Phase separation of RNF214 promotes the progression of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and the expression and function of an uncharacterized protein RNF214 in HCC are still unknown. Phase separation has recently been observed to participate in the progression of HCC. In this study, we investigated the expression, function, and phase separation of RNF214 in HCC. We found that RNF214 was highly expressed in HCC and associated with poor prognosis. RNF214 functioned as an oncogene to promote the proliferation, migration, and metastasis of HCC. Mechanically, RNF214 underwent phase separation, and the coiled-coil (CC) domain of RNF214 mediated its phase separation. Furthermore, the CC domain was necessary for the oncogenic function of RNF214 in HCC. Taken together, our data favored that phase separation of RNF214 promoted the progression of HCC. RNF214 may be a potential biomarker and therapeutic target for HCC.

Black rice diet alleviates colorectal cancer development through modulating tryptophan metabolism and activating AHR pathway.

Consumption of dietary fiber and anthocyanin has been linked to a lower incidence of colorectal cancer (CRC). This study scrutinizes the potential antitumorigenic attributes of a black rice diet (BRD), abundantly rich in dietary fiber and anthocyanin. Our results demonstrate notable antitumorigenic effects in mice on BRD, indicated by a reduction in both the size and number of intestinal tumors and a consequent extension in life span, compared to control diet-fed counterparts. Furthermore, fecal transplants from BRD-fed mice to germ-free mice led to a decrease in colonic cell proliferation, coupled with maintained integrity of the intestinal barrier. The BRD was associated with significant shifts in gut microbiota composition, specifically an augmentation in probiotic strains Bacteroides uniformis and Lactobacillus. Noteworthy changes in gut metabolites were also documented, including the upregulation of indole-3-lactic acid and indole. These metabolites have been identified to stimulate the intestinal aryl hydrocarbon receptor pathway, inhibiting CRC cell proliferation and colorectal tumorigenesis. In summary, these findings propose that a BRD may modulate the progression of intestinal tumors by fostering protective gut microbiota and metabolite profiles. The study accentuates the potential health advantages of whole-grain foods, emphasizing the potential utility of black rice in promoting health.

Highly Efficient Photocatalytic Degradation of Organic Pollutants Using a Polyvinylidene Fluoride/Polyvinylpyrrolidone-Cuprous Oxide Composite Membrane.

Enhancing the efficiency of photocatalysts in the removal of organic pollutants is of vital importance in wastewater treatment. In this work, a set of composite membranes that can be used for efficient removal of the organic dyes, such as methyl orange (MO), methylene blue (MB), and Congo red (CR), were prepared through coblending/electrospinning techniques using polyvinylidene fluoride (PVDF) as the substrate, polyvinylpyrrolidone (PVP) as the dispersing agent and wettability regulator, and cuprous oxide (Cu2O) as the photocatalyst. The results showed that Cu2O particles were well encapsulated in the electrospun PVDF/PVP fibers, and the composite membranes exhibited apparently enhanced hydrophilicity. Furthermore, compared with the pure Cu2O particles, the composite membranes not only showed a higher photocatalytic degradation ratio for MO (93.6%) but also showed a much higher degradation rate (62.4 mg/(mg·h)) in comparison with the other reported Cu2O-based composite photocatalytic materials in the literature. In addition, the membrane sample also had excellent recycling stability, and the retention rate of its removal ability maintained 92.1% after 5 times of recycling. Furthermore, the composite membranes also showed high removal ability toward MB and CR, with photocatalytic degradation ratios of 81.4 and 76.1%, respectively. This work indicates that the prepared PVDF/PVP-Cu2O composite membranes possess promising application prospects in wastewater treatment.

Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella (MMAF) and ICSI outcomes.

