Hydrogen-Bonded Thiol Undergoes Unconventional Excited-State Intramolecular Proton-Transfer Reactions.

The chapter on the thiol-related hydrogen bond (H-bond) and its excited-state intramolecular proton-transfer (ESIPT) reaction was recently opened where compound 4'-diethylamino-3-mercaptoflavone (3NTF) undergoes ESIPT in both cyclohexane solution and solid, giving a 710 nm tautomer emission with an anomalously large Stokes shift of 12,230 cm-1. Considering the thiol H-bond to be unconventional compared to the conventional Pauling-type -OH or -NH H-bond, it is thus essential and timely to probe its fundamental difference between their ESIPT. However, thiol-associated ESIPT tends to be nonemissive due to the dominant nπ* character of the tautomeric lowest excited state. Herein, based on the 3-mercaptoflavone scaffold and π-elongation concept, a new series of 4'-substituted-7-diethylamino-3-mercaptoflavones, NTFs, was designed and synthesized with varied H-bond strength and 690-720 nm tautomeric emission upon ultraviolet (UV) excitation in cyclohexane. The order of their H-bonding strength was experimentally determined to be N-NTF < O-NTF < H-NTF < F-NTF, while the rate of -SH ESIPT measured by fluorescence upconversion was F-NTF (398 fs)-1 < H-NTF (232 fs)-1 < O-NTF (123 fs)-1 < N-NTF (101 fs)-1 in toluene. Unexpectedly, the strongest H-bonded F-NTF gives the slowest ESIPT, which does not conform to the traditional ESIPT model. The results are rationalized by the trend of carbonyl oxygen basicity rather than -SH acidity. Namely, the thiol acidity relevant to the H-bond strength plays a minor role in the driving force of ESIPT. Instead, the proton-accepting strength governs ESIPT. That is to say, the noncanonical thiol H-bonding system undergoes an unconventional type of ESIPT.

Antagonizing apolipoprotein J chaperone promotes proteasomal degradation of mTOR and relieves hepatic lipid deposition.

BACKGROUND AND AIMS: Overnutrition-induced activation of mammalian target of rapamycin (mTOR) dysregulates intracellular lipid metabolism and contributes to hepatic lipid deposition. Apolipoprotein J (ApoJ) is a molecular chaperone and participates in pathogen-induced and nutrient-induced lipid accumulation. This study investigates the mechanism of ApoJ-regulated ubiquitin-proteasomal degradation of mTOR, and a proof-of-concept ApoJ antagonist peptide is proposed to relieve hepatic steatosis. APPROACH AND RESULTS: By using omics approaches, upregulation of ApoJ was found in high-fat medium-fed hepatocytes and livers of patients with NAFLD. Hepatic ApoJ level associated with the levels of mTOR and protein markers of autophagy and correlated positively with lipid contents in the liver of mice. Functionally, nonsecreted intracellular ApoJ bound to mTOR kinase domain and prevented mTOR ubiquitination by interfering FBW7 ubiquitin ligase interaction through its R324 residue. In vitro and in vivo gain-of-function or loss-of-function analysis further demonstrated that targeting ApoJ promotes proteasomal degradation of mTOR, restores lipophagy and lysosomal activity, thus prevents hepatic lipid deposition. Moreover, an antagonist peptide with a dissociation constant (Kd) of 2.54 µM interacted with stress-induced ApoJ and improved hepatic pathology, serum lipid and glucose homeostasis, and insulin sensitivity in mice with NAFLD or type II diabetes mellitus. CONCLUSIONS: ApoJ antagonist peptide might be a potential therapeutic against lipid-associated metabolic disorders through restoring mTOR and FBW7 interaction and facilitating ubiquitin-proteasomal degradation of mTOR.

Evaluations of 3D-Printed Surgical Mask Tension Release Bands for Common COVID-19 Use with Biomechanics, Sensor Array System, and Finite Element Analysis.

