Pulmonary microbial spectrum in late-stage SARS-CoV-2 infection: a case series.

Coronavirus disease 2019 (COVID-19), a kind of respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily spreads through the respiratory tract from human to human. Its extensive and rapid spread has led to a global pandemic, causing great harm to human health and economic development all over the world. Current known evidence indicates that SARS-CoV-2 has evolved accumulating multiple mutations, with altered infectivity and viral replication capacity. A better understanding of the complications of COVID-19 and its relationship with underlying diseases is crucial for the prevention and treatment of SARS-CoV-2. This case series reviewed case data of our 4 recent patients with severe or critical COVID-19, including treatment plan, status of pulmonary infection and their microbiology workup with metagenomic next-generation sequencing with bronchoalveolar lavage fluid. This report shed light on the significance of rapid and accurate clinical diagnosis and treatment on COVID-19.

Unraveling the longitudinal relationships between connectedness to nature, depressive symptoms, and learning burnout in adolescents.

INTRODUCTION: Following the conservation of resource theory and natural stress reduction theory, the current study investigated mediated pathways, reverse mediated pathways, and reciprocal pathways between connectedness to nature, depressive symptoms, and adolescent learning burnout via a half-longitudinal analysis, and discussed gender differences in the three models. METHODS: Two waves of data were collected in December 2022 (T1) and June 2023 (T2) for this study. The sample consisted of 1092 Chinese adolescents (52.20% girls, Mage = 13.03, SD = 1.43). Semi-longitudinal analyses were conducted to examine the relationship between connectedness to nature, depressive symptoms, and adolescent academic burnout. RESULTS: The results indicated that connectedness to nature can serve as a positive resource to alleviate the levels of depressive symptoms among adolescents and thereby decrease learning burnout. However, the protective effect of connectedness to nature was smaller, and the decreasing effect of learning burnout on connectedness to nature was stronger than the alleviating effect of connectedness to nature on learning burnout. Additionally, the study found that depressive symptoms and academic burnout have a mutually reinforcing effect over time and that the effects of this interaction are more pronounced in females. CONCLUSIONS: The present study emphasizes the protective role of nature connectedness and the detrimental effects of learning burnout in adolescents.

Natural Environmental Variation Determines Microbial Diversity Patterns in Serofluid Dish, a Traditional Chinese Fermented Vegetable Food.

Serofluid dish is a traditional fermented food that contains rich microbial populations. To gain insight into the environmental variables shaping the microbial diversity patterns, serofluid dish samples were collected from different areas, and 16S rRNA sequencing was performed. Analyses revealed both species and community diversity, including phylotype richness, Shannon index and phylogenetic diversity, were mostly influenced by pH. Additionally, such effects were corroborated by the Mantel test of pairwise UniFrac distances and variable selection of multiple linear regression models. Eventually, correlations between dominant lineages and the pH of serofluid dish other than geographical distance explained a large portion of the changes in microbial composition and diversity. Lactobacillus and related genera, Pediococcus and Acetobacter were largely driven by the variability of pH, and higher richness was observed under moderate pH ranges. Collectively, the results demonstrated that a microbial diversity pattern in serofluid dish is predictable by natural environmental variation and can be better understood through pH conditions.

A Novel Isaindigotone Derivative Displays Better Anti-Proliferation Activities and Induces Apoptosis in Gastric Cancer Cells.

Isaindigotone is an alkaloid containing a pyrrolo-[2,1-b]quinazoline moiety conjugated with a benzylidene group and isolated from the root of Isatis indigotca Fort. However, further anticancer activities of this alkaloid and its derivatives have not been fully explored. In this work, a novel isaindigotone derivative was synthesized and three different gastric cell lines and one human epithelial gastric cell line were used to study the anti-proliferation effects of the novel isaindigotone derivative BLG26. HGC27 cells and AGS cells were used to further explore the potential mechanisms. BLG26 exhibited better anti-proliferation activities in AGS cells with a half-maximal inhibitory concentration (IC50) of 1.45 µM. BLG26 caused mitochondrial membrane potential loss and induced apoptosis in both HGC27 cells and AGS cells by suppressing mitochondrial apoptotic pathway and PI3K/AKT/mTOR axis. Acute toxicity experiment showed that LD50 (median lethal dose) of BLG26 was above 1000.0 mg/kg. This research suggested that BLG26 can be a potential candidate for the treatment of gastric cancer.