Variations in the dynein axonemal heavy chain gene, dynein axonemal heavy chain 6 (DNAH6), lead to multiple morphological abnormalities of the flagella. Recent studies have reported that these deficiencies may result in sperm head deformation. However, whether DNAH6 is also involved in human acrosome biogenesis remains unknown. The purpose of this study was to investigate DNAH6 gene variants and their potential functions in the formation of defective sperm heads and flagella. Whole-exome sequencing was performed on a cohort of 375 patients with asthenoteratozoospermia from the First Affiliated Hospital of Anhui Medical University (Hefei, China). Hematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy were performed to analyze the sperm morphology and ultrastructure. Immunofluorescence staining and Western blot analysis were conducted to examine the effects of genetic variants. We identified three novel deleterious variants in DNAH6 among three unrelated families. The absence of inner dynein arms and radial spokes was observed in the sperm of patients with DNAH6 variants. Additionally, deficiencies in the acrosome, abnormal chromatin compaction, and vacuole-containing sperm heads were observed in these patients with DNAH6 variants. The decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with DNAH6 variants using Western blot. After intracytoplasmic sperm injection (ICSI) treatment, the partner of one patient with a DNAH6 variant achieved successful pregnancy. Overall, novel variants in DNAH6 genes that contribute to defects in the sperm head and flagella were identified, and the findings indicated ICSI as an effective clinical treatment for such patients.

Clinical evaluation of a multitarget fecal immunochemical test-sDNA test for colorectal cancer screening in a high-risk population: a prospective, multicenter clinical study.

Colorectal cancer (CRC) is a major malignancy threatening the health of people in China and screening could be effective for preventing the occurrence and reducing the mortality of CRC. We conducted a multicenter, prospective clinical study which recruited 4,245 high-risk CRC individuals defined as having positive risk-adapted scores or fecal immunochemical test (FIT) results, to evaluate the clinical performance of the multitarget fecal immunochemical and stool DNA (FIT-sDNA) test for CRC screening. Each participant was asked to provide a stool sample prior to bowel preparation, and FIT-sDNA test and FIT were performed independently of colonoscopy. We found that 186 (4.4%) were confirmed to have CRC, and 375 (8.8%) had advanced precancerous neoplasia among the high CRC risk individuals. The sensitivity of detecting CRC for FIT-sDNA test was 91.9% (95% CI, 86.8-95.3), compared with 62.4% (95% CI, 54.9-69.3) for FIT (P < 0.001). The sensitivity for detecting advanced precancerous neoplasia was 63.5% (95% CI, 58.3-68.3) for FIT-sDNA test, compared with 30.9% (95% CI, 26.3-35.6) for FIT (P < 0.001). Multitarget FIT-sDNA test detected more colorectal advanced neoplasia than FIT. Overall, these findings indicated that in areas with limited colonoscopy resources, FIT-sDNA test could be a promising further risk triaging modality to select patients for colonoscopy in CRC screening.

Synergistic driving effects of risk factors on human brucellosis in Datong City, China: A dynamic perspective from spatial heterogeneity.

Brucellosis is a highly contagious zoonotic and systemic infectious disease caused by Brucella, which seriously affects public health and socioeconomic development worldwide. Particularly, in China accumulating eco-environmental changes and agricultural intensification have increased the expansion of human brucellosis (HB) infection. As a traditional animal husbandry area adjacent to Inner Mongolia, Datong City in northwestern China is characterized by a high HB incidence, demonstrating obvious variations in the risk pattern of HB infection in recent years. In this study, we built Bayesian spatiotemporal models to detect the transfer of high-risk clusters of HB occurrence in Datong from 2005 to 2020. Geographically and Temporally Weighted Regression and GeoDetector were employed to investigate the synergistic driving effects of multiple potential risk factors. Results confirmed an evident dynamic expansion of HB from the east to the west and south in Datong. The distribution of HB showed a negative correlation with urbanization level, economic development, population density, temperature, precipitation, and wind speed, while a positive correlation with the normalized difference vegetation index, and grassland/cropland cover areas. Especially, the local animal husbandry and related industries imposed a large influence on the spatiotemporal distribution of HB. This work strengthens the understanding of how HB spatial heterogeneity is driven by environmental factors, through which helpful insights can be provided for decision-makers to formulate and implement disease control strategies and policies for preventing the further spread of HB.