A mask is one of the most basic protections to prevent the transmission of COVID-19. Surgical mask tension release bands (SMTRBs) are commonly used to ease the pain caused by prolonged mask use. However, the structural strength of SMTRBs and the effect that wearing masks with SMTRBs has on the face are unclear. Thus, this study assessed the mechanics of seven different types of 3D-printed SMTRBs. In this study, a tensile testing machine, a sensor array system, and finite element analysis were used to evaluate the mechanisms of seven SMTRBs. The tensile testing machine was applied to measure the breaking strength, elongation, stiffness, and rupture of the band. The sensor array system was used to calculate the pressure on the face when the band was used together with the mask. Finite element analysis was applied to evaluate the level of stress on the SMTRB structure when each of the seven bands was subjected to external force. The results demonstrated that thick SMTRBs put more pressure on the face but had greater structural strength. The thinner bands did not break easily; however, the mask ear loops tended to slip off more often. In addition, the size of the band hook affected the magnitude of the external force. This study provides a biomechanical reference for the future design of SMTRBs.

Chapter Open for the Excited-State Intramolecular Thiol Proton Transfer in the Room-Temperature Solution.

We report here, for the first time, the experimental observation on the excited-state intramolecular proton transfer (ESIPT) reaction of the thiol proton in room-temperature solution. This phenomenon is demonstrated by a derivative of 3-thiolflavone (3TF), namely, 2-(4-(diethylamino)phenyl)-3-mercapto-4H-chromen-4-one (3NTF), which possesses an -S-H···O═ intramolecular H-bond (denoted by the dashed line) and has an S1 absorption at 383 nm. Upon photoexcitation, 3NTF exhibits a distinctly red emission maximized at 710 nm in cyclohexane with an anomalously large Stokes shift of 12 230 cm-1. Upon methylation on the thiol group, 3MeNTF, lacking the thiol proton, exhibits a normal Stokes-shifted emission at 472 nm. These, in combination with the computational approaches, lead to the conclusion of thiol-type ESIPT unambiguously. Further time-resolved study renders an unresolvable (<180 fs) ESIPT rate for 3NTF, followed by a tautomer emission lifetime of 120 ps. In sharp contrast to 3NTF, both 3TF and 3-mercapto-2-(4-(trifluoromethyl)phenyl)-4H-chromen-4-one (3FTF) are non-emissive. Detailed computational approaches indicate that all studied thiols undergo thermally favorable ESIPT. However, once forming the proton-transferred tautomer, the lone-pair electrons on the sulfur atom brings non-negligible nπ* contribution to the S1' state (prime indicates the proton-transferred tautomer), for which the relaxation is dominated by the non-radiative deactivation. For 3NTF, the extension of π-electron delocalization by the diethylamino electron-donating group endows the S1' state primarily in the ππ* configuration, exhibiting the prominent tautomer emission. The results open a new chapter in the field of ESIPT, covering the non-canonical sulfur intramolecular H-bond and its associated ESIPT at ambient temperature.

Stemphylium Leaf Blight of Welsh Onion (Allium fistulosum): An Emerging Disease in Sanxing, Taiwan.

Welsh onion (Allium fistulosum L.) is one of the main and oldest vegetable crops grown in Taiwan. A severe epidemic of leaf blight in Welsh onion caused by a Stemphylium-like pathogen was found in Sanxing, Taiwan, from 2018 to 2020. However, correct species identification, biology, and control of Stemphylium leaf blight (SLB) of Welsh onion are not well-established. Therefore, the main objective of this study was to investigate the causal agent of SLB in Sanxing and evaluate the in vitro sensitivity of Stemphylium-like pathogen to commonly used fungicides. A phylogenetic analysis based on combining the internal transcribed spacer (ITS) region and glyceraldedyhe-3-phosphate dehydrogenase (gapdh) and calmodulin (cmdA) gene sequences together with morphological features identified that S. vesicarium is associated with SLB in Sanxing. When inoculated onto Welsh onion leaves, the isolates caused symptoms identical to those observed in the field; therefore, S. vesicarium was reisolated and Koch's postulates were confirmed. We observed a higher incidence of SLB symptoms on the oldest leaves compared with younger leaves. The maximum and minimum temperatures for in vitro mycelial growth and conidial germination (%) of S. vesicarium were 20 to 30°C and 5°C, respectively. Sixteen fungicides were tested for their effectiveness to reduce the mycelial growth and conidial germination of S. vesicarium in vitro. Boscalid plus pyraclostrobin, fluopyram, fluxapyroxad, and fluxapyroxad plus pyraclostrobin were highly effective at reducing mycelial growth and conidial germination in S. vesicarium. However, strobilurin fungicides (azoxystrobin and kresoxim-methyl) commonly used in Welsh onion production in Sanxing were ineffective. This study discusses the emergence of SLB caused by S. vesicarium in the foliar disease complex affecting Welsh onion and the management of the disease using fungicides with different modes of action in Taiwan. The research will support the sustainable management of SLB in Sanxing, Taiwan; however, further field assessments of the fungicides are warranted.