Total Synthesis of Geldanamycin.

The total synthesis of geldanamycin, a well-known polyketide that exhibited potent anticancer activity by inhibiting Hsp90, was finished in 26 long linear steps with 2.65% overall yield. High convergency of the synthesis was achieved by the disconnection between C12 and C13 that gives C5-C12 and C13-C21 fragments as major building blocks. The use of an alkynyl ketone as the precursor of the C5-C12 fragment enabled a reagent-controlled establishment of C7 chirality and a highly flexible substituent exchange at C8, making the synthetic route suitable for deep-seated structural modifications on geldanamycin.

Treatment of idiopathic oligozoospermia with recombinant human follicle-stimulating hormone: a prospective, randomized, double-blind, placebo-controlled clinical study in Chinese population.

OBJECTIVE: Follicle-stimulating hormone plays a crucial role in spermatogenesis. The aim of this study was to evaluate the efficacy of treatment with FSH in Chinese infertility population. DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical study. PATIENTS: A total of 354 men affected by idiopathic oligozoospermia from three medical centres. MEASUREMENTS: This study contained three parts: (i) treatment with different doses of rhFSH (50 IU, 100 IU, 200 IU and 300 IU); (ii) the efficacy of rhFSH at different periods (2, 3, 4, 5 months); (iii) FSH treatment in patients with different levels of inhibin B (normal-level group, low-level group and high-level group). Semen parameters were evaluated in all subjects. The patients who had not reached spontaneous pregnancy underwent assisted reproductive techniques. RESULTS: Sperm number was significantly increased after treatment with FSH at doses of at least 200 IU, and the improvement was observed beginning at the third month. The significant improvement in both morphology and forward motility was observed beginning at the fifth month. Moreover, 300 IU rhFSH administration for 5 months could significantly improve the spontaneous pregnancy rate (12/40) and ART pregnancy rate (14/28), while the rates for placebo group were two of twenty-nine and five of twenty-seven, respectively. The seminal parameters (total sperm count, sperm concentration, forward motility and morphology) were significantly improved in the normal- and low-level inhibin B groups, but no significant variation was observed in the high-level group at the end of the study. CONCLUSIONS: The efficacy of FSH treatment was associated with the dose of FSH and duration of treatment, and FSH therapy was more effective in patients with normal level and low level of inhibin B.

Models of sepsis-induced acute kidney injury.

Sepsis-induced acute kidney injury (S-AKI) is one of the most serious life-threatening complications of sepsis. The pathogenesis of S-AKI is complex and there is no effective specific treatment. Therefore, it is crucial to choose suitable preclinical models that are highly similar to human S-AKI to study the pathogenesis and drug treatment. In this review, we summarized recent advances in the development models of S-AKI, providing reference for the reasonable selection of experimental models as basic research and drug development of S-AKI.

Effect of Tea Tree Essential Oil on the Quality, Antioxidant Activity, and Microbiological Safety of Lightly Processed Lily (Lilium brownii var. viridulum) during Storage.

The Lanzhou lily is a regionally distinctive vegetable; the emergence of lightly processed lilies has addressed the inconvenience of consuming fresh lilies. However, the cleaning and impurity removal during the processing of lightly processed lily may strip off its original protective barrier and affect the edible quality. As one of the preservation methods, tea tree essential oil (TTEO) has the characteristics of being green, safe, and efficient preservative properties. This study focused on investigating the effects of different concentrations (25 µL/L, 50 µL/L, and 100 µL/L) of TTEO on the quality and microbiological safety of lightly processed lily. The results showed that compared with the control, appropriate concentrations of TTEO treatment could delay weight loss, improve appearance, firmness, and sensory quality, and maintain microbiological safety with the best effect observed at 50 µL/L. Meanwhile, TTEO treatment induced phenylalanine ammonia-lyase activity, thereby increasing the total phenolic content. Furthermore, TTEO enhanced the superoxide dismutase (SOD) and ascorbate peroxidase (APX) activity, which reduced O2-· production rate and H2O2 content. TTEO inhibited lipoxygenase (LOX) activity, reducing the relative conductivity and malondialdehyde content, thereby delaying lipid peroxidation and quality deterioration. This indicates that TTEO could enhance antioxidant capacity by regulating reactive oxygen species (ROS) metabolism and delay the quality deterioration of lightly processed lily by inhibiting lipid peroxidation.

