Genetic susceptibility to prostate cancer in Taiwan: A genome-wide association study.

We conducted the first genome-wide association study (GWAS) of prostate cancer (PCa) in Taiwan with 1844 cases and 80,709 controls. Thirteen independent single-nucleotide polymorphisms (SNPs) reached genome-wide significance (p < 5 × 10-8 ). Among these, three were distinct from previously identified loci: rs76072851 in CORO2B gene (15q23), odds ratio (OR) = 1.54, 95% confidence interval (CI), 1.36-1.76, p = 5.30 × 10-11 ; rs7837051, near two long noncoding RNA (lncRNA) genes, PRNCR1 and PCAT2 (8q24.21), OR = 1.41 (95% CI, 1.31-1.51), p = 8.77 × 10-21 ; and rs56339048, near an lncRNA gene, CASC8 (8q24.21), OR = 1.25 (95% CI, 1.16-1.35), p = 2.14 × 10-8 . We refined the lead SNPs for two previously identified SNPs in Taiwanese: rs13255059 (near CASC8), p = 9.02 × 10-43 , and rs1456315 (inside PRNCR1), p = 4.33 × 10-42 . We confirmed 35 out of 49 GWAS-identified East Asian PCa susceptibility SNPs. In addition, we identified two SNPs more specific to Taiwanese than East Asians: rs34295433 in LAMC1 (1q25.3) and rs6853490 in PDLIM5 (4q22.3). A weighted genetic risk score (GRS) was developed using the 40 validated SNPs and the area under the receiver-operating characteristic curve for the GRS to predict PCa was 0.67 (95% CI, 0.63-0.71). These identified SNPs provide valuable insights into the molecular mechanisms of prostate carcinogenesis in Taiwan and underscore the significant role of genetic susceptibility in regional differences in PCa incidence.

The genome-wide association study of serum IgE levels demonstrated a shared genetic background in allergic diseases.

Immunoglobulin E (IgE) synthessis is highly related to a variety of atopic diseases, and several genome-wide association studies (GWASs) have demonstrated the association between genes and IgE level. In this study, we conducted the largest genome-wide association study of IgE involving a Taiwanese Han population. Eight independent variants exhibited genome-wide significance. Among them, an intronic SNP of CD28, rs1181388, and an intergenic SNP, rs1002957030, on 11q23.2 were identified as novel signals for IgE. Seven of the loci were replicated successfully in a meta-analysis using data on Japanese population. Among all the human leukocyte antigen (HLA) regions, HLA-DQA1*03:02 - HLA-DQB1*03:03 was the most significant haplotype (OR = 1.25, SE = 0.02, FDR = 1.6 × 10-14), corresponding to HLA-DQA1 Asp160 and HLA-DQB1 Leu87 amino acid residues. The genetic correlation showed significance between IgE and allergic diseases including asthma, atopic dermatitis, and pollinosis. IgE PRS was significantly correlated with total IgE levels. Furthermore, the top decile IgE polygenic risk score (PRS) group had the highest risk of asthma for the Taiwan Biobank and Biobank Japan cohorts. IgE PRS may be used to aid in predicting the occurrence of allergic reactions before symptoms occur and biomarkers are detectable. Our study provided a more comprehensive understanding of the impact of genomic variants, including complex HLA alleles, on serum IgE levels.

Regulatory T cells in inflamed liver are dysfunctional in murine primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a chronic autoimmune disease characterized by immune-mediated destruction of intrahepatic small bile ducts. CD8 T cells play a critical role in biliary destruction. However, regulatory T cells (Tregs) have also been identified in the portal tracts of PBC patients. This study tested the hypothesis that hepatic Tregs in PBC were dysfunctional in suppressing immune responses in disease by using our human PBC-like autoimmune cholangitis (AIC) mouse model induced by 2-octynoic acid-conjugated ovalbumin (2-OA-OVA). Our results showed that female and male mice immunized with 2-OA-OVA developed AIC; however, female AIC mice had more severe liver inflammation and fibrosis than male AIC mice. Levels of functional effector CD8 T cells and their chemoattractants, CXCL9 and CXCL10, in the liver were markedly elevated in female AIC mice than in male AIC mice. These results reinforce that CD8 T cells are the primary effector cells in PBC. The number of hepatic Tregs in AIC mice was also higher than in saline-treated mice, but there was no difference between male and female AIC mice. The suppressive function of AIC Tregs was evident despite a discrepancy in the changes in their co-inhibitory receptors and inhibitory cytokines. However, the expansion of hepatic Tregs by low-dose IL-2 treatment did not reduce immune responses to AIC, which may be due to the dysfunction of Tregs in inhibiting T cells. In conclusion, the function of Tregs in the inflamed liver of PBC was insufficient, and low-dose IL-2 treatment could not restore their function to suppress pathological immune responses. Transferring normal Tregs or directly targeting effector CD8 T cells may be beneficial for treating PBC.