A survey of natal and neonatal teeth in newborn infants.

BACKGROUND/PURPOSE: Since there is no comprehensive research of natal and neonatal teeth in Taiwan, careful investigation of natal or neonatal teeth is worthy of being studied. This retrospective study investigated the prevalence and clinical characteristics of natal or neonatal teeth in a hospital setting, and analyzed the possible relationships between investigated variables of the natal or neonatal teeth. METHODS: All of the 12,019 infants born at an assigned hospital between January 1, 2008 and December 31, 2014 were investigated for natal or neonatal teeth. The identified individuals were reviewed for systemic diseases. Dental examinations included the location, clinical appearance, and degree of mobility. A positive family history of natal or neonatal teeth and mother's physical condition before delivery were also investigated. The collected data were analyzed using Fisher's exact test. RESULTS: Thirty infants were identified with a total of 43 natal or neonatal teeth (females, 19; males, 11). Most of the teeth were in the mandibular primary incisor position (97.6%). A radiographic examination confirmed that not all of the natal or neonatal teeth were supernumerary. No significant differences were observed between males and females in tooth morphology, positive family history, and treatment methods (p > 0.05) or between normal and conical shapes in positive family history, premature infant, mother's physical condition before delivery, and treatment methods (p > 0.05). CONCLUSION: Most of the natal or neonatal teeth were in the mandibular primary incisor position and not all of them were supernumerary. No gender differences were found in tooth morphology, positive family history, and treatment methods. The tooth morphology was not significantly related to a positive family history, premature delivery, or the mother's physical condition before delivery.

Biomechanical comparisons of F.E.R.I. techniques with different type of intramedullary screws fixation for Jones fractures.

Introduction: Jones fractures frequently fail to unite, and adequate fixation stability is crucial. This study aimed to elucidate the biomechanical stability of various intramedullary screw fixation constructs. Methods: Jones fracture model over the proximal 5th metatarsal of artificial bone was created in all specimens. Six groups were divided based on varied screw constructs with different screw lengths, either 30 or 40 mm, including cannulated screws-C30 and C40 groups, one high-resistance suture combined with intramedullary cannulated screws (F.E.R.I. technique)-CF30 and CF40 groups, and second-generation headless compression screws (SG-HCS) -HL30 and HL40 groups. Mechanical testing was conducted sequentially, and the maximal force (N) and stiffness (N/mm) of all constructs were recorded. Results: The maximal force (N) at 1.0 mm downward displacement in C30, C40, CF30, CF40, HL30, and HL40 groups were 0.56 ± 0.02, 0.49 ± 0.02, 0.65 ± 0.02, 0.49 ± 0.01, 0.68 ± 0.02, and 0.73 ± 0.02, respectively, and the stiffness (N/mm) in subgroups were 0.49 ± 0.01, 0.43 ± 0.01, 0.67 ± 0.01, 0.42 ± 0.01, 0.61 ± 0.01, and 0.58 ± 0.02, respectively. SG-HCS subgroups exhibited greater maximal force and stiffness than conventional cannulated screws. Screws of 30 mm in length demonstrated better stability than all 40 mm-length screws in each subgroup. In C30 fixation, the stiffness and maximum force endured increased by 1.16 and 1.12 times, respectively, compared with the C40 fixation method. There were no significant differences between CF30 and SG-HCS groups. Only the F.E.R.I technique combined with the 4.5 mm cannulated screw of 30 mm in length increased the biomechanical stability for Jones fractures. Discussion: These biomechanical findings help clinicians decide on better screw fixation options for greater stability in Jones fractures, especially when large-diameter screws are limited in use. However, this biomechanical testing of intramedullary screw fixation on Jones fracture model lacks clinical validation and no comparisons to extramedullary plate fixations. Moving forward, additional clinical and biomechanical research is necessary to validate our findings.

Prevention of Viral Hepatitis and HIV Infection among People Who Inject Drugs: A Systematic Review and Meta-Analysis.