Nomograms and scoring system for forecasting overall and cancer-specific survival of patients with prostate cancer.

BACKGROUND: Estimated life expectancy is one of the most important factors in determining treatment options for prostate cancer (PCa) patients. However, clinicians have few effective prognostic tools to individually assess survival in patients with PCa. METHODS: We screened 283,252 patients diagnosed with PCa from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015, and randomly divided them into the training and validation groups. We used univariate and multivariate Cox analyses to identify independent prognostic factors and further established nomograms to predict 1-, 3-, 5-, and 10-year overall survival (OS) and cancer-specific survival (CSS) for PCa patients. The prediction performance of nomograms was tested and externally validated by Concordance index (C-index) and receiver operating characteristic (ROC) curve. Calibration curve and decision curve analysis (DCA) were used for internal validation. We further developed PCa prognostic scoring system based on the impact of available variables on survival. RESULTS: The variables age, race, marital status, TNM stage, surgery method, radiotherapy, chemotherapy, PSA value, and Gleason score identified as independent prognostic factors were included in the survival nomograms. The results of training (C-index: OS = 0.776, CSS = 0.889; AUC value: OS = 0.772-0.802, CSS = 0.892-0.936) and external validation (C-index: OS = 0.759, CSS = 0.875) indicated our nomograms had good performance in predicting 1-, 3-, 5-, and 10-year OS and CSS prediction. Internal validation using the calibration curves and DCA curves demonstrated the effectiveness of the prediction models. The prognostic scoring system was more effective than the AJCC staging system in predicting the survival of PCa patients, especially for OS. CONCLUSION: The prognostic nomograms and prognostic scoring system have favorable performance in predicting OS and CSS of PCa patients. These individualized survival prediction tools may contribute to clinical decisions.

Vanillin Derivatives Reverse Fusobacterium nucleatum-Induced Proliferation and Migration of Colorectal Cancer Through E-Cadherin/ß-Catenin Pathway.

Colorectal cancer (CRC) is a common clinical malignant tumor and closely related to intestinal microbiome disorders. Especially, Fusobacterium nucleatum (F. nucleatum) is one of the most prevalent pathogens in CRC. However, its change in CRC patients of Northwest China, an area with a high incidence of gastrointestinal tumors, is unclear, and therapeutic strategies targeting F. nucleatum remain unresolved. Here, fecal samples of healthy people and CRC patients were studied using 16S rRNA sequencing to explore microbial community alterations. Additionally, vanillin derivate (IPM711 and IPM712) intervention by coculture with CRC cells and potential mechanism were investigated. Results showed that intestinal microbial homeostasis was gradually dysregulated, and the abundance of Fusobacterium was higher in CRC patients. Moreover, IPM711 and IPM712 showed better anti-F. nucleatum activity than vanillin by increasing cell membrane permeability and destroying bacterial integrity. In addition, IPM711 and IPM712 could downregulate the expression of E-cadherin and ß-catenin, thus, suppressing the migration of HCT116. Collectively, IPM711 and IPM712 have both anticolorectal cancer and anti-F. nucleatum activities, providing potential natural product drug candidates for microbe-targeted strategies for the treatment of CRC.

Synthesis and biological activity of 1H-imidazo[4,5-f][1,10]phenanthroline as a potential antitumor agent with PI3K/AKT/mTOR signaling.

1H-imidazo[4,5-f][1,10]phenanthroline (IPM713) is a type of tricyclic conjugated rigid planar structure with potential medical applications, but its anticancer activity has not yet been fully studied. In the present research, cells from seven different cancer types were used to study the anticancer effect, and IPM713 was found to inhibit the colorectal cancer cell line HCT116 most significantly, with a half maximal inhibitory concentration (IC50) of 1.7 µM. The mechanisms by which IPM713 exerts anti-colorectal cancer activity were studied. IPM713 blocked the cell cycle in G0/G1 phase and induced apoptosis by suppressing the PI3K/AKT/mTOR axis. In addition, an acute toxicity test showed that the median lethal dose (LD50) was above 5000 mg/kg. The findings of this research suggest that IPM713 can interfere with the PI3K/AKT/mTOR signaling pathway and might be a potential therapeutic candidate for the treatment of colorectal cancer.