IL-21, not IL-17A, exacerbates murine primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease caused by intrahepatic bile duct injuries, resulting in fibrosis, cirrhosis, and eventually liver failure. T helper (Th) 17 cells are proposed to involve in the pathogenesis of PBC. However, how and which Th17 cell-derived cytokines affect PBC remains unclear. In this study, we investigated the effects of Th17 effector cytokines, including interleukin (IL)-17A, IL-17F, and IL-21 in PBC using a xenobiotic-induced mouse model of autoimmune cholangitis (inducible chemical xenobiotic models of PBC) treated with cytokine-expressing adeno-associated virus. Our results showed that administration of IL-17A, the well-known main cytokine produced by Th17 cells, did not augment liver inflammation or fibrosis. In contrast, we noted IL-17A-treated mice had lower hepatic Th1 cell numbers and higher hepatic CD11b+Ly6G+ polymorphonuclear myeloid-derived suppressor cell numbers. IL-17F did not alter liver inflammation or fibrosis. However, the administration of IL-21 exacerbated liver inflammatory responses and portal cell infiltration. IL-21 markedly increased the numbers of activated CD8+ T cells and liver tissue-resident memory CD8+ T cells. Moreover, IL-21 aggravates liver fibrosis in mice with autoimmune cholangitis. These results emphasized that not IL-17A but IL-21 in Th17 cell-derived cytokines affected the pathogenesis of PBC. IL-21 enhanced liver inflammation and progression to fibrosis by enhancing the numbers and effector activities of CD8+ T cells. Delineation of the effects of different Th17 effector cytokines in PBC offers clues for developing new therapeutic approaches.

The impact of intensity-modulated radiotherapy in conjunction with chemotherapy on proximal pT3N0 rectal cancer patients after total mesorectum excision.

BACKGROUND: This study aimed to ascertain if the incorporation of intensity-modulated radiotherapy (IMRT) with chemotherapy (CTx) offered any advantages for patients diagnosed with stage pT3N0 rectal cancer located in the proximal (upper) region following a complete total mesorectum excision (TME). METHODS: We retrospectively examined medical records of stage II/III rectal cancer patients who had undergone CTx or concurrent chemoradiation (CCRT) with IMRT after a successful TME. We juxtaposed a variety of survival outcomes across two patient cohorts. Each outcome was further classified according to Gunderson's risk stratification between proximal and distal (middle and low) rectal cancer patients, and we evaluated the factors associated with each outcome. RESULTS: The median follow-up duration was 4.9 years. Our research comprised 236 rectal adenocarcinoma patients treated at our institution between 2007 and 2019. They received either the CTx (n = 135) or the CCRT (n = 101) with 10-year locoregional recurrence-free survival (LRRFS) of 90.1% and 96.1%, respectively (p = 0.163). However, after performing multivariate adjustments, a pattern emerged hinting at a better LRRFS for the CCRT group (p = 0.052). Perforation had a strong correlation with locoregional recurrence. No significant differences were observed in other survival between the two treatment arms and their respective subgroups. The CCRT group witnessed significantly higher immediate and chronic complications with p = 0.007 and 0.009, respectively. The CCRT group had two secondary cancer-related fatalities (2%, one attributed to IMRT), and another reported by the CTx group (1%). The sole classified locoregional recurrence within the cohort of 37 individuals treated with CTx for proximal pT3N0 rectal cancer was, in fact, the development of sigmoid colon cancer. CONCLUSION: The results suggest that for patients with proximal pT3N0 rectal cancer post-TME, IMRT is better when not combined with CTx, except in highly perilous scenarios or those involving perforation.

A meta-analysis of treatment for early-stage cervical cancer: open versus minimally invasive radical trachelectomy.