This study aimed to explore the current evidence on preventing blood-borne virus infections among people who inject drugs (PWID). We conducted a comprehensive search across three databases (PubMed, Embase, Cochrane Library) for relevant articles published in English between 2014 and 2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) guidelines, assessed the quality of the paper using the revised Cochrane Risk of Bias Tool (ROB 2), and conducted a meta-analysis using RevMan 5.3. Completing the harm reduction program (HRP) participation and receiving all three vaccine doses resulted in a 28% reduction in the risk of HBV infection (OR: 0.72, 95% CI: 0.37-1.42). Various interventions increased the willingness of PWIDs to undergo HCV treatment (OR: 5.91, 95% CI: 2.46-14.24) and promoted treatment adherence (OR: 15.04, 95% CI: 2.80-80.61). Taking PrEP, participating in HRP, and modifying risky behaviors were associated with a 33% reduction in the risk of HIV infection (OR: 0.67, 95% CI: 0.61-0.74). Conducting referrals, providing counseling, and implementing antiretroviral therapy resulted in a 44% reduction in the risk of viral transmission (OR: 0.56, 95% CI: 0.47-0.66). Co-infection may potentially compromise effectiveness, so it is important to consider drug resistance.

Association of smoking cessation patterns and untreated smoking with glaucoma, cataract, and macular degeneration: a population-based retrospective study.

This study aims to assess the association between nicotine replacement therapy (NRT), varenicline, and untreated smoking with the risk of developing eye disorders. We employed a new-user design to investigate the association between NRT use and the incidence of eye disorders by the Taiwan National Health Insurance program. This study included 8416 smokers who received NRT and 8416 smokers who did not receive NRT (control group) matched using propensity scores between 2007 and 2018. After adjustment for relevant factors, a multivariable Cox regression analysis revealed that compared with untreated smokers, NRT use was associated with a significantly reduced risk of macular degeneration (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.13-0.87, P = 0.024). When stratified by dose, short-term NRT use (8-28 defined daily doses) was associated with significantly lower risk of glaucoma (HR: 0.35; 95% CI: 0.16-0.80, P = 0.012) and a trend toward reduced risk of cataract (HR: 0.60; 95% CI: 0.36-1.01, P = 0.053) compared to no treatment. However, these associations were not observed with long-term NRT use. The results of this real-world observational study indicate that NRT use, particularly short-term use, was associated with a lower risk of certain eye disorders compared to no treatment for smoking cessation. Long-term NRT use did not demonstrate the same benefits. Thus, short-term NRT may be a beneficial treatment strategy for reducing the risk of eye disorders in smokers attempting to quit. However, further evidence is required to verify these findings and determine the optimal duration of NRT use.

Comparing Cancer Risks and Mortality between Phytopharmaceuticals and Estrogen-Progestogen Medications for Menopausal Women: A Population-Based Cohort Study.

We evaluated the long-term risks of overall cancer and all-cause mortality associated with five types of phytopharmaceuticals and the most commonly used estrogen-progestogen medications for the treatment of postmenopausal syndrome in women. Using data from Taiwan's National Health Insurance Research Database (NHIRD) from 1 January 2000 to 31 December 2018, we conducted a 1:2 matched cohort study with 12,087 eligible patients. We compared phytopharmaceuticals -only users (n = 4029, phytopharmaceuticals group) with HRT-only users (n = 8058, HRT group) with a washout period of ≥6 months. The phytopharmaceuticals group had significantly lower risks of overall cancer and all-cause mortality than the HRT group (adjusted hazard ratio [95% confidence interval]: 0.60 [0.40-0.9] and 0.40 [0.16-0.99], respectively) after over 180 days of use. Bupleurum and Peony Formula were associated with lower risks of overall cancer and all-cause mortality (aHR: 0.57 [0.36-0.92] and 0.33 [0.11-1.05], respectively). In conclusion, phytopharmaceuticals may serve as an alternative therapy to HRT for alleviating menopausal symptoms and reducing health risks, leading to more favorable long-term health outcomes. Further randomized control trials are necessary to validate the findings of this study.

Optimizing Spinal Fusion Cage Design to Improve Bone Substitute Filling on Varying Disc Heights: A 3D Printing Study.