Synthesis and anticancer evaluations of novel 1H-imidazole [4,5-f][1,10] phenanthroline derivative for the treatment of colorectal cancer.

1H-imidazole [4,5-f][1,10] phenanthroline is a promising chemical structure for cancer treatment. Herein, we synthesized a novel 1H-imidazole [4,5-f][1,10] phenanthroline derivative named IPM714 and found it exhibited selectively colorectal cancer (CRC) cells inhibitory activities, with half maximal inhibitory concentration (IC50) of 1.74 µM and 2 µM in HCT116 cells and SW480 cells, respectively. The present study is intended to explore the cytotoxicity of IPM714 in cancer cells of various types and its anticancer mechanism in vitro. Cellular functional analyses indicated IPM714 can arrest HCT116 cell cycle in S phase and induce apoptosis in HCT116 and SW480 cells. Western blot and molecular docking showed that IPM714 may suppress PI3K/AKT/mTOR pathway to inhibit cell proliferation and regulate cell cycle as well as apoptosis. This study proved IPM714 to be a promising drug in CRC therapy.

Anti-Gastric Cancer Activity of the Cell-free Culture Supernatant of Serofluid Dish and Lactiplantibacillus plantarum YT013.

Cancer is second only to heart disease as a cause of death, despite improvements in its early diagnosis and precision medicine. Due to the limitations of commonly used anticancer methods such as surgery, radiotherapy and chemotherapy, biological therapy, especially probiotics such as lactic acid bacteria, has received widespread attention. Lactobacillus has been proven to inhibit the proliferation of a variety of cancer cells. In this work, the effects of the cell-free culture supernatant of serofluid dish (CCS1) and the cell-free culture supernatant of Lactiplantibacillus plantarum YT013 (CCS2) isolated from serofluid dish on AGS, HCT116, HepG2 and PANC-1 cells were investigated. Based on the CCK-8 assay, CCS1 and CCS2 were shown to suppress the growth of cancer cells in a concentration-dependent manner. The IC50 values of CCS2 of AGS, HCT116, HepG2 and PANC-1 cells were 346.51 ± 35.28, 1207.69 ± 333.18, 650.94 ± 123.78 and 808.96 ± 126.27 µg/ml, respectively. In addition, the results of fluorescence microscopy showed that CCS2 changed cell morphology and treated with CCS2 (200, 400 and 800 µg/ml) for 48 h, AGS cell apoptosis was quantitatively surveyed by flow cytometry, showing 25.0, 34.1, and 42.6% total apoptotic cells. Moreover, western blotting confirmed that BAX, BAD and Caspase-3/8/9 were significantly upregulated and that BCL-2 was significantly downregulated in AGS cells treated with CCS2. These results indicated that CCS2 might lead to apoptosis via the endogenous mitochondrial apoptotic pathway. In summary, Lactiplantibacillus plantarum YT013 may be considered a good candidate for anticancer therapies.

Differences in survival of prostate cancer Gleason 8-10 disease and the establishment of a new Gleason survival grading system.

BACKGROUND: Although the latest Gleason grading system in 2014 has distinguished between Gleason 3 + 4 and 4 + 3, Gleason 8 and Gleason 9-10 are remained systemically classified. METHODS: A total of 261,125 patients diagnosed with prostate cancer (PCa) were selected between 2005 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. We used propensity score matching to balance clinical variables and then compared overall survival (OS) and cancer-specific survival (CSS) between Gleason score subgroups. We further establish a new Gleason survival grading system based on the hazard ratio (HR) values of each Gleason subgroup. Cox proportional hazards models and Kaplan-Meier curves were used to compare patient survival. RESULTS: Among PCa patients with Gleason score 8 disease, patients with Gleason 5 + 3 had significantly worse OS and CSS than those with Gleason 3 + 5 (OS: HR = 1.26, p = 0.042; CSS: HR = 1.42, p = 0.005) and 4 + 4 (HR = 1.50 for OS and HR = 1.69 for CSS, p < 0.001 for all). PCa patients with Gleason 5 + 3 and Gleason 4 + 5 may have the similar OS and CSS (reference Gleason score <=6, 5 + 3: OS HR = 2.44, CSS HR = 7.63; 4 + 5: OS HR = 2.40, CSS HR = 8.92; p < 0.001 for all). The new Gleason survival grading system reclassified the grades 4 and 5 of the 2014 updated Gleason grading system into three hierarchical grades, which makes the classification of grades more detailed and accurate. CONCLUSION: PCa patients with Gleason 8-10 may have three different survival subgroups, Gleason 3 + 5 and 4 + 4, Gleason 5 + 3 and 4 + 5, and Gleason 5 + 4 and 5 + 5. Our results maximize risk stratification for PCa patients, provide guidance for clinicians to assess their survival and clinical management, and make a recommendation for the next Gleason grading system update.

