accumulation of triacylglycerides with C16:0 fatty acyl chains in chronic SCI. Following transcriptomic, proteomic, and epitranscriptomic studies identified an increase of cholesterol and m6A methylation in lipid-droplet-accumulating myeloid cells as a core feature of chronic SCI. By characterizing the multiple metabolic pathways altered in SCI, our work highlights a key role of lipid metabolism in the chronic response of the immune and central nervous system to damage.

Advancements and applications of loop-mediated isothermal amplification technology: a comprehensive overview.

Loop-mediated isothermal amplification (LAMP) is a novel method for nucleic acid detection known for its isothermal properties, high efficiency, sensitivity, and specificity. LAMP employs 4 to 6 primers targeting 6 to 8 regions of the desired sequence, allowing for amplification at temperatures between 60 and 65°C and the production of up to 109 copies within a single hour. The product can be monitored by various methods such as turbidimetry, fluorometry, and colorimetry. However, it faces limitations such as the risk of non-specific amplification, challenges in primer design, unsuitability for short gene sequences, and difficulty in multiplexing. Recent advancements in polymerase and primer design have enhanced the speed and convenience of the LAMP reaction. Additionally, integrating LAMP with technologies like rolling circle amplification (RCA), recombinase polymerase amplification (RPA), and CRISPR-Cas systems has enhanced its efficiency. The combination of LAMP with various biosensors has enabled real-time analysis, broadening its application in point-of-care testing (POCT). Microfluidic technology has further facilitated the automation and miniaturization of LAMP assays, allowing for the simultaneous detection of multiple targets and preventing contamination. This review highlights advancements in LAMP, focusing on primer design, polymerase engineering, and its integration with other technologies. Continuous improvements and integration of LAMP with complementary technologies have significantly enhanced its diagnostic capabilities, making it a robust tool for rapid, sensitive, and specific nucleic acid detection with promising implications for healthcare, agriculture, and environmental monitoring.

A bioactive supramolecular and covalent polymer scaffold for cartilage repair in a sheep model.

Regeneration of hyaline cartilage in human-sized joints remains a clinical challenge, and it is a critical unmet need that would contribute to longer healthspans. Injectable scaffolds for cartilage repair that integrate both bioactivity and sufficiently robust physical properties to withstand joint stresses offer a promising strategy. We report here on a hybrid biomaterial that combines a bioactive peptide amphiphile supramolecular polymer that specifically binds the chondrogenic cytokine transforming growth factor ß-1 (TGFß-1) and crosslinked hyaluronic acid microgels that drive formation of filament bundles, a hierarchical motif common in natural musculoskeletal tissues. The scaffold is an injectable slurry that generates a porous rubbery material when exposed to calcium ions once placed in cartilage defects. The hybrid material was found to support in vitro chondrogenic differentiation of encapsulated stem cells in response to sustained delivery of TGFß-1. Using a sheep model, we implanted the scaffold in shallow osteochondral defects and found it can remain localized in mechanically active joints. Evaluation of resected joints showed significantly improved repair of hyaline cartilage in osteochondral defects injected with the scaffold relative to defects injected with the growth factor alone, including implantation in the load-bearing femoral condyle. These results demonstrate the potential of the hybrid biomimetic scaffold as a niche to favor cartilage repair in mechanically active joints using a clinically relevant large-animal model.

Kinetics study on the low-temperature soda roasting of boron-rich blast furnace slag.

The method of preparing borax by low-temperature soda roasting and water leaching of boron-rich blast furnace slag (BRBFS) is a novel method for extracting boron from BRBFS. In order to further improve the water leaching rate of boron, this article mainly studied the low-temperature soda roasting kinetics of BRBFS. The effects of roasting temperature and Na2CO3 addition on the water leaching rate of boron were investigated. The results demonstrate that when the amount of Na2CO3 added is four times of the theoretical amount, the kinetics of NaBO2 formation can be described by the Nucleation (Avrami) model in the temperature range of 600-700 °C. The corresponding apparent activation energy is 54.45 kJ/mol, and the apparent frequency factor is 215.16 h-1. It was found that at a roasting temperature of 700 °C,when the amount of sodium carbonate added is twice, three times, and four times of the theoretical amount, the kinetics of NaBO2 formation matches with 3-D Diffusion (Jander) model, Nucleation and Growth (Avrami-Erofeev) model, and Nucleation (Avrami) model, respectively. With an increase in the amount of Na2CO3 added, the rate-controlling step for the formation of NaBO2 transitions from being diffusion-controlled to nucleation-controlled.

Nobiletin Regulates Polyinosinic-polycytidylic Acid-induced Inflammation in Macrophages Partially via the PPAR-γ Signaling Pathway.

INTRODUCTION: Macrophage dysregulation is a common pathogenic feature of viruses that provides extensive targets for antiviral therapy. Nobiletin, a polymethoxylated flavonoid found in citrus fruits, has a multitude of effects. METHODS: We investigated the effect of nobiletin on polyinosinic-polycytidylic acid (poly(I:C))-induced inflammation in RAW264.7 cells. Nobiletin inhibited the production of poly(I:C)-induced inflammatory factors, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and CXCL10. High-throughput sequencing revealed that nobiletin inhibited the expression of TNF-α, IL-6, and CXCL10 and promoted the expression of CD206, Chil3, and Vcam1. In the Kyoto Encyclopedia of Genes and Genomes enrichment analyses, the upregulated differential genes were significantly enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. RESULTS: The PPAR-γ inhibitor T0070907 significantly reversed the inhibitory effects of nobiletin on IL-6 and CXCL10 but had no significant effect on TNF-α secretion. CONCLUSION: Thus, nobiletin regulated poly(I:C)-induced inflammatory responses in RAW264.7 cells partially via the PPAR-γ signaling pathway.