BACKGROUND: In previous systematic reviews, meta-analysis was lacking, resulting in the statistical difference between the data of different surgeries being impossible to judge. This meta-analysis aims to contrast the fertility results and cancer outcomes between open and minimally invasive surgery. METHOD: We systematically searched databases including PubMed, Embase, Cochrane, and Scopus to collect studies that included open and minimally invasive radical trachelectomy. A random-effect model calculated the weighted average difference of each primary outcome via Review Manager V.5.4. RESULT: Eight studies (1369 patients) were incorporated into our study. For fertility results, the Open group excels MIS group in pregnancies-Third trimester delivery [OR = 2.68; 95% CI (1.29, 5.59); P = 0.008]. Nevertheless, there is no statistical difference in clinical pregnancy, miscarriage, and second-trimester rate. Concerning cancer outcomes, no difference was detected in the overall survival [OR = 1.56; 95% CI (0.70, 3.45); P = 0.27] and recurrence [OR = 0.63; 95% CI (0.35, 1.12); P = 0.12]. Concerning surgery-related outcomes, the comprehensive effects revealed that the estimated blood loss of the Open group was higher than that of the MIS group[MD = 139.40; 95% CI (79.05, 199.75); P < 0.0001]. However, there was no difference between the postoperative complication rate in the two groups [OR = 1.52; 95% CI (0.89, 2.60); P = 0.12]. CONCLUSION: This meta-analysis suggested that the fertility result of the Open group may be better than the MIS group, while the MIS group has better surgery-related outcomes. Owing to the poor cases of our study, a more robust conclusion requires more relevant articles in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022352999.

Enhanced skin neocollagenesis through the transdermal delivery of poly-L-lactic acid microparticles by using a needle-free supersonic atomizer.

In this study, a spindle-type nozzle was designed to accelerate poly-L-lactic acid (PLLA) microparticles to supersonic velocities for the transdermal delivery of these microparticles to rats. This approach is needle- and pain-free and enhances skin collagen regeneration. The addition of PLLA microparticles at a concentration of 2 mg/mL did not hinder the growth of 3 T3 fibroblasts and Raw264.7 macrophages. The TNF-α assay revealed no obvious inflammation effect of PLLA microparticles at a concentration of 1 mg/mL. A time-lapse recording revealed that after being cocultured with PLLA microparticles for 24 h, Raw264.7 macrophages gradually approached and surrounded the PLLA microparticles. When 3 T3 fibroblasts were cocultured with Raw264.7 macrophages, which were stimulated using PLLA microparticles, collagen synthesis was increased by approximately 60 % compared with that in samples without PLLA microparticles. In vivo animal experiments indicated that after the transdermal delivery of 10 shots of PLLA microparticles through the supersonic atomizer, no obvious changes or damage to the back skin of Sprague-Dawley rats was observed. More importantly, numerous PLLA microparticles penetrated the rat epidermis into the dermal layer. We found macrophages and fibroblasts present close to the PLLA microparticles. Moreover, only mild or no inflammation reaction was observed. Masson staining revealed that after 6-week implantation, 6 % and 12 % of PLLA microparticles significantly stimulated collagen regeneration in 6-week-old and 32-week-old rats. In addition, picrosirius red staining revealed a significant increase in collagen regeneration, especially for type III collagen, following the 6-week implantation of PLLA microparticles. In summary, this study demonstrated an easy, pain-free, nondestructive approach for introducing PLLA microparticles into the dermal layer by using a supersonic atomizer to stimulate collagen regeneration in vivo.

Antifouling and Chemical-Resistant Nanofiltration Membrane Modulated by a Functionalized MWCNT Interlayer for Efficient Dye/Salt Separation at High Salinity.

