Use of Lentivirus-Based Method for Establishing TK6 Human Cell Lines Expressing Cytochrome P450 and its Applications in Genotoxicity Testing.

The human lymphoblastoid cell line TK6 stands out as the most widely employed human cell line in genotoxicity testing, as recommended by various testing guidelines for in vitro assessments. Nevertheless, like many testing cell lines, TK6 lacks functional phase I drug-metabolizing enzymes crucial for chemical genotoxicity evaluations. This protocol introduces a lentivirus-based methodology for establishing a panel of TK6-derived cell lines, each expressing one of 14 cytochrome P450s (CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, and CYP3A7). The utilization of a lentiviral expression system ensures stable transduction, offering notable advantages such as sustained transgene expression, high transduction efficiency, positive selection feasibility, and user-friendly application. Additionally, we present a detailed procedure for validating the enhanced expression of each CYP in the established cell lines through real-time PCR, western blotting, and mass spectrometry analysis. Lastly, we exemplify the application of these CYP-expressing TK6 cell lines in genotoxicity testing, employing a flow-cytometry-based in vitro micronucleus test. Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Basic Protocol 1: Lentivirus production and transduction for TK6 cells Support Protocol: Selecting a single clone of CYP-expressing TK6 cells Basic Protocol 2: Validation of CYP expression in TK6 cell lines Basic Protocol 3: Application of transduced cell lines in flow-cytometry-based micronucleus assay.

Transcriptome analysis of long non-coding RNA and mRNA Profiles in VSV-infected BHK-21 Cells.

BACKGROUND: Vesicular stomatitis virus (VSV) is a typical non-segmented negative-sense RNA virus of the genus Vesiculovirus in the family Rhabdoviridae. VSV can infect a wide range of animals, including humans, with oral blister epithelial lesions. VSV is an excellent model virus with a wide range of applications as a molecular tool, a vaccine vector, and an oncolytic vector. To further understand the interaction between VSV and host cells and to provide a theoretical basis for the application prospects of VSV, we analyzed the expression of host differentially expressed genes (DEGs) during VSV infection using RNA-Seq. RESULTS: Our analyses found a total of 1015 differentially expressed mRNAs and 161 differentially expressed LncRNAs in BHK-21 cells infected with VSV for 24 h compared with controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment showed that the differentially expressed lncRNAs and their target genes were mainly concentrated in pathways related to apoptosis, cancer, disease, and immune system activation, including the TNF, P53, MAPK, and NF-kappaB signaling pathways. The differentially expressed lncRNA can modulate immune processes by regulating genes involved in these signaling transmissions. Ten randomly selected DEGs, namely, Il12rb2, F2, Masp2, Mcl1, FGF18, Ripk1, Fas, BMF, POLK, and JAG1, were validated using RT-qPCR. As predicted through RNA-Seq analysis, these DEGs underwent either up- or downregulation, suggesting that they may play key regulatory roles in the pathways mentioned previously. CONCLUSIONS: Our study showed that VSV infection alters the host metabolic network and activates immune-related pathways, such as MAPK and TNF. The above findings provide unique insights for further study of the mechanism of VSV-host interactions and, more importantly, provide a theoretical basis for VSV as an excellent vaccine carrier.

Evaluation of a microphysiological human placental barrier model for studying placental drug transfer.

Understanding drug transport across the placental barrier is important for assessing the potential fetal drug toxicity and birth defect risks. Current in vivo and in vitro models have structural and functional limitations in evaluating placental drug transfer and toxicity. Microphysiological systems (MPSs) offer more accurate and relevant physiological models of human tissues and organs on a miniature scale for drug development and toxicology testing. MPSs for the placental barrier have been recently explored to study placental drug transfer. We utilized a multilayered hydrogel membrane-based microphysiological model composed of human placental epithelial and endothelial cells to replicate the key structure and function of the human placental barrier. A macroscale human placental barrier model was created using a transwell to compare the results with the microphysiological model. Placental barrier models were characterized by assessing monolayer formation, intercellular junctions, barrier permeability, and their structural integrity. Three small-molecule drugs (glyburide, rifaximin, and caffeine) that are prescribed or taken during pregnancy were studied for their placental transfer. The results showed that all three drugs crossed the placental barrier, with transfer rates in the following order: glyburide (molecular weight, MW = 494 Da) < rifaximin (MW = 785.9 Da) < caffeine (MW = 194.19 Da). Using non-compartmental analysis, we estimated human pharmacokinetic characteristics based on in vitro data from both MPS and transwell models. While further research is needed, our findings suggest that MPS holds potential as an in vitro tool for studying placental drug transfer and predicting fetal exposure, offering insights into pharmacokinetics.