Synchronously Enhanced Removal Ability and Stability of MXene through Biomimetic Modification.

Increasing environmental problems intensify the demand for high-performance environmental purification materials. MXene is a typical transition-metal carbide/nitride material with a two-dimensional geometric feature and a good deal of functional groups, and it is considered as an efficient adsorbent for removing pollutants from wastewater. However, the easy oxidation and relatively low adsorption capacity greatly restrict its application. In this study, the MXene/polydopamine (PDA) composite particles were fabricated through the biomimetic modification method of inducing the self-polymerization of dopamine in an MXene aqueous solution. Microstructure characterizations demonstrate that PDA facilitates the exfoliation of MXene. Adsorption measurements show that MXene and PDA exhibit an apparent synergistic effect in removing chromium hexavalent Cr(VI) from aqueous solution, and more PDA content leads to a larger synergistic effect. Consequently, the composite particles exhibit an ultrahigh adsorption capacity (862.3 mg/g). Specifically, even if the composite particles were stored in aqueous solution for 2 months, they still exhibit high adsorption ability with only a 3.3% loss in adsorption capacity, indirectly confirming the enhanced stability of MXene induced by PDA. Furthermore, the composite particles also show reduction ability to Cr(VI) and about 54.3% Cr(VI) can be reduced to harmless chromium trivalent Cr(III). This study provides a new method for the preparation of MXene-based adsorbents with excellent adsorption capacity and high stability, which has broad application prospects in the field of wastewater treatment.

Biomimetic Polylactic Acid Electrospun Fibers Grafted with Polyethyleneimine for Highly Efficient Methyl Orange and Cr(VI) Removal.

The rapid growth of industrialization has resulted in the release of large quantities of pollutants into the environment, especially dyes and heavy metals, which are environmentally hazardous for humans and animals. It is considered as the most promising and environmentally friendly route to develop green materials by using the green modification method, which has no negative impact on the environment. In this work, the green material of polylactic acid (PLA) was used as the substrate material, and a novel modification method of polydopamine (PDA)-assisted polyethyleneimine (PEI) grafting was developed. The electrospun PLA fibers are mainly composed of stereocomplex crystallites, which were achieved via the electrospinning of poly(l-lactic acid) and poly(d-lactic acid). The water-soluble PEI was grafted onto the PDA-modified PLA fibers through the glutaraldehyde-assisted cross-linking reaction. The prepared composite fibers can be degraded, which is environmentally friendly and meets the requirements of sustainable development. The potential application of such PLA composite fibers in wastewater treatment was intensively evaluated. The results show that at appropriate fabrication conditions (PDA concentration of 3 g·L-1 and a PEI molecular weight of 70,000 g·mol-1), the composite fibers exhibit the maximum adsorption capacities of 612 and 398.41 mg·g-1 for methyl orange (MO) and hexavalent chromium [Cr(VI)], respectively. Simultaneously, about 64.79% of Cr(VI) adsorbed on the composite fibers was reduced to Cr(III). The above results show that the PLA composite fibers have a good development prospect in the field of wastewater treatment.

Differential microbial composition in parasitic vs. questing ticks based on 16S next-generation sequencing.