Dye/salt separation in textile wastewater is of great importance. Membrane filtration technology is an environmentally friendly and effective approach to solve this issue. In this study, a thin-film composite membrane with a tannic acid (TA)-modified carboxylic multiwalled carbon nanotube (MWCNT) interlayer (M-TA) was prepared by interfacial polymerization with amino-functionalized graphene quantum dots (NGQDs) acting as aqueous monomers. The addition of the M-TA interlayer favored the formation of a thinner, more hydrophilic, and smoother selective skin layer for the composite membrane. The pure water permeability of the M-TA-NGQDs membrane was ∼9.32 L m-2 h-1 bar-1, which was higher than that of the NGQDs membrane without the interlayer. Meanwhile, the M-TA-NGQDs membrane presented better methyl orange (MO) rejection (97.79%) than the NGQDs membrane (87.51%). The optimal M-TA-NGQDs membrane exhibited excellent dye rejection (Congo red (CR): 99.61%; brilliant green (BG): 96.04%) and low salt rejection (NaCl < 15%). Noticeably, the M-TA-NGQDs membrane displayed effective selective separation performance (CR and BG > 99%) for dye/NaCl mixed solutions even at a high NaCl concentration of 50,000 mg/L. Furthermore, the M-TA-NGQDs membrane presented high water permeability recovery ratio values (91.02-98.20%). Importantly, the M-TA-NGQDs membrane showed excellent chemical stability (acid/alkali resistance). Generally, the fabricated M-TA-NGQDs membrane exhibited a great prospect for applications in dye wastewater treatment and water recycling, especially for the effective selective separation of dye/salt mixtures for high-salinity textile dyeing wastewater.

A meta-analysis: single or double dartos flap layer in tubularized incised plate urethroplasty to prevent urethrocutaneous fistula?

Backgrounds: Urethrocutaneous fistula is one of the most common complications after urethroplasty. This meta-analysis aims to evaluate the superiority of double dartos flap to single dartos flap in preventing fistula during tubularized incised plate urethroplasty (TIPU), which is one of the most frequently used operations for hypospadias. Methods: We extracted clinical trials under the following included criteria: (1) children with TIPU; (2) a comparison of single and double flap layer; and (3) record of complications with the following excluded criteria: (1) non-comparison and (2) lack of data. Finally, 13 studies from PubMed, Cochrane Library, Scopus, and Embase have been investigated, with a total of 1,185 patients from 2005 to 2022. The quality assessment was conducted according to the Cochrane handbook and the Newcastle-Ottawa scale. A mixed-effect model was utilized to weigh the risk of fistula, phallic rotation, meatal stenosis, and wound dehiscence by the Review Manager V.5.4 software. Results: The double dartos flap layer group excels in descending the risk of postoperative fistula [odds ratio (OR) = 9.56; 95% confidence interval (CI) (4.76, 19.22); P < 0.00001] and phallic rotation [OR = 31.26; 95% CI (9.60, 101.84); P < 0.00001], while there are no differences in the rate of meatal stenosis [OR = 1.49; 95% CI (0.73, 2.70); P = 0.31] and wound dehiscence [OR = 2.30; 95% CI (0.80, 6.63); P = 0.12]. Conclusions: The routine utility of a double dartos flap layer is recommended as a potential treatment during the tubularized incised plate urethroplasty. Systematic Review Registration: identifier PROSPERO CRD42022366294.

Hippocampal-sparing whole-brain radiotherapy under coplanar or noncoplanar VMAT.

Whole-brain radiotherapy (WBRT) can alleviate symptoms in patients with brain metastases. However, WBRT may damage the hippocampus. Volumetric modulated arc therapy (VMAT) can achieve a suitable coverage of the target region and a more conforming dose distribution whereas decreasing the dose to organs-at-risk (OARs). Herein, we aimed to compare the differences between treatment plans utilizing coplanar VMAT and noncoplanar VMAT in hippocampal-sparing WBRT (HS-WBRT). Ten patients were included in this study. For each patient, the Eclipse A10 treatment planning system was used to generate 1 coplanar VMAT (C-VMAT) and 2 noncoplanar VMAT treatment plans with various beam angles (noncoplanar VMAT A [NC-A] and noncoplanar VMAT B [NC-B]) for HS-WBRT. The prescribed dose was 30 Gy in 12 fractions. Treatment plans were established based on the OAR dose constraints of the Radiation Therapy Oncology Group 0933 (RTOG 0933). Parameters such as the global maximum dose, dose conformity, dose homogeneity of plans, and OAR doses were evaluated. The maximum biologically equivalent doses in 2-Gy fractions (EQD2) of OARs in C-VMAT were 9.17 ± 0.61, 42.79 ± 2.00, and 42.84 ± 3.52 Gy in the hippocampus, brain stem, and optic chiasm, respectively, which were the lowest among the 3 treatment plans. There was no significant difference in dose conformity among the 3 treatment plans. However, NC-A had a slightly better conformity than C-VMAT and NC-B. NC-A had the best homogeneity, and NC-B had the worst homogeneity (p = 0.042). NC-A and NC-B had the lowest and highest global dose maximum, respectively. Therefore, NC-A, which had an intermediate performance in terms of OAR doses, had the best quality parameters. We used the quality score table based on the p-value to evaluate the significant difference between each treatment technique from the multiparameter results. In terms of treatment plan parameters, only NC-A received a score of 2; for OAR doses, C-VMAT, NC-A, and NC-B received a score of 6, 3, and 5, respectively. For the overall evaluation, C-VMAT, NC-A, and NC-B received a total score of 6, 5, and 5, respectively. Rather than noncoplanar VMAT, 3 full-arc C-VMATs should be utilized in HS-WBRT. C-VMAT can simultaneously maintain treatment plan quality and decrease patient alignment time and total treatment time.