Prognostic nomograms and Aggtrmmns scoring system for predicting overall survival and cancer-specific survival of patients with kidney cancer.

BACKGROUND: Currently, the prognosis of kidney cancer depends mainly on the pathological grade or tumor stage. Clinicians have few effective tools that can personalize and adequately evaluate the prognosis of kidney cancer patients. METHODS: A total of 70 481 kidney cancer patients were selected from the Surveillance, Epidemiology, and End Results database, among which patients diagnosed in 2005-2011 (n = 42 890) were used to establish nomograms for overall survival (OS) and cancer-specific survival (CSS), and those diagnosed in 2012-2015 (n = 24 591) were used for external validation. Univariate and multivariate Cox analyses were used to determine independent prognostic factors. Concordance index (C-index), receiver operating characteristic curve, and calibration curve were used to evaluate the predictive capacity of the nomograms. We further reduced subgroup classification and used propensity score matching to balance clinical informations, and analyzed the effect of other variables on survival. We established a new kidney cancer prognostic score system based on the effect of all available variables on survival. Cox proportional hazard model and Kaplan-Meier curves were used for survival comparison. RESULTS: Age, gender, marital status, surgery, grade, T stage, and M stage were included as independent risk factors in the nomograms. The favorable area under the curve (AUC) value (for OS, AUC = 0.812-0.858; and for CSS, AUC = 0.890-0.921), internal (for OS, C-index = 0.776; and for CSS, C-index = 0.856), and external (for OS, C-index = 0.814-0.841; and for CSS, C-index = 0.894-0.904) validation indicated that the proposed nomograms could accurately predict 1-, 3-, and 5-year OS and CSS of kidney cancer patients. The Aggtrmmns prognostic scoring system based on age, gender, race, marital status, grade, TNM stage, and surgery of kidney cancer patients could stage patients more explicitly than the AJCC staging system. CONCLUSION: The nomogram and Aggtrmmns scoring system can predict OS and CSS in kidney cancer patients effectively, which may help clinicians personalize prognostic assessments and clinical decisions.

The impact of previous cancer on overall survival of bladder cancer patients and the establishment of nomogram for overall survival prediction.

To investigate the role of previous cancer on overall survival in patients with bladder cancer (BCa) and to establish an effective prognostic tool for individualized overall survival prediction.A total of 78,660 patients diagnosed with BCa between 2000 and 2013 were selected from the Surveillance, Epidemiology, and End Results (SEER) database, among which 8915 patients had a history of other cancers. We compared the overall survival between patients with and without previous cancer after propensity score matching and we further established a nomogram for overall survival prediction.Univariate and multivariate Cox analyses were used to determine independent prognostic factors. The calibration curve and concordance index (C-index) were used to assess the accuracy of the nomogram. Cox proportional hazards models and Kaplan-Meier analysis were used to compare survival outcomes.BCa patients with previous cancer had worse overall survival compared with those without previous cancer (HR = 1.37; 95%CI = 1.32-1.42, P < .001). Cancers in lung prior to BCa had the most adverse impact on overall survival (HR = 2.35; 95%CI = 2.10-2.63; P < .001), and the minimal impact was located in prostate (HR = 1.16; 95%CI = 1.10-1.22; P < .001) for male and in gynecological (HR = 1.15; 95%CI = 1.02-1.30; P = .027) for female. The shorter interval time between 2 cancers and the higher stage of the previous cancer development, the higher risk of death. Age, race, sex, marital status, surgery, radiation, grade, stage, type of previous cancer as the independent prognostic factors were selected into the nomogram. The favorable calibration curve and C-index value (0.784, 95%CI = 0.782-0.786) indicated the nomogram could accurately predict the 1-, 3-, and 5-year overall survival rate of BCa patients.Previous cancer has a negative impact on the overall survival of BCa patients and requires more effective clinical management. The nomogram provides accurate survival prediction for BCa patients and might be helpful for clinical treatment selection and follow-up strategy adjustment.