Introduction: As tick-borne diseases rise to become the second most prevalent arthropod-transmitted disease globally, the increasing investigations focus on ticks correspondingly. Factors contributed to this increase include anthropogenic influences, changes in vertebrate faunal composition, social-recreational shifts, and climatic variation. Employing the 16S gene sequence method in next-generation sequencing (NGS) allows comprehensive pathogen identification in samples, facilitating the development of refined approaches to tick research omnidirectionally. Methods: In our survey, we compared the microbial richness and biological diversity of ticks in Wuwei City, Gansu province, differentiating between questing ticks found in grass and parasitic ticks collected from sheep based on 16S NGS method. Results: The results show Rickettsia, Coxiella, and Francisella were detected in all 50 Dermacentor nuttalli samples, suggesting that the co-infection may be linked to specific symbiotic bacteria in ticks. Our findings reveal significant differences in the composition and diversity of microorganisms, with the Friedmanniella and Bordetella genera existing more prevalent in parasitic ticks than in questing ticks (p < 0.05). Additionally, the network analysis demonstrates that the interactions among bacterial genera can be either promotive or inhibitive in ticks exhibiting different lifestyles with the correlation index |r| > 0.6. For instance, Francisella restrains the development of 10 other bacteria in parasitic ticks, whereas Phyllobacterium and Arthrobacter enhance colonization across all tick species. Discussion: By leveraging NGS techniques, our study reveals a high degree of species and phylogenetic diversity within the tick microbiome. It further highlights the potential to investigate the interplay between bacterial genera in both parasitic and questing ticks residing in identical habitat environments.

Latitudinal and longitudinal regulation of tissue macrophages in inflammatory diseases.

Macrophages are dominant innate immune cells. They demonstrate remarkable heterogeneity and plasticity that are essential for homeostasis and host defense. The heterogeneity of tissue macrophages is shaped by the ontogeny, tissue factors, and environmental signals, a pattern in a tissue-associated latitudinal manner. At the same time, macrophages have long been considered as mainly plastic cells. These cells respond to stimulation quickly and in a stimulus-specific way by utilizing a longitudinal cascaded activation, including coordination of signal transducer, epigenetic elements, and transcription factors, conclusively determine the macrophage phenotypes and functions. With the development of cutting-edge technologies, such as fate-mapping, single-cell transcriptomics, ipsc platform, nanotherapeutic materials, etc., our understanding of macrophage biology and the roles in the pathogenesis of diseases is much advanced. This review summarizes recent progress on the latitudinal and longitudinal regulation of tissue macrophages in inflammatory diseases. The latitudinal regulation covers the tissue macrophage origins, tissue factors, and environmental signals, reflecting the macrophage heterogeneity. The longitudinal regulation focuses on how multiple factors shape the phenotypes and functions of macrophage subsets to gain plasticity in inflammatory diseases (i.e., inflammatory bowel disease). In addition, how to target macrophages as a potential therapeutic approach and cutting edge-technologies for tissue macrophage study are also discussed in this review.

Competitive and sequence reactions of typical hydrocarbon molecules in diesel fraction hydrocracking - a theoretical study by DFT calculations.

The molecular structures of hydrocarbon molecules determine the competitive and sequence reactions in the diesel hydrocracking process. In this study, the hydrocracking reactions of typical hydrocarbons with various saturation degrees and molecular weights in diesel fractions synergistically catalyzed by the Ni-Mo-S nanocluster and Al-Si FAU zeolite are investigated. The results show that the two major rate-controlling steps in saturated hydrocarbon hydrocracking are dehydrogenation on the Ni-Mo-S active sites and the cracking of the C-C bonds on the FAU zeolite acid center. Moreover, the major rate-controlling step in cracking the cycloalkyl aromatic hydrocarbons is the protonation of the aromatic ring. Moreover, the aromatic hydrocarbons presented an apparent advantage in competitive adsorption on the Ni-Mo-S active sites, whereas hydrocarbons with higher molecular weights demonstrated a moderate adsorption advantage on both Ni-Mo-S active sites and FAU zeolite acid centers.

Zusammenhang zwischen Vitiligo und wichtigen Komponenten des metabolischen Syndroms: eine systematische Übersicht und Metaanalyse.