Measurements and Modelling of Thermally Induced Warpages of DIMM Socket Server PCB Assembly after Solder Reflow Processes.

The thermal warpage of a server-computer-used DIMM socket-PCB assembly after the solder reflow process is studied experimentally, theoretically, and numerically, especially along the socket lines and over the entire assembly. Strain gauge and shadow moiré are used for determining the coefficients of thermal expansion of the PCB and DIMM sockets and for measuring the thermal warpages of the socket-PCB assembly, respectively, while a newly proposed theory and a finite element method (FEM) simulation are used to calculate the thermal warpage of the socket-PCB assembly in order to understand its thermo-mechanical behavior and then further identify some important parameters. The results show that the theoretical solution validated by the FEM simulation provides the mechanics with the critical parameters. In addition, the cylindrical-like thermal deformation and warpage, measured by the moiré experiment, are also consistent with the theory and FEM simulation. Moreover, the results of the thermal warpage of the socket-PCB assembly from the strain gauge suggest a warpage dependence on the cooling rate during the solder reflow process, due to the nature of the creep behavior in the solder material. Finally, the thermal warpages of the socket-PCB assemblies after the solder reflow processes are provided through a validated FEM simulation for future designs and verification.

Low-pressure thin-film composite nanofiltration membranes with enhanced selectivity and antifouling property for effective dye/salt separation.

For better sustainable resource recovery and elevating the separation efficiency of dye/salt mixture, it is essential to develop an appropriate nanofiltration membrane for the treatment of textile dyeing wastewater containing relatively smaller molecule dyes. In this work, a novel composite polyamide-polyester nanofiltration membrane was fabricated by tailoring amino functionalized quantum dots (NGQDs) and ß-cyclodextrin (CD). An in-situ interfacial polymerization occurred between the synthesized NGQDs-CD and trimesoyl chloride (TMC) on the modified multi-carbon nanotubes (MWCNTs) substrate. The incorporation of NGQDs significantly elevated the rejection (increased by âˆ¼ 45.08%) of the resultant membrane for small molecular dye (Methyl orange, MO) compared to the pristine CD membrane at low pressure (1.5 bar). The newly developed NGQDs-CD-MWCNTs membrane exhibited enhanced water permeability without compromising the dye rejection compared to the pure NGQDs membrane. The improved performance of the membrane was primarily attributed to the synergistic effect of functionalized NGQDs and the special hollow-bowl structure of CD. The optimal NGQDs-CD-MWCNTs-5 membrane expressed pure water permeability of 12.35 L m-2h-1 bar-1 at the pressure of 1.5 bar. Noteworthily, the NGQDs-CD-MWCNTs-5 membrane not only showed high rejection for the larger molecular dye of Congo Red (CR, 99.50%) but also for the smaller molecular dye of MO (96.01%) and Brilliant Green (BG, 95.60%) with the permeability of 8.81, 11.40, and 6.37 L m-2h-1 bar-1, respectively at low pressure (1.5 bar). The rejection of inorganic salts by the NGQDs-CD-MWCNTs-5 membrane was 17.20% for sodium chloride (NaCl), 14.30% for magnesium chloride (MgCl2), 24.63% for magnesium sulfate (MgSO4), and 54.58% for sodium sulfate (Na2SO4), respectively. The great rejection of dyes remained in the dye/salt binary mixed system (higher than 99% for BG and CR, <21% for NaCl). Importantly, the NGQDs-CD-MWCNTs-5 membrane exhibited favorable antifouling performance and potential good operation stability performance. Consequently, the fabricated NGQDs-CD-MWCNTs-5 membrane suggested a prospective application for the reuse of salts and water in textile wastewater treatment owing to the effective selective separation performance.