Risk factors of positive depression screening during the third trimester of pregnancy in a Chinese tertiary hospital: a cross-sectional study.

OBJECTIVE: Pregnant women experience enormous psychological pressure, particularly during the late trimester. Symptoms of depression in late pregnancy may persist postpartum, increasing the incidence of postpartum depression. This study is aimed to investigate the factors influencing depressive symptoms among pregnant women in their third trimester at a Chinese tertiary hospital and provide information for effective intervention. METHODS: Pregnant women in their third trimester who visited the Ningbo Women and Children's Hospital between January 1, 2020 and June 30, 2022 participated in this study. A score of ≥ 13 on the Edinburgh Postnatal Depression Scale (EPDS) was considered as positive for depressive symptom. Potential influencing factors were examined by using an online questionnaire and analyzed using multivariate logistic regression. RESULTS: A total of 1196 participants were recruited. The mean EPDS score was 7.12 ± 4.22. The positive screening rate for depressive symptom was 9.9%. Univariate analysis showed that living with partner, annual family income, planned pregnancy, sleep quality, and partner's drinking habits were related to positive screening for depression(P < 0.05). Furthermore, multivariate logistic regression analysis showed that living away from the partner (odds ratio [OR]: 2.054, 95% confidence interval [CI]: 1.094-3.696, P = 0.02), annual family income < 150,000 Chinese Yuan (CNY; OR: 1.762, 95% CI: 1.170-2.678, P = 0.007), poor sleep quality (OR: 4.123, 95% CI: 2.764-6.163, P < 0.001), and partner's frequent drinking habit (OR: 2.227, 95% CI: 1.129-4.323, P = 0.019) were independent influencing factors for positive depression screening (P < 0.05). CONCLUSION: Family's economic condition, sleep quality, living with partner, and partner's drinking habits were related to positive depression screening in late pregnancy. Pregnant women with these risk factors should be given more attention and supported to avoid developing depression.

Augmenting L3MBTL2-induced condensates suppresses tumor growth in osteosarcoma.

Osteosarcoma is a highly aggressive cancer and lacks effective therapeutic targets. We found that L3MBTL2 acts as a tumor suppressor by transcriptionally repressing IFIT2 in osteosarcoma. L3MBTL2 recruits the components of Polycomb repressive complex 1.6 to form condensates via both Pho-binding pockets and polybasic regions within carboxyl-terminal intrinsically disordered regions; the L3MBTL2-induced condensates are required for its tumor suppression. Multi-monoubiquitination of L3MBTL2 by UBE2O results in its proteasomal degradation, and the UBE2O/L3MBTL2 axis was crucial for osteosarcoma growth. There is a reverse correlation between L3MBTL2 and UBE2O in osteosarcoma tissues, and higher UBE2O and lower L3MBTL2 are associated with poorer prognosis in osteosarcoma. Pharmacological blockage of UBE2O by arsenic trioxide can enhance L3MBTL2-induced condensates and consequently suppress osteosarcoma growth. Our findings unveil a crucial biological function of L3MBTL2-induced condensates in mediating tumor suppression, proposing the UBE2O-L3MBTL2 axis as a potential cancer therapeutic target in osteosarcoma.

The involvement of hepatic cytochrome P450s in the cytotoxicity of lapatinib.