Infection and biogeographical characteristics of Paragonimus westermani and P. skrjabini in humans and animal hosts in China: A systematic review and meta-analysis.

BACKGROUND: Paragonimiasis, primarily caused by Paragonimus westermani and P. skrjabini in China, is a common food-borne parasitic zoonosis. However, the national distribution of Paragonimus spp. infection and its associated environmental determinants remain poorly understood. In this paper, we summarize the infection of P. westermani and P. skrjabini and describe key biogeographical characteristics of the endemic areas in China. METHODS: Data on Paragonimus infection in humans and animal hosts were extracted from eight electronic databases, including CNKI, CWFD, Chongqing VIP, SinoMed, Medline, Embase, PubMed, and Web of Science. A random-effects meta-analysis model was used to estimate the pooled prevalence. All survey locations were georeferenced and plotted on China map, and scatter plots were used to illustrate the biogeographical characteristics of regions reporting Paragonimus infection. RESULTS: A total of 28,948 cases of human paragonimiasis have been documented, with 2,401 cases reported after 2010. Among the 11,443 cases with reported ages, 88.05% were children or adolescents. The pooled prevalence of P. skrjabini is 0.45% (95% CI: 0.27-0.66%) in snails, 31.10% (95% CI: 24.77-37.80%) in the second intermediate host, and 20.31% (95% CI: 9.69-33.38%) in animal reservoirs. For P. westermani, the pooled prevalence is 0.06% (95% CI: 0.01-0.13%) in snails, 52.07% (95% CI: 43.56-60.52%) in the second intermediate host, and 21.40% (95% CI: 7.82-38.99%) in animal reservoirs. Paragonimus are primarily distributed in regions with low altitude, high temperature, and high precipitation. In northeastern China, only P. westermani infections have been documented, while in more southern areas, infections of both P. westermani and P. skrjabini have been reported. CONCLUSIONS: Paragonimiasis remains prevalent in China, particularly among children and adolescents. Variations exist in the intermediate hosts and geographical distribution of P. westermani and P. skrjabini. Additionally, altitude, temperature, and precipitation may influence the distribution of Paragonimus.

Visible Light Induced B-H Bond Insertion Reaction with Diazo Compounds.

A protocol induced by visible light for the direct insertion of α-carbonyl carbenes into the B-H bond of amine-borane adducts has been developed under conditions that are free of metal and photocatalyst. This approach provides a straightforward route to various organoboron compounds from diazo compounds and amine-borane adducts with moderate to good yields. Mechanistic investigations reveal that this photoinduced reaction proceeds through concerted carbene insertion into the B-H bond, and the photoinduced generation of free carbene from α-diazo esters may be the rate-determining step.

Development and validation of a predictive model based on ß-Klotho for head and neck squamous cell carcinoma.

Head and neck epithelial tissue tumors may be identified as head and neck squamous cell carcinoma (HNSC). Numerous malignancies are encouraged by dysregulation of the FGF19-ß-Klotho (KLB) axis in the tumor microenvironment. Using protein databases and RT-qPCR, we examined KLB expression in HNSC. In HNSC, higher KLB expression was linked to longer survival times and better prognoses. Furthermore, variations in drug susceptibility and immunological infiltration were noted according to KLB expression levels. These results underscore the importance of KLB in the course and management of HNSC by indicating that it may function as a possible prognostic marker and influence immunological and therapeutic responses in these individuals. Further study on HNSC is necessary to investigate KLB's potential as a therapeutic target and prognostic indicator.

Enhancing automatic prediction of clinically significant prostate cancer with deep transfer learning 2.5-dimensional segmentation on bi-parametric magnetic resonance imaging (bp-MRI).

Background: The aggressiveness of prostate cancer (PCa) is crucial in determining treatment method. The purpose of this study was to establish a 2.5-dimensional (2.5D) deep transfer learning (DTL) detection model for the automatic detection of clinically significant PCa (csPCa) based on bi-parametric magnetic resonance imaging (bp-MRI). Methods: A total of 231 patients, including 181 with csPCa and 50 with non-clinically significant PCa (non-csPCa), were enrolled. Stratified random sampling was then employed to divide all participants into a training set [185] and a test set [46]. The DTL model was obtained through image acquisition, image segmentation, and model construction. Finally, the diagnostic performance of the 2.5D and 2-dimensional (2D) models in predicting the aggressiveness of PCa was evaluated and compared using receiver operating characteristic (ROC) curves. Results: DTL models based on 2D and 2.5D segmentation were established and validated to assess the aggressiveness of PCa. The results demonstrated that the diagnostic efficiency of the DTL model based on 2.5D was superior to that of the 2D model, regardless of whether in a single or combined sequence. Particularly, the 2.5D combined model outperformed other models in differentiating csPCa from non-csPCa. The area under the curve (AUC) values for the 2.5D combined model in the training and test sets were 0.960 and 0.949, respectively. Furthermore, the T2-weighted imaging (T2WI) model showed superiority over the apparent diffusion coefficient (ADC) model, but was not as effective as the combined model, whether based on 2.5D or 2D. Conclusions: A DTL model based on 2.5D segmentation was developed to automatically evaluate PCa aggressiveness on bp-MRI, improving the diagnostic performance of the 2D model. The results indicated that the continuous information between adjacent layers can enhance the detection rate of lesions and reduce the misjudgment rate based on the DTL model.