The success of spinal fusion surgery relies on the precise placement of bone grafts and minimizing scatter. This study aims to optimize cage design and bone substitute filling methods to enhance surgical outcomes. A 3D printed lumbar spine model was utilized to implant 3D printed cages of different heights (8 mm, 10 mm, 12 mm, and 14 mm) filled with BICERA® Bone Graft Substitute mixed with saline. Two filling methods, SG cage (side hole for grafting group, a specially designed innovative cage with side hole, post-implantation filling) and FP cage (finger-packing group, pre-implantation finger packing, traditional cage), were compared based on the weight of the implanted bone substitute. The results showed a significantly higher amount of bone substitute implanted in the SG cage group compared to the FP cage group. The quantity of bone substitute filled in the SG cage group increased with the height of the cage. However, in the FP cage group, no significant difference was observed between the 12 mm and 14 mm subgroups. Utilizing oblique lumbar interbody fusion cages with side holes for bone substitute filling after implantation offers several advantages. It reduces scatter and increases the amount of implanted bone substitute. Additionally, it effectively addresses the challenge of insufficient fusion surface area caused by gaps between the cage and endplates. The use of cages with side holes facilitates greater bone substitute implantation, ultimately enhancing the success of fusion. This study provides valuable insights for future advancements in oblique lumbar interbody fusion cage design, highlighting the effectiveness of using cages with side holes for bone substitute filling after implantation.

Hepatitis C virus inhibits DNA damage repair through reactive oxygen and nitrogen species and by interfering with the ATM-NBS1/Mre11/Rad50 DNA repair pathway in monocytes and hepatocytes.

Hepatitis C virus (HCV) infection is associated with the development of hepatocellular carcinoma and putatively also non-Hodgkin's B cell lymphoma. In this study, we demonstrated that PBMCs obtained from HCV-infected patients showed frequent chromosomal aberrations and that HCV infection of B cells in vitro induced enhanced chromosomal breaks and sister chromatid exchanges. HCV infection hypersensitized cells to ionizing radiation and bleomycin and inhibited nonhomologous end-joining repair. The viral core and nonstructural protein 3 proteins were shown to be responsible for the inhibition of DNA repair, mediated by NO and reactive oxygen species. Stable expression of core protein induced frequent chromosome translocations in cultured cells and in transgenic mice. HCV core protein binds to the NBS1 protein and inhibits the formation of the Mre11/NBS1/Rad50 complex, thereby affecting ATM activation and inhibiting DNA binding of repair enzymes. Taken together, these data indicate that HCV infection inhibits multiple DNA repair processes to potentiate chromosome instability in both monocytes and hepatocytes. These effects may explain the oncogenicity and immunological perturbation of HCV infection.

Long-term impact of certain coexisting extrahepatic unisystem and multisystem manifestations on trends in incidence of liver cirrhosis in treatment-naïve patients with chronic hepatitis C: A nested case-control study.

Diabetes mellitus (DM) was found to be more common in hepatitis C virus (HCV)-related cirrhotic males. However, the association between DM, or other extrahepatic manifestations (EHMs), and liver cirrhosis is still undetermined. We used a large-scale long-term study to analyze the cirrhosis risk of treatment-naïve HCV patients with EHMs as compared to those without. In this retrospective nested case-control study, we identified 11 872 treatment-naïve patients with chronic HCV between 2001 and 2013 from Taiwan National Health Insurance Research Database and divided them into patients with (cases) and without cirrhosis (controls). All patients were followed up from the index month (exact month of diagnosis) to the end of 2013, death, or study outcome, whichever occurred first. The cases and controls were 1:6 propensity score matched for age, sex, and exact month of diagnosis; finally, 8078 patients (1154 with and 6924 without cirrhosis) were included in the analysis. The presence of coexisting EHMs and a new diagnosis of cirrhosis was analyzed. Adjusted hazard ratios (HRs) and cumulative incidence for cirrhosis were calculated in conditional Cox regression models after propensity score matching. Patients with high-cirrhosis-risk EHMs, such as DM (HR: 1.72, 95% CI: 1.51-1.96, P < .001), HCD (HR: 1.45, 95% CI: 1.27-1.67, P < .007), CKD (HR: 1.21, 95% CI: 1.05-1.38, P < .001), hyperlipidemia (HR: 0.53, 95% CI: 0.46-0.60, P < .001), lichen planus (HR: 2.71, 95% CI: 1.56-4.72, P < .001), and palpable purpura (HR: 2.67, 95% CI: 2.13-3.35, P < .001) exhibited significantly higher risk of liver cirrhosis than those without. Cumulative incidence (P < .001) of liver cirrhosis by pairwise comparisons of multiple high-cirrhosis-risk EHMs, and that of lichen planus was the highest. Our study provided direct estimates of specific HCV-associated EHM time trends of cirrhosis risk, with an upward trend in incidence. Lichen planus was at the top of the list of single-EHM comparisons, and the maximum combination of certain EHMs was the greatest risk factor across a different array of multi-EHM comparisons for liver cirrhosis development.