Lapatinib, an oral tyrosine kinase inhibitor used as a first-line treatment for HER2-positive breast cancer, has been reported to be associated with hepatotoxicity; however, the underlying mechanisms remain unclear. In this study, we report that lapatinib causes cytotoxicity in multiple types of hepatic cells, including primary human hepatocytes, HepaRG cells, and HepG2 cells. A 24-h treatment with lapatinib induced cell cycle disturbances, apoptosis, and DNA damage, and decreased the protein levels of topoisomerase in HepG2 cells. We investigated the role of cytochrome P450 (CYP)-mediated metabolism in lapatinib-induced cytotoxicity using our previously established HepG2 cell lines, which express each of 14 CYPs (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, and 3A7). We demonstrate that lapatinib is metabolized by CYP1A1, 3A4, 3A5, and 3A7. Among these, lapatinib-induced cytotoxicity and DNA damage were attenuated in cells overexpressing CYP3A5 or 3A7. Additionally, we measured the production of three primary metabolites of lapatinib (O-dealkylated lapatinib, N-dealkylated lapatinib, and N-hydroxy lapatinib) in CYP1A1-, 3A4-, 3A5-, and 3A7-overexpressing HepG2 cells. We compared the cytotoxicity of lapatinib and its 3 metabolites in primary human hepatocytes, HepaRG cells, and HepG2 cells and demonstrated that N-dealkylated lapatinib is more toxic than the parent drug and the other metabolites. Taken together, our results indicate that lapatinib-induced cytotoxicity involves multiple mechanisms, such as apoptosis and DNA damage; that N-dealkylated lapatinib is a toxic metabolite contributing to the toxic effect of lapatinib; and that CYP3A5- and 3A7-mediated metabolism plays a role in attenuating the cytotoxicity of lapatinib.

Cooled infrared coaxial four-mirror system design with a low F-number.

A low F-number and 100% cold stop efficiency are beneficial for improving the performance of optical systems and have a wide range of applications in various thermal imaging scenarios. The cooled infrared coaxial four-mirror system can meet these two requirements, improve system integration, and reduce adjustment costs and difficulties. However, the secondary obstruction caused by the central hole of the third mirror will generate potential stray light. A structure model is proposed in which the primary mirror and the quaternary mirror are processed on the same mirror blank. In this model, a method is given to calculate system parameters using the obstruction ratio and magnification of each mirror. To evaluate the performance of the method, two design examples with different F-numbers (1.4, 1.0) were constructed. The influence of initial structural constraints on the exit pupil position and secondary obstruction was analyzed based on the design objectives of the examples. The aberrations were optimized by targeting the spot. In the optimization process, the incident coordinates and directions of the restricted edge field rays in the tertiary mirror and the quaternary mirror were limited to achieve control of the obstruction caused by the holes in the center of the mirrors. In the results, the RMS spot radius of the two design examples is smaller than the Airy disk radius, and the axial beam wavefront deviation RMS values are 0.026λ and 0.024λ, respectively. Moreover, the obstruction caused by the central holes of the mirrors is controlled within the given field of view. The results show that the proposed model and method can be used to design a low F-number cooled infrared coaxial four-mirror system and have good application prospects.

Real-time and accurate estimation of surgical hemoglobin loss using deep learning-based medical sponges image analysis.