HINTERGRUND UND ZIELE: Ziel dieser Studie war die Untersuchung des Zusammenhangs zwischen Vitiligo und dem metabolischen Syndrom (MetS) sowie dessen relevanten Komponenten. MATERIAL UND METHODEN: Die Datenbanken PubMed, Web of Science, Cochrane Library und Embase wurden von deren Beginn bis zum 30. März 2021 nach relevanten Studien durchsucht. Querschnitts- und Fall-Kontroll-Studien, die entweder die Prävalenz oder die Odds-Ratio [OR] des MetS oder seiner Komponenten bei Vitiligo-Patienten berichteten, wurden eingeschlossen. Die Daten wurden entsprechend der Heterogenität entweder mit einem Zufallseffektmodell oder einem Modell mit festen Effekten gepoolt. ERGEBNISSE: Es wurden 30 Studien mit insgesamt 28.325 Vitiligo-Patienten eingeschlossen. Signifikante Zusammenhänge wurden zwischen Vitiligo und Diabetes mellitus (gepoolte OR, 3,30; 95 %-Konfidenzintervall [KI], 2,10-5,17) sowie zwischen Vitiligo und Adipositas (gepoolte OR, 2,08; 95 %-KI, 1,40-3,11) ermittelt. Die Gesamtprävalenz der Hypertonie bei Patienten mit Vitiligo betrug 19,0 % (95 %-KI, 2,0 %-36,0 %). SCHLUSSFOLGERUNGEN: Unserer Ergebnisse lassen auf einen Zusammenhang zwischen Vitiligo und Diabetes mellitus sowie Hypertonie schließen. Dermatologen wird empfohlen diese Zusammenhänge zu berücksichtigen, um potenzielle Begleiterkrankungen bei Vitiligo-Patienten zeitnah zu identifizieren. Zudem wird Vitiligo-Patienten empfohlen, Parameter wie BMI, Blutzuckerspiegel und Blutdruck zu überwachen und bei auffälligen Veränderungen dieser Parameter unverzüglich einen Spezialisten zu konsultieren.

Effectiveness and Safety of Baidu Jieduan Granules for COVID-19: A Retrospective Observational Multicenter Study.

OBJECTIVE: To evaluate the effectiveness and safety of Baidu Jieduan Granules (BDJDG) to treat common type coronavirus disease 2019 (COVID-19). METHODS: This multicenter, retrospective, and observational clinical trial included 230 common COVID-19 patients in Leishenshan, Huangshi, and Laohekou Hospitals in Wuhan from January 21 to March 26, 2020. The included patients were further divided into two subgroups according to the use of supplemental oxygen, mild and moderate groups. During the first 14 d of hospitalization, all patients were administered BDJDG combined with conventional Western medicine, and observed for continuous 28 d. Primary outcomes were disease progression rate and discharge rate. Secondary outcomes included negative conversion time of nucleic acid, hospitalization duration, clinical symptom subsidence time, and symptom regression rate. RESULTS: A total of 230 common COVID-19 patients were analyzed (138 in moderate group and 92 in mild group). By day 28, the disease progression rate was 4.3% and the discharge rate was 95.7%. All mild cases recovered and were discharged from hospital. The median negative conversion time of nucleic acid of all 230 COVID-19 patients was 12 d [inter-quartile range (IQR) 3.5-17], the median hospitalization duration was 15 d (IQR 12-20). The median time to fever, cough, and fatigue recovery was 4 d (IQR 2-6), 8 d (IQR 5-12), and 8 d (IQR 5-11). The recovery rate of fever, cough, and fatigue was 94.6%, 90.5%, and 93.5%. The median time to clinical improvement was 12 d (IQR 10-17). Compared with the baseline, total leukocyte counts, neutrophil counts, lymphocyte counts, and platelet counts were increased significantly on days 7 and 14 (P<0.01). C-reactive protein markedly increased on day 3 and significantly decreased on days 7 and 14 (P<0.01). No serious adverse events occurred during treatment. CONCLUSION: BDJDG may be effective and safe for treatment of common type COVID-19. (Registration No. ChiCTR2000030836).