Human Gut Microbiome-Based Knowledgebase as a Biomarker Screening Tool to Improve the Predicted Probability for Colorectal Cancer.

Colorectal cancer (CRC) is a common clinical malignancy globally ranked as the fourth leading cause of cancer mortality. Some microbes are known to contribute to adenoma-carcinoma transition and possess diagnostic potential. Advances in high-throughput sequencing technology and functional studies have provided significant insights into the landscape of the gut microbiome and the fundamental roles of its components in carcinogenesis. Integration of scattered knowledge is highly beneficial for future progress. In this study, literature review and information extraction were performed, with the aim of integrating the available data resources and facilitating comparative research. A knowledgebase of the human CRC microbiome was compiled to facilitate understanding of diagnosis, and the global signatures of CRC microbes, sample types, algorithms, differential microorganisms and various panels of markers plus their diagnostic performance were evaluated based on statistical and phylogenetic analyses. Additionally, prospects about current changelings and solution strategies were outlined for identifying future research directions. This type of data integration strategy presents an effective platform for inquiry and comparison of relevant information, providing a tool for further study about CRC-related microbes and exploration of factors promoting clinical transformation (available at: http://gsbios.com/index/experimental/dts_ mben?id=1).

IPM712, a vanillin derivative as potential antitumor agents, displays better antitumor activity in colorectal cancers cell lines.

Colorectal cancer (CRC), a major health threat in the world, ranks third in incidence and second in mortality among cancers. Chemotherapy, an important treatment for colorectal cancer, have be limited in the clinic due to the resistance and side effect. Studies have shown that PI3K-related regulatory pathways play a colossal role in colorectal cancer. Therefore, it is a good strategy to find a new drug which works by affecting the PI3K signaling pathway. In this paper, we obtained a new vanillin derivative (IPM712) by modifying the structure of IPM711 and tested its anticancer activity in vitro and toxicity in vivo. Results showed that IPM712 has a better anticancer activity than 5-Fu in HCT116 and SW480 cell lines. Furthermore, IPM712 can inhibit cell proliferation, migration and induce the apoptosis by affecting PI3K-related protein expression. Acute toxicity experiments show that IPM712 has no significant toxicity at therapeutic concentrations. Based on these results, IPM712 is a promising anticancer drug candidate for human colorectal cancer therapy.

Potential application of a knowledgebase of iron metabolism of Acidithiobacillus ferrooxidans as an alternative platform

BACKGROUND: Acidithiobacillus ferrooxidans is a facultative anaerobe that depends on ferrous ion oxidation as well as reduced sulfur oxidation to obtain energy and is widely applied in metallurgy, environmental protection, and soil remediation. With the accumulation of experimental data, metabolic mechanisms, kinetic models, and several databases have been established. However, scattered data are not conducive to understanding A. ferrooxidans that necessitates updated information informed by systems biology. RESULTS: Here, we constructed a knowledgebase of iron metabolism of A. ferrooxidans (KIMAf) system by integrating public databases and reviewing the literature, including the database of bioleaching substrates (DBS), the database of bioleaching metallic ion-related proteins (MIRP), the A. ferrooxidans bioinformation database (Af-info), and the database for dynamics model of bioleaching (DDMB). The DBS and MIRP incorporate common bioleaching substrates and metal ion-related proteins. Af-info and DDMB integrate nucleotide, gene, protein, and kinetic model information. Statistical analysis was performed to elucidate the distribution of isolated A. ferrooxidans strains, evolutionary and metabolic advances, and the development of bioleaching models. CONCLUSIONS: This comprehensive system provides researchers with a platform of available iron metabolism-related resources of A. ferrooxidans and facilitates its application.