Real-time and accurate estimation of surgical hemoglobin (Hb) loss is essential for fluid resuscitation management and evaluation of surgical techniques. In this study, we aimed to explore a novel surgical Hb loss estimation method using deep learning-based medical sponges image analysis. Whole blood samples of pre-measured Hb concentration were collected, and normal saline was added to simulate varying levels of Hb concentration. These blood samples were distributed across blank medical sponges to generate blood-soaked sponges. Eight hundred fifty-one blood-soaked sponges representing a wide range of blood dilutions were randomly divided 7:3 into a training group (n = 595) and a testing group (n = 256). A deep learning model based on the YOLOv5 network was used as the target region extraction and detection, and the three models (Feature extraction technology, ResNet-50, and SE-ResNet50) were trained to predict surgical Hb loss. Mean absolute error (MAE), mean absolute percentage error (MAPE), coefficient (R2) value, and the Bland-Altman analysis were calculated to evaluate the predictive performance in the testing group. The deep learning model based on SE-ResNet50 could predict surgical Hb loss with the best performance (R2 = 0.99, MAE = 11.09 mg, MAPE = 8.6%) compared with other predictive models, and Bland-Altman analysis also showed a bias of 1.343 mg with narrow limits of agreement (- 29.81 to 32.5 mg) between predictive and actual Hb loss. The interactive interface was also designed to display the real-time prediction of surgical Hb loss more intuitively. Thus, it is feasible for real-time estimation of surgical Hb loss using deep learning-based medical sponges image analysis, which was helpful for clinical decisions and technical evaluation.

Direct growth of single-chiral-angle tungsten disulfide nanotubes using gold nanoparticle catalysts.

Transition metal dichalcogenide (TMD) nanotubes offer a unique platform to explore the properties of TMD materials at the one-dimensional limit. Despite considerable efforts thus far, the direct growth of TMD nanotubes with controllable chirality remains challenging. Here we demonstrate the direct and facile growth of high-quality WS2 and WSe2 nanotubes on Si substrates using catalytic chemical vapour deposition with Au nanoparticles. The Au nanoparticles provide unique accommodation sites for the nucleation of WS2 or WSe2 shells on their surfaces and seed the subsequent growth of nanotubes. We find that the growth mode of nanotubes is sensitive to the temperature. With careful temperature control, we realize ~79% WS2 nanotubes with single chiral angles, with a preference of 30° (~37%) and 0° (~12%). Moreover, we demonstrate how the geometric, electronic and optical properties of the synthesized WS2 nanotubes can be modulated by the chirality. We anticipate that this approach using Au nanoparticles as catalysts will facilitate the growth of TMD nanotubes with controllable chirality and promote the study of their interesting properties and applications.

Partial versus radical nephrectomy for the treatment of pT3aN0M0 renal cell carcinoma: A propensity score analysis.

BACKGROUND: The survival benefit of partial nephrectomy (PN) in pT3a RCC patients is controversial. Here we aimed to explore the potential benefit of PN for pT3aN0M0 renal cell carcinoma (RCC). MATERIAL AND METHODS: Data of patients with pT3aN0M0 RCC who were diagnosed between 2010 and 2012 in the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database were retrospectively collected. Overall survival (OS) and cancer specific survival (CSS) were compared using a Cox proportional hazards model between PN and radical nephrectomy (RN) in pT3aN0M0 RCC. Propensity score (-adjusted, -stratified, -weighted, and -matched) analyses were performed to control for imbalances in individual risk factors. RESULTS: A total of 1277 patients with pT3aN0M0 RCC were identified, of whom 200 patients were treated with PN and 1077 patients were RN. PN showed favorable OS and CSS in 0-4 cm pT3aN0M0 RCC (P < 0.05), and similar OS and CSS in 4-7 cm pT3aN0M0 RCC, compared with RN using un-adjusted analyses. The Propensity score analyses further demonstrated the survival benefit of PN compared with the RN in 0-4 cm pT3aN0M0 RCC (P < 0.05). CONCLUSIONS: In this retrospective study, PN was associated with improved survival compared with RN in 0-4 cm pT3aN0M0 RCC. Moreover, survival was comparable between PN and RN in 4-7 cm pT3aN0M0 RCC. These data provided evidence that PN could be an alternative choice for T3aN0M0 RCC less than 7 cm. Particularly, patients with 0-4 cm pT3aN0M0 RCC might benefit from PN.

Guanylate binding protein 5 accelerates gastric cancer progression via the JAK1-STAT1/GBP5/CXCL8 positive feedback loop.