Hormone replacement therapy is associated with reduced hepatocellular carcinoma risk and improved survival in postmenopausal women with hepatitis B: A nationwide long-term population-based cohort study.

Postmenopausal women with hepatitis B virus (HBV) infection are more likely to have accelerated liver fibrosis, eventually advancing to liver cirrhosis or hepatocellular carcinoma (HCC). The association between sex hormones and HBV-related HCC risk is unclear. We investigated whether hormone replacement therapy (HRT) is beneficial to postmenopausal women with HBV infection. This retrospective study selected the data of 44,465patients with HBV infection between January 2000 and December 2018 from Taiwan's National Health Insurance Research Database. After excluding patients with preexisting liver diseases, liver cirrhosis, or liver malignancies, we grouped the remaining 10,474 patients by whether they had undergone HRT for at least 3 months (n = 5,638) and whether they had not received HRT (n = 4,836). After propensity score matching, we assigned 3080 patients to an HRT cohort and matched them (1:1) with those in a non-HRT cohort. The incidence of HCC (P < 0.022) and all-cause mortality rate (P < 0.001) were lower in the HRT cohort than in the non-HRT cohort. The liver cirrhosis risk was not significantly higher in the HRT cohort (P = 0.355). HRT is associated with reduced HCC risk and improved survival outcomes but is unrelated to liver cirrhosis development in postmenopausal women.

Pharmacoepidemiological Research on N-Nitrosodimethylamine-Contaminated Ranitidine Use and Long-Term Cancer Risk: A Population-Based Longitudinal Cohort Study.

N-Nitrosodimethylamine (NDMA), a carcinogenic chemical, has recently been identified in ranitidine. We conducted a population-based study to explore ranitidine use and cancer emergence over time. Using the Taiwan National Health Insurance Research Database, a population-based cohort study was conducted. A total of 55,110 eligible patients who received ranitidine between January 2000 and December 2018 were enrolled in the treated cohort. We conducted a 1:1 propensity-score-matching procedure to match the ranitidine-treated group with the ranitidine-untreated group and famotidine controls for a longitudinal study. The association of ranitidine exposure with cancer outcomes was assessed. A multivariable Cox regression analysis that compared cancer risk with the untreated groups revealed that ranitidine increased the risk of liver (hazard ratio (HR): 1.22, 95% confidence interval (CI): 1.09-1.36, p < 0.001), lung (HR: 1.17, CI: 1.05-1.31, p = 0.005), gastric (HR: 1.26, CI: 1.05-1.52, p = 0.012), and pancreatic cancers (HR 1.35, CI: 1.03-1.77, p = 0.030). Our real-world observational study strongly supports the pathogenic role of NDMA contamination, given that long-term ranitidine use is associated with a higher likelihood of liver cancer development in ranitidine users compared with the control groups of non-ranitidine users treated with famotidine or proton-pump inhibitors.

Comparison of Emergency Room Visits and Rehospitalization for Bleeding Complications following Transurethral Procedures for the Treatment of Benign Prostatic Hyperplasia: A Population-Based Retrospective Cohort Study.

BACKGROUND: The postoperative bleeding complications associated with laser surgery of the prostate and transurethral resection of the prostate (TURP) were compared. METHODS: We used the Taiwan National Health Insurance Research Database to conduct an observational population-based cohort study. All eligible patients who received transurethral procedures between January 2015 and September 2018 were enrolled. Patients who received laser surgery or TURP were matched at a ratio of 1:1 by using propensity score matching, and the association of these procedures with bleeding events was evaluated. RESULTS: A total of 3302 patients who underwent elective transurethral procedures were included. The multivariable Cox regression analysis revealed that diode laser enucleation of the prostate (DiLEP) resulted in significantly higher emergency room risks within 90 days after surgery due to clot retention than the Monopolar transurethral resection of the prostate (M-TURP) (Hazard Ratio: 1.52; 95% Confidence Interval [CI], 1.06-2.16, p = 0.022). Moreover, GreenLight photovaporization of the prostate (PVP) (0.61; 95% CI, 0.38-1.00 p = 0.050) and thulium laser vaporesection of the prostate (ThuVARP) (0.67; 95% CI, 0.47-0.95, p = 0.024) resulted in significantly fewer rehospitalization due to clot retention than did M-TURP. No significant increase in blood clots were observed in patients using comedications and those with different demographic characteristics and comorbidities. CONCLUSIONS: Among the investigated six transurethral procedures for Benign prostatic hyperplasia, PVP and ThuVARP were safer than M-TURP because bleeding events and clot retention were less likely to occur, even in patients receiving anticoagulant or antiplatelet therapy. However, DiLEP and holmium laser enucleation of the prostate (HoLEP) did not result in fewer bleeding events than M-TURP.