Association between vitiligo and relevant components of metabolic syndrome: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: This study aimed to investigate the association of vitiligo with metabolic syndrome (MetS) and its relevant components. MATERIAL AND METHODS: We searched PubMed, Web of Science, Cochrane Library and Embase databases from inception to March 30, 2021, for relevant studies. Cross-sectional and case-control studies that reported either the prevalence or odds ratio [OR] of MetS or its components in vitiligo patients were included. Data were pooled using either random-effects model or fixed-effects model according to the heterogeneity. RESULTS: Thirty studies with a total of 28,325 vitiligo patients were included. Significant associations were found between vitiligo and diabetes mellitus (pooled OR, 3.30; 95 % confidence interval [CI], 2.10-5.17) and between vitiligo and obesity (pooled OR, 2.08; 95 % CI, 1.40-3.11). The overall prevalence of hypertension in the patients with vitiligo was 19.0 % (95 % CI, 2.0 %-36.0 %). CONCLUSIONS: Our findings suggest the association of vitiligo with diabetes mellitus, obesity, and hypertension. It is recommended for dermatologists to take these associations into account so as to identify potential comorbidities promptly in vitiligo patients. Additionally, vitiligo patients are advised to monitor the indexes including BMI, blood glucose, and blood pressure levels and the consultation with specialists is necessary upon abnormal changes of these indexes.

Analyzing the Spatiotemporal Distribution and Characteristics of Liver Cirrhosis in Hospitalized Patients in Wuwei, Gansu Province During 1995-2016: A Long-Term Retrospective Study.

Objectives: This was a long-term retrospective study, aiming to understand the temporal and spatial trend of cirrhosis in Wuwei from 1995 to 2016, explore its spatio-temporal aggregation, and find out the high incidence areas. To provide theoretical basis for the formulation of comprehensive prevention and treatment strategy of cirrhosis in Wuwei. Methods: Herein, we extracted data of cirrhosis patients who were treated in 12 sentinel hospitals in Wuwei from their medical records. We used SAS and Joinpoint Regression Program for data analysis, SaTScan 9.4 software for clustering area detection, and ArcGIS 10.2 software for geographical distribution mapping. Results: Among 3308 patients with liver cirrhosis (average age, 55.34 years) included in this study, 15.9% were aged 50-54 years. The majority were men (2716, 65.8%), with a sex ratio of 1.92:1 and peasants by occupation (1369, 60.3%). The basic social medical insurance system covered the healthcare costs of 1271 patients (63%). A Joinpoint regression analysis done for 1995-2016 revealed an increase in the standardized cirrhosis rate [average annual percent change (AAPC) = 16.7% (95% CI, 10.2-23.5%)] with three joinpoints in 2010, 2013, and 2016. The annual percent change (APC) from 1995 to 2010 was 11.13% (95% CI: 6.5-16.0), and APC from 2010 to 2013 was 66.48% (95% CI:16.0-138.9); conversely, from 2013 to 2016, APC was 4.4% (95% CI, -7.5-17.8%). Hongshagang Town showed the highest average incidence. Each township showed a gradual increase in the incidence after 2010. The results revealed that in each township, liver cirrhosis incidence had some spatial aggregation and was nonrandom. Four liver cirrhosis clusters were noted in 75 townships in Wuwei. Data were gathered from 2011 to 2016. Conclusions: From 1995 to 2016, the incidence of cirrhosis in Wuwei still showed an increasing trend, but the growth rate slowed down since 2013. In Wuwei, the rate of standardization of cirrhosis in female patients increased steadily and faster than in male patients. It is necessary to strengthen the diagnosis, treatment, prevention, and control measures of cirrhosis-related diseases. The results of spatial scanning, basic spatial distribution, aggregation time, and time trend analysis were consistent.

Chitosan-assisted MOFs dispersion via covalent bonding interaction toward highly efficient removal of heavy metal ions from wastewater.