Guanylate binding protein 5 (GBP5) is a member of the interferon (IFN)-inducible large guanosine triphosphate hydrolases (GTPase) family that regulates cell-autonomous immunity and malignant tumor transformation. However, its specific roles and underlying mechanisms GBP5 in gastric cancer (GC) remain unknown. In this study, we aimed to determine the role GBP5 and underlying mechanism of GBP5 in GC cell progression. Potential oncogenic roles of GBP5 in GC as well as its relationship with the tumor immune microenvironment (TIME) were comprehensively evaluated using bioinformatics analysis. Protein expression levels of GBP5 and their correlation with clinicopathological features of patients were assessed using immunohistochemistry. In addition, diverse in vitro functional experiments were performed to identify the functions of GBP5 in GC. Downstream targets of GBP5 were identified using RNA-sequencing analysis and verified using western blotting or quantitative polymerase chain reaction analysis in different cell lines. GBP5 expression is commonly upregulated and promotes the proliferation and migration of GC cells. Mechanistically, GBP5 was regulated by the IFNγ-Janus kinase (JAK1)-signal transducer and activator of transcription 1 (STAT1) axis and induced CXCL8 expression. Interestingly, GBP5-induced CXCL8 regulated the JAK1-STAT1 signaling pathway to form a positive feedback loop. Moreover, GBP5 is closely related to the TIME and may be used as a biomarker for predicting the efficacy of immunotherapy. Our findings revealed a new JAK1-STAT1/GBP5/CXCL8 pathway and highlighted the value of GBP5 as a predictive biomarker and novel target for GC intervention.

The concept of developmental anatomy: the greater omentum should be resected in right-sided colon cancer?

BACKGROUND: The greater omentum is derived from the foregut, and the right hemicolon is derived from the midgut based on developmental anatomy. This study aimed to investigate whether the greater omentum should be resected in laparoscopic complete mesocolic excision based on developmental anatomy for right-sided colon cancer. METHODS: A total of 183 consecutive patients with right-sided colon cancer were recruited in this study between February 2020 and July 2022. Ninety-eight patients underwent standard laparoscopic complete mesocolic excision surgery (CME group). The presence of isolated tumor cells and micrometastases was detected in resected greater omentum by the HE staining and immunohistochemistry analysis. Based on developmental anatomy, laparoscopic CME surgery with greater omentum preservation (DACME group) was proposed and performed on 85 right-sided colon cancer patients. To overcome selection bias, we performed a 1:1 match between two groups using four variables: age, sex, BMI, and ASA scores. RESULTS: No isolated tumor cells and micrometastases were found in the resected greater omentum specimen in the CME group. After the propensity score, 81 pairs were balanced and analyzed. Patients in the DACME group showed shorter operative time (194.9 ± 16.4 min vs.201.5 ± 11.5 min, p = 0.002), less blood loss (23.5 ± 24.7 ml vs.33.6 ± 26.3 ml, p = 0.013), and the shorter hospital stays (9.6 ± 1.7 days vs.10.3 ± 2.0 days, p = 0.010) compared with patients in the CME group. In addition, patients in the DACME group had a lower incidence of postoperative complications (4.9% vs.14.8%, p = 0.035) than patients in the CME group. CONCLUSION: The greater omentum should be preserved during right-sided colon cancer surgery, laparoscopic CME surgery based on developmental anatomy is technically safe and feasible for right-sided colon cancer.

LncRNA GAS5 suppresses TGF-ß1-induced transformation of pulmonary pericytes into myofibroblasts by recruiting KDM5B and promoting H3K4me2/3 demethylation of the PDGFRα/ß promoter.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a condition that may cause persistent pulmonary damage. The transformation of pericytes into myofibroblasts has been recognized as a key player during IPF progression. This study aimed to investigate the functions of lncRNA growth arrest-specific transcript 5 (GAS5) in myofibroblast transformation during IPF progression. METHODS: We created a mouse model of pulmonary fibrosis (PF) via intratracheal administration of bleomycin. Pericytes were challenged with exogenous transforming growth factor-ß1 (TGF-ß1). To determine the expression of target molecules, we employed quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemical and immunofluorescence staining. The pathological changes in the lungs were evaluated via H&E and Masson staining. Furthermore, the subcellular distribution of GAS5 was examined using FISH. Dual-luciferase reporter assay, ChIP, RNA pull-down, and RIP experiments were conducted to determine the molecular interaction. RESULTS: GAS5 expression decreased whereas PDGFRα/ß expression increased in the lungs of IPF patients and mice with bleomycin-induced PF. The in vitro overexpression of GAS5 or silencing of PDGFRα/ß inhibited the TGF-ß1-induced differentiation of pericytes to myofibroblasts, as evidenced by the upregulation of pericyte markers NG2 and desmin as well as downregulation of myofibroblast markers α-SMA and collagen I. Further mechanistic analysis revealed that GAS5 recruited KDM5B to promote H3K4me2/3 demethylation, thereby suppressing PDGFRα/ß expression. In addition, KDM5B overexpression inhibited pericyte-myofibroblast transformation and counteracted the promotional effect of GAS5 knockdown on pericyte-myofibroblast transformation. Lung fibrosis in mice was attenuated by GAS5 overexpression but promoted by GAS5 deficiency. CONCLUSION: GAS5 represses pericyte-myofibroblast transformation by inhibiting PDGFRα/ß expression via KDM5B-mediated H3K4me2/3 demethylation in IPF, identifying GAS5 as an intervention target for IPF.

Chinese Medicine Plaster as A New Treatment for Surgical Site Infection in Patients with Cesarean Delivery: A Randomized, Double-Blind, Controlled Trial.

OBJECTIVE: To evaluate the efficacy of Chinese plaster containing rhubarb and mirabilite on surgical site infection (SSI) in patients with cesarean delivery (CD) by performing a randomized controlled trial. METHODS: This randomized controlled trial included 560 patients with CD due to fetal head descent enrolled at a tertiary teaching center between December 31, 2018 and October 31, 2021. Eligible patients were randomly assigned to a Chinese medicine (CM) group (280 cases) or a placebo group (280 cases) by a random number table, and were treated with CM plaster (made by rhubarb and mirabilite) or a placebo plaster, respectively. Both courses of treatment lasted from the day 1 of CD, followed day 2 until discharge. The primary outcome was the total number of patients with superficial, deep and organ/space SSI. The secondary outcome was duration of postoperative hospital stay, antibiotic intake, and unplanned readmission or reoperation due to SSI. All reported efficacy and safety outcomes were confirmed by a central adjudication committee that was unaware of the study-group assignments. RESULTS: During the recovery process after CD, the rates of localized swelling, redness and heat were significantly lower in the CM group than in the placebo group [7.55% (20/265) vs. 17.21% (47/274), P<0.01]. The durution of postoperative antibiotic intake was shorter in the CM group than in the placebo group (P<0.01). The duration of postoperative hospital stay was significantly shorter in the CM group than in the placebo group (5.49 ± 2.68 days vs. 8.96 ± 2.35 days, P<0.01). The rate of postoperative C-reactive protein elevation (≽100 mg/L) was lower in the CM group than in the placebo group [27.6% (73/265) vs. 43.8% (120/274), P<0.01]. However, there was no difference in purulent drainage rate from incision and superficial opening of incision between the two groups. No intestinal reactions and skin allergies were found in the CM group. CONCLUSIONS: CM plaster containing rhubarb and mirabilite had an effect on SSI. It is safe for mothers and imposes lower economic and mental burdens on patients undergoing CD. (Registration No. ChiCTR2100054626).

Insights into the streamwater age in the headwater catchments covered by glaciers and permafrost, Central Tibetan Plateau.