Tuning intramolecular charge transfer and spin-orbit coupling of AIE-active type-I photosensitizers for photodynamic therapy.

Development of photosensitizers (PSs) featuring type-I reactive oxygen species (ROS) with aggregation-induced emission (AIE) properties is a judicious approach to overcome the deficit of conventional photodynamic therapy (PDT). However, it remains a challenge to design AIE-active type-I ROS PSs using a simple theranostic scaffold paired with a delicate balance between intramolecular charge transfer (ICT) and large spin-orbit coupling (SOC) features to facilitate intersystem crossing (ISC) and hence to intensify triplet excitons for type-I ROS generation as well as to improve optical properties for the desired biomedical applications. In this work, a rationally designed series of PSs based on C-6-substituted tetraphenylethylene-fused benzothiazole-coumarin scaffolds, named TPE-nCUMs, were synthesized via a fused-ring-electron-acceptor (FREA) strategy, endowed with AIE properties in aqueous solution and thus self-monitoring type-I ROS generation under white-light irradiation to study the effects of diverse ICT and SOC potentials on their photochemical and optical properties. Both experimental and theoretical results revealed that the concomitantly increasing strengths of both ICT and SOC features promote type-I ROS generation by TPE-nCUMs. The key role of the SOC-promoting carbonyl group towards the ROS generation ability of TPE-nCUMs was then examined. Among TPE-nCUMs, gem-2OMe-TPE-2CUM displayed highly efficient type-I ROS generation. Importantly, gem-OMe-TPE-1CUM acts as a fluorescent indicator in HeLa cells (in vitro), revealing its excellent diffusion capability in both lysosomal and mitochondrial organelles with low dark toxicity, high cytotoxicity under white-light and remarkable PDT efficiency. Our study has thus elucidated a rationally designed strategy at the molecular level to fine-tune ICT and SOC features for the advance of AIE-active type-I ROS PSs, opening a new avenue for cancer treatment and image-guided therapy.

Assessment of ELISA-based method for the routine examination of serum indoxyl sulfate in patients with chronic kidney disease.

Introduction: Indoxyl sulfate (IS), a protein-bound uremic toxin, is associated with kidney function and chronic kidney disease (CKD)-related complications. Currently, serum IS levels are primarily quantified using mass spectrometry-based methods, which are not feasible for routine clinical examinations. Methods: The efficiencies of three commercial ELISA kits in determination of serum IS were validated by comparing with ultra-performance liquid chromatography (UPLC)-MS/MS-based method using Bland-Altman analysis. The associations between kidney parameters and serum IS levels determined by ELISA kit from Leadgene and UPLC-MS/MS were evaluated by Spearman correlation coefficient in a CKD validation cohort. Results: ELISA kit from Leadgene showed clinical agreement with UPLC-MS/MS in the determination of serum IS levels (p = 0.084). In patients with CKD, Spearman's correlation analysis revealed a perfect correlation between the IS levels determined using the Leadgene ELISA kit and UPLC-MS/MS (r = 0.964, p < 0.0001). IS levels determined using the Leadgene ELISA kit were associated with the estimated glomerular filtration rate (r = -0.772, p < 0.0001) and serum creatinine concentration (r = 0.824, p < 0.0001) in patients with CKD, and on dialysis (r = 0.557, p = 0.006). Conclusions: The Leadgene ELISA kit exhibits comparable efficacy to UPLC-MS/MS in quantifying serum IS levels, supporting that ELISA would be a personalized method for monitoring the dynamic changes in serum IS levels in dialysis patients to prevent the progression of CKD.

A cohort study to investigate hepatocellular carcinoma risk in hepatitis C patients.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) frequently occurs with chronic hepatitis C