Metal organic frameworks (MOFs) have been considered to be robust adsorbent for the removing heavy metal ions from wastewater due to their unique properties such as large active sites, high specific surface area and high porosity, etc., however, their practical engineering application faces the problem of serious agglomeration. In this work, a new strategy of chitosan (CS) assisting MOF dispersion was proposed to develop the new generation of MOF-based adsorbents, namely, CS grafted UiO-66-NH2 composite materials (CGUNCM). The UiO-66-NH2 was selected and it was grafted onto the main chains of CS through covalent bonding interaction with the aid of glutaraldehyde, which was totally different from the common method that grafting molecular chains on the surface of MOFs resulting in the dramatic reduction of active adsorption sites. The results show that grafting MOFs onto CS main chains not only greatly improves the dispersion of MOFs but also reserves the morphology of MOFs as much as possible. The adsorption performances toward Cu(II) and Pb(II) were intensively studied by varying adsorbate concentration, ionic strength, the contact time, adsorption temperature and pH value of solution. The results show that the composite adsorbent exhibits high adsorption efficiency and the adsorption equilibrium can be reached within 45 min, and the maximum adsorption capacity toward Cu(II) and Pb(II) achieve 364.96 mg/g and 555.56 mg/g, respectively. Furthermore, the composite adsorbent shows good reusability. This work provides a new method of fabricating the MOF-based adsorbent and paves the way for the practical application of such adsorbents in wastewater treatment.

STAT3 as a target for sensitizing prostate cancer cells to irradiation.

Radioresistance of prostate cancer (PCa) is a major factor leading to local failure of radiotherapy. STAT3 is an oncogenic protein that was recently found to be activated in PCa tumors. This study aimed to investigate the radiosensitization effect of targeting STAT3 in PCa tumors. Here, the radiosensitization effect of STAT3 blockade was investigated by clonogenic assay, flow cytometry and western blot analysis in human PCa cells in vitro and in vivo. We demonstrated that STAT3 blockade with a STAT3 inhibitor or siRNA increased the radiosensitivity of PCa cells and that radiation together with STAT3 blockade induced more apoptosis and double-strand breaks (DSBs) than radiation alone in LNCaP cells. In addition, radiation induced STAT3 activation and survivin expression in PCa cells, which was inhibited by STAT3 blockade. Transfection with survivin cDNA attenuated the radiosensitization effect of STAT3 blockade. These effects were further confirmed by in vivo studies, which showed that the STAT3 inhibitor enhanced the treatment efficacy of radiation on LNCaP xenografts with decreased STAT3 activation and survivin expression. These findings suggest that STAT3 blockade radiosensitizes PCa cells through regulation of survivin. Thus, our study has revealed STAT3 as a potential sensitizer for irradiation in PCa cells. Its clinical application as an adjuvant in radiotherapy of PCa should be explored in the future.

Alterations in the Composition of Intestinal DNA Virome in Patients With COVID-19.

Patients with Coronavirus Disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection mainly present with respiratory issues and related symptoms, in addition to significantly affected digestive system, especially the intestinal tract. While several studies have shown changes in the intestinal flora of patients with COVID-19, not much information is available on the gut virome of such patients. In this study, we used the viromescan software on the latest gut virome database to analyze the intestinal DNA virome composition of 15 patients with COVID-19 and investigated the characteristic alternations, particularly of the intestinal DNA virome to further explore the influence of COVID-19 on the human gut. The DNA viruses in the gut of patients with COVID-19 were mainly crAss-like phages (35.48%), Myoviridae (20.91%), and Siphoviridae (20.43%) family of viruses. Compared with healthy controls, the gut virome composition of patients with COVID-19 changed significantly, especially the crAss-like phages family, from the first time of hospital admission. A potential correlation is also indicated between the change in virome and bacteriome (like Tectiviridae and Bacteroidaceae). The abundance of the viral and bacterial population was also analyzed through continuous sample collection from the gut of patients hospitalized due to COVID-19. The gut virome is indeed affected by the SARS-CoV-2 infection, and along with gut bacteriome, it may play an important role in the disease progression of COVID-19. These conclusions would be helpful in understanding the gut-related response and contribute to the treatment and prevention strategies of COVID-19.