Improving our understanding of streamwater age knowledge is critical for revealing the complex hydrological processes in alpine cryosphere catchments. However, few studies on water age have been conducted in alpine cryosphere catchments due to the complicated and inclement environment. In this study, the Buqu catchment, a typical alpine catchment covered by glaciers and permafrost on the central Tibetan Plateau (TP), was selected as the study area. Using the sine-wave approach and a gamma model based on the seasonal cycle of stable isotopes in water, the young water fraction (Fyw) and mean transit time (MTT) of the Buqu catchment outlet and 23 sub-catchments was estimated to comprehensively reveal the potential driving mechanism of water age variability. The streamwater MTT for the entire catchment was 107 days, and 15.1 % of the streamwater was younger than 41 days on average. The estimated water age showed significant spatial heterogeneity with shorter water ages in high-elevation and glacier catchments and longer water ages in low-elevation and non-glacier catchments. Precipitation was the primary driver for spatial variations in water age, while the thickness of the permafrost active layer may function as an intermediate hub to drive water age variability. Mechanically, the thickness of the permafrost active layer controls the water ages by modifying the flow direction and length of water flow path. Spatially, this control mechanism is indirectly driven by the elevation gradient. The TDS concentration in streamwater is significantly related to water age, thus revealing a close link between water quality and hydrology. Our findings suggest that cryosphere retreats likely alter water age, thereby slowing water circulation rates and affecting water quality security under global warming. This study provides insights into the evolution of water ages, thereby deepening our understanding of the hydrological processes and guiding the protection of water resources in alpine headwater catchments.

Formation of DHP-DNA Adducts from Rat Liver Microsomal Metabolism of 1,2-Unsaturated Pyrrolizidine Alkaloid-Containing Plant Extracts and Dietary Supplements.

1,2-Unsaturated pyrrolizidine alkaloids (PAs) are carcinogenic phytochemicals. We previously determined that carcinogenic PAs and PA N-oxides commonly form a set of four (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA adducts, namely, DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4. This set of DHP-DNA adducts has been implicated as a potential biomarker of PA-induced liver tumor initiation from metabolism of individual carcinogenic PAs. To date, it is not known whether this generality occurs from metabolism of PA-containing plant extracts. In this study, we investigate the rat liver microsomal metabolism of nine PA-containing plant extracts and two PA-containing dietary supplements in the presence of calf thymus DNA. The presence of carcinogenic PAs and PA N-oxides in plant extracts was first confirmed by LC-MS/MS analysis with selected reaction monitoring mode. Upon rat liver microsomal metabolism of these PA-containing plant extracts and dietary supplements, the formation of this set of DHP-DNA adducts was confirmed. Thus, these results indicate that metabolism of PA-containing plant extracts and dietary supplements can generate DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4 adducts, thereby potentially initiating liver tumor formation.

Hydrogen evolution boosted by moderate Co3ZnC with current densities beyond 1000 mA cm-2.

Co3ZnC can efficiently boost the activity of Co@N, O co-doped carbons for hydrogen evolution. The results show that moderate Co3ZnC plays key roles in achieving an appropriate weighted Co 3d band centre, enhancing charger transfer and thus optimizing the electrochemical active surface area. Thus, a low overpotential of ∼219 mV can drive a high current density of 1000 mA cm-2 under the favourable condition of moderate Co3ZnC.

Protective effect of laparoscopic functional total mesorectal excision on urinary and sexual functions in male patients with mid-low rectal cancer.

BACKGROUND: Urinary and sexual dysfunctions are among the most common complications in rectal cancer surgery. This study aimed to investigate the protective effect of laparoscopic functional total mesorectum excision (TME) on urinary and sexual functions in male patients. METHODS: A total of 248 male patients with mid-low rectal cancer were recruited in this study between February 2017 and July 2020. To overcome selection bias, we performed a 1:1 match using six variables, including age, BMI, ASA score, tumor distance, clinical T stage, and tumor size. The urinary function was assessed by the International Prostate Symptom Score (IPSS), sexual function was assessed by a 5-item version of the International Index of Erectile Function (IIEF-5) and ejaculation grading at postoperative 3 and 12 months. RESULTS: 79 patients received functional TME surgery (FTME group), and 169 patients received routine TME surgery (RTME group). After the propensity score, 79 pairs were balanced and analyzed. Patients in the FTME group showed a lower IPSS score and higher IIEF-5 score than patients in the RTME group at postoperative 3 and 12 months. The incidence of ejaculation dysfunction for patients in the FTME group was lower than patients in the RTME group at postoperative 3 and 12 months. CONCLUSION: Laparoscopic functional total mesorectal excision was beneficial to faster recovery of urinary and sexual function for patients with rectal cancer, and it could be used as a superior surgical technique for pelvic autonomic nerve preservation in mid-low rectal cancer.

Fabrication of baicalein-encapsulated zeolitic imidazole framework as a novel nanocomposited wound closure material to persuade pH-responsive healing efficacy in post-caesarean section wound care.

Baicalein is a plant-derived compound, it has widespread attention among biomedical researchers due to its biocompatibility and efficient biological activities. But it has non-solubility in physiological conditions and short bioavailability in the clinical process. The Discovery of a stimuli-based drug delivery system (DDS) is a perfect strategy to improve the bioactivity of baicalin in post-caesarean section wound care. We prepared a baicalein-encapsulated pH-responsive DDS with a zeolite imidazole framework-8 (ZIF-8) as a carrier. We investigated the material characteristics of DDS in terms of crystal structure, surface area morphology, particle size, FTIR, UV-vis, Powder XRD, and BET analysis techniques. The in vitro cytotoxicity, biocompatibility, and cell proliferation properties of BA@ZIF-8 were assessed against human fibroblast L929 cells. In vitro studies showed that BA@ZIF-8 nanocomposite significantly enhanced the biocompatibility against L929 cells after 72 h post-exposure. The pH-responsive drug release kinetics shows excellent baicalein release under acidic conditions and without unwanted drug release in physiological conditions. Wound scratch assay results revealed, that BA@ZIF-8 nanocomposite-treated cells exhibit the fastest cell proliferation and migration process in a very short period. In the antibacterial activity study, nanocomposite exposed dose depended on inhibition against wound infectious pathogens. The overall study signifies that BA@ZIF-8 nano-DDSs are effective and suitable DDS for stimuli-based post-caesarean section wound care.

Concentrations, sources, fluxes, and absorption properties of carbonaceous matter in a central Tibetan Plateau river basin.

Carbonaceous matter (CM) (such as water-insoluble organic carbon (WIOC), black carbon (BC), and water-soluble organic carbon (WSOC)) has a significant impact on the carbon cycle and radiative forcing (RF) of glacier. Precipitation samples and glacier's snow/ice samples (snowpit, surface snow, and granular ice) (Xiao dongkemadi Glacier) were collected at the Dongkemadi River Basin (DRB) in the central Tibetan Plateau (TP) between May and October 2016 to investigate the characteristics and roles of CM in the TP River Basin. WIOC, BC, and WSOC concentrations in precipitation were relatively higher than that in snowpit, but lower than that in surface snow/ice, with the wet deposition fluxes of 0.10 ± 0.002, 0.04 ± 0.001, and 0.12 ± 0.002 g C m-2 yr-1 at DRB, respectively. The positive matrix factorization model identified four major sources (biomass burning source, secondary precursors, secondary aerosol, and dust source) of CM in precipitation at DRB. Two source areas (South Asia and the interior of TP) contributing to the pollution at DRB were identified using a potential source contribution function model, a concentration-weighted trajectory method, and the back-trajectory model. Moreover, the light-absorption by WSOC in the ultraviolet region was 23.0%, 12.1%, and 3.4% relative to the estimated total light-absorption in precipitation, snowpit, and surface snow/ice, respectively. Optical indices analysis revealed that WSOC in snowpit samples presented higher molecular weight, while presented higher aromatic and higher molecule sizes in surface snow/ice and precipitation samples, respectively. RF by WSOC relative to that of BC was estimated to be 17.6 ± 17.6% for precipitation, 10.9 ± 5.8% for snowpit, and 10.7 ± 11.6% for surface snow/ice, respectively, during the melt season in the central TP River Basin. These results help us understand how CM affects glaciers, and they can be utilized to create policies and recommendations that efficiently reduce emissions.