Apoptotic biliary epithelial cells and gut dysbiosis in the induction of murine primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a female-predominant liver autoimmune disease characterized by the specific immune-mediated destruction of the intrahepatic small bile duct. Although apoptosis of biliary epithelial cells (BECs) and alterations in gut microbiota are observed in patients with PBC, it is still unclear whether these events happen in the early stage and cause the breakdown of tolerance in PBC. In this study, we examined the early events in the loss of tolerance in our well-defined 2-OA-OVA-induced murine autoimmune cholangitis (AIC) model. We report herein that apoptosis of BECs was notable in the early stage of murine AIC. An altered gut microbiota, in particular, an increased percentage of gram-positive Firmicutes in AIC mice was also observed. BECs in AIC mice expressed adhesion molecule ICAM-1, cytokines/chemokines TNF-α, CCL2, CXCL9, CXCL10, and toll-like receptor (TLR) 2. Moreover, BECs treated with TLR2 ligand had elevated apoptosis and CXCL10 production. These data collectively suggest a new mechanism of tolerance breakdown in AIC. Altered gut microbiota induces apoptosis of BECs through TLR2 signaling. BECs secrete chemokines to recruit CD8 T cells to damage BECs further.

Effects of the experience of breastfeeding-friendly practices and breastfeeding intention and self-efficacy on breastfeeding behavior: a cohort study in Taiwan.

BACKGROUND: Approximately 80% of births in Taiwan occurred in Baby-Friendly accredited facilities, although the trend of exclusively breastfeeding infants until 6 months of age has stagnated in the last ten years. To guide breastfeeding promotion interventions during postnatal stays and encourage mothers to continue breastfeeding for the first 6 months, factors associated with breastfeeding behaviors to 6 months post-delivery must be investigated. This study explored the relationships among breastfeeding intention, experience of breastfeeding-friendly practices, breastfeeding self-efficacy, and breastfeeding behavior at four and 6 months after childbirth. METHODS: In this longitudinal cohort study, women who gave birth to healthy newborns at two Baby-Friendly hospitals in Taiwan and who had initiated breastfeeding were recruited two to 4 days after giving birth. Data were collected three to 5 days after childbirth during hospitalization and at one, two, four, and 6 months after childbirth using a self-developed questionnaire to measure breastfeeding intention and the experience of breastfeeding-friendly practices, and the traditional Chinese version of the Breastfeeding Self-Efficacy Scale-Short Form to measure self-efficacy. RESULTS: A total of 155 women completed the questionnaires five times within 6 months. The determinants of exclusive breastfeeding at 4 months and any breastfeeding at 6 months were the intention to breastfeed for over 6 months; a higher score for the experience of breastfeeding-friendly practices; and a higher level of breastfeeding self-efficacy during that period. The experience of breastfeeding-friendly practices during hospitalization did not predict breastfeeding behavior at 4 and 6 months. Intending to breastfeed for less than 4 months and lower breastfeeding self-efficacy during the hospital stay were both associated with shorter breastfeeding durations of less than 6 months after childbirth. CONCLUSIONS: Longer intended duration of breastfeeding, sustaining breastfeeding-friendly practices after discharge, and maintenance of a higher level of breastfeeding self-efficacy were the determinants of breastfeeding at 4 and 6 months. Healthcare professionals in Taiwan must support breastfeeding-friendly practices and consider interactive interventions to promote continued breastfeeding at different stages during the first 6 months after childbirth on the basis of the mother's breastfeeding plan and breastfeeding self-efficacy during their postnatal hospitalization.

Loosely Sandwich-Structured Membranes Decorated with UiO-66-NH2 for Efficient Antibiotic Separation and Organic Solvent Resistance.

Thin-film nanocomposite (TFN) membranes with efficient molecular separation and organic solvent resistance are active in demand in wastewater treatment and resource reclamation, meeting the goal of emission peaks and carbon neutrality. In this work, a simple and rational design strategy has been employed to construct a sandwich-structured membrane for removing fluoroquinolone antibiotics and recycling organic solvents. The sandwich-structured membrane is composed of a porous substrate, a hydrophilic tannic acid-polyethyleneimine (TA-PEI) interlayer, and a polyamide (PA) selective layer decorated with metal-organic framework (PA-MOF). Results manifest that the hydrophilic TA-PEI interlayer played a bridging and gutter effect to achieve effective control in amide storage, amine diffusion, and nanomaterial downward leakage at the immiscible interface. The PA-MOF selective layer has been changed to a loosely crumpled surface, endowing functionalities on the sandwich-structured membrane that included limited pores, strengthened electronegativity, and stronger hydrophilicity. Thus, an enhanced water flux of 87.23 ± 7.43 LMH was achieved by the TFN-2 membrane (0.04 mg·mL-1 UiO-66-NH2), which is more than five times that of the thin-film composite membrane (17.46 ± 3.88 LMH). The rejection against norfloxacin, ciprofloxacin, and levofloxacin is 92.94 ± 1.60%, 94.62 ± 1.29%, and 96.92 ± 1.05%, respectively, effectively breaking through the "trade-off" effect between membrane permeability and rejection efficiency. Further antifouling results showed that the sandwich-structured membrane had lower flux decay ratios (3.36∼7.07%) and higher flux recovery ratios (93.40∼98.40%), as well as superior long-term stability after 30 days of filtration. Moreover, organic solvent resistance testing confirms that the sandwich-structured membrane maintained stable solvent flux and better recovery rates in ethanol, acetone, isopropanol, and N,N-dimethylformamide. Detailed nanofiltration mechanism studies revealed that these outstanding performances are based on the joint effect of the TA-PEI interlayer and PA-MOF selective layer, proposing a new perspective to break through the bottleneck of nanofiltration application in a complex environment.

[Electroacupuncture preconditioning improves pulmonary function via inhibiting inflammatory response and up-regulating expression of ACE2 and Ang (1-7) in lipopolysaccharide-induced acute lung injury rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36) pretreatment on lung functions, inflammatory response, and levels of angiotensin-converting enzyme 2 (ACE2) and angiotensin (1-7) ï¼»Ang (1-7)ï¼½ in rats with sepsis-induced acute lung injury (ALI), so as to explore its mechanisms underlying improvement of ALI. METHODS: Thirty male SD rats were randomly divided into normal, model and EA groups (n=10 in each group). The sepsis-related ALI model was established by intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg). Rats of the EA group received EA (4 Hz/20 Hz, 1-3 mA) stimulation at bilateral ST36 for 30 min, once each day, for 7 days before modeling. The lung functions including forced vital capacity (FVC), forced expiratory volume at 0.1 second (FEV0.1) and FEV0.3 were detected using a respiratory function detector for small animals at 3 h after modeling. The bronchoalveolar lavage fluid (BALF) was collected for assaying the contents of Ang (1-7), tumor necrosis factor-α (TNF-α) and interleukin-1 ß (IL-1ß) using ELISA. The lung wet/dry weight (W/D) ratio, FEV0.1/FVC, and FEV0.3/FVC were calculated. The histopathological changes of lung tissues were displayed by hematoxylin-eosin (H.E.) staining. The expression of ACE2 and mitochondrial assembly receptor (MasR) mRNAs and proteins in the lung tissue was detected by fluorescence quantitative real-time PCR and Western blot, separately. RESULTS: Following modeling, the levels of FVC, FEV0.1, FEV0.3, ratio of FEV0.1/FVC and FEV0.3/FVC, content of Ang (1-7) in the BALF, and the expression levels of ACE2 and MasR mRNAs and proteins in the lung tissue were significantly decreased (P<0.01), while the level of W/D ratio and TNF-α and IL-1ß contents in the BALF significantly increased (P<0.01) in the model group relevant to the normal group. In comparison with the model group, the levels of FVC, FEV0.1, FEV0.3, ratio of FEV0.1/FVC and FEV0.3/FVC, content of Ang (1-7) in the BALF, and expression levels of ACE2 and MasR mRNAs and proteins in the lung tissue were significantly increased (P<0.05, P<0.01), whereas the level of W/D ratio, and TNF-α and IL-1ß contents in the BALF were significantly decreased (P<0.05, P<0.01) in the EA group. H.E. staining showed pulmonary interstitial edema and alveolar septum thickening with severe inflammatory cell infiltration in the model group, which was relatively milder in the EA group. CONCLUSION: EA preconditioning at ST36 can improve pulmonary function in sepsis-related ALI rats, which may be related to its effects in inhibiting inflammatory response and up-regulating ACE2 and MasR expression and Ang (1-7) content in the lung tissue.

Meta-analysis of the association between new hypoglycemic agents and digestive diseases.

BACKGROUND: New hypoglycemic agents include sodium-glucose cotransporter-2 inhibitors (SGLT2is), glucagon-like peptide 1 receptor agonists (GLP1RAs), and dipeptidyl peptidase-4 inhibitors (DPP4is). The association between each class of these new hypoglycemic drugs and the risks of various digestive system diseases is unknown. We aimed to explore this relationship by performing a meta-analysis. METHODS: We included large randomized trials of SGLT2is, GLP1RAs, and DPP4is. Outcomes of interest were 91 kinds of digestive diseases including 75 kinds of gastrointestinal disorders and 16 kinds of hepatobiliary disorders. Meta-analysis was done to generate pooled risk ratio (RR) and 95% confidence interval (CI). Subgroup analysis was conducted according to 3 different drug classes. RESULTS: We included 21 large trials in this meta-analysis. Compared with placebo, GLP1RAs were associated with the higher risks of gastric ulcer hemorrhage (RR 2.68, 95% CI 1.07-6.68; Pdrug = .035; I2 = 0), pancreatitis (RR 1.48, 95% CI 1.02-2.15; Pdrug = .041; I2 = 0), cholangitis acute (RR 5.96, 95% CI 1.04-34.08; Pdrug = .045; I2 = 0), and cholecystitis acute (RR 1.52, 95% CI 1.08-2.15; Pdrug = .017; I2 = 1.5%), but were not significantly associated with the occurrences of the other 87 kinds of digestive diseases (Pdrug ranged from .064 to .999). SGLT2is versus placebo were not significantly associated with the occurrences of 91 kinds of digestive diseases (Pdrug ranged from .077 to .995). DPP4is versus placebo were not significantly associated with the occurrences of 91 kinds of digestive diseases (Pdrug ranged from .085 to .999). CONCLUSIONS: Neither SGLT2is nor DPP4is are associated with the occurrences of various kinds of digestive diseases, whereas GLP1RAs are associated with the higher risks of 4 kinds of digestive diseases, namely, gastric ulcer hemorrhage, pancreatitis, cholangitis acute, and cholecystitis acute. These findings seem to suggest that GLP1RAs are not applicable for patients at high risk of 4 specific digestive diseases, whereas SGLT2is and DPP4is are safe for patients susceptible to digestive diseases. However, our findings require to be further verified by future studies with sufficient statistical power.

Reparative Efficacy of Liposome-Encapsulated Oleanolic Acid against Liver Inflammation Induced by Fine Ambient Particulate Matter and Alcohol in Mice.

Airborne fine particulate matter (PM2.5) is a severe problem and is associated with health issues including liver diseases. Workers performing manual labor tend to be alcohol consumers during work, where they are also exposed to PM2.5. Long-term PM2.5 exposure can increase oxidative stress, leading to inflammation. Whether long-term exposure to air pollution and alcohol synergistically increases liver fibrosis risk warrants investigation. Oleanolic acid (OA)-a triterpenoid-has antioxidant and anti-inflammatory activities, but its low water solubility and cytotoxicity impair its potential applications. In this study, we fabricated liposomal OA nanoparticles (Lipo-OAs); then, we evaluated the anti-inflammatory effect on exposed cells and the ameliorative effect of Lipo-OAs on PM2.5 and alcohol-induced liver fibrosis in mice. The half maximal inhibitory concentration of PM2.5 for hepatic stellate cells was 900 µg/mL; at a concentration of ≥600 µg/mL, PM2.5 significantly increased interleukin-6 and tumor necrosis factor-α production. OA encapsulation in Lipo-OAs, 353 ± 140 nm in diameter with 79% encapsulation efficiency, significantly reduced OA cytotoxicity. Lipo-OAs treatment significantly reduced alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase levels; histologically, it alleviated steatosis and improved Ishak's modified HAI score. In conclusion, Lipo-OAs have potential anti-inflammatory and reparative effects for PM2.5 and alcohol-induced liver injury treatment.