Impact of intravenous dexmedetomidine on postoperative bowel movement recovery after laparoscopic nephrectomy: A consort-prospective, randomized, controlled trial.

BACKGROUND: Postoperative ileus is a frequent postoperative complication, especially after abdominal surgery. Sympathetic excitation is the primary factor for postoperative ileus. Sympathetic activation becomes increased by surgical stress, postoperative pain, and inflammation. Dexmedetomidine (DEX) can inhibit sympathetic nerve activity, inflammation, and pain. AIM: To observe whether DEX promotes bowel movements in patients after laparoscopic nephrectomy. METHODS: One hundred and twenty patients undergoing laparoscopic nephrectomy were assigned to three groups: C (normal saline infusion), D1 (DEX 0.02 µg/kg/h), and D2 (DEX 0.04 µg/kg/h). The primary outcomes were the recorded times to first flatus, defecation, and eating after surgery. The secondary outcomes were postoperative pain, assessed using the numerical rating scale (NRS), adverse effects, and the duration of the postoperative hospital stay. RESULTS: The times to first flatus, defecation, and eating in groups D1 and D2 were significantly shorter than those in group C (P < 0.01). The NRS scores at 8 h and 24 h after surgery were significantly lower in groups D1 and D2 than in group C (P < 0.05). No adverse effects were observed (P > 0.05). CONCLUSION: Postoperative infusion of DEX at 0.04 µg/kg/h facilitates bowel movements in patients undergoing laparoscopic nephrectomy.

Inflammation-Immunity-Nutrition Score: A Novel Prognostic Score for Patients with Resectable Colorectal Cancer.

PURPOSE: This study was designed to investigate the prognostic value of the combination of high-sensitivity C-reactive protein, lymphocyte, and albumin in patients with resectable colorectal cancer. PATIENTS AND METHODS: Seven-hundred-and-nineteen patients who underwent colorectal cancer resection in Hubei Cancer Hospital were included. Inflammation-Immunity-Nutrition score (0-6) was constructed based on preoperative high-sensitivity C-reactive protein, lymphocyte, and albumin. Time-dependent receiver operating characteristic curve, decision curve, Kaplan-Meier survival curve, Cox regression, and C-index were conducted to detect the prognostic values of inflammation-immunity-nutrition score. The prognostic values of inflammation-immunity-nutrition score in different subgroups by sex, location of tumor, pathologic stage, and KRAS mutation were also explored. The prognostic performance of inflammation-immunity-nutrition score was further compared with that of other traditional prognostic indicators. RESULTS: The median follow-up time was 40 months. High inflammation-immunity-nutrition score (>2 scores) presented worse survival, with the adjusted hazard ratios (95% confidence intervals) of 3.106 (2.202-4.380) for overall survival and 2.105 (1.604-2.764) for disease-free survival. Besides, the associations of high inflammation-immunity-nutrition score with overall survival were even stronger in cases with wild type KRAS, with the adjusted hazard ratios (95% confidence intervals) of 4.018 (2.355-6.854). Considering the AUCs, C-indices, and hazard ratios estimates, inflammation-immunity-nutrition score presented better prognostic performance than high-sensitivity modified Glasgow prognostic score, high-sensitivity C-reactive protein to albumin ratio, prognostic nutrition index, carcinoembryonic antigen, and carbohydrate antigen 19-9 for overall survival. CONCLUSION: Inflammation-immunity-nutrition score might serve as a powerful prognostic score in patients with colorectal cancer for overall survival, particularly in patients with wild type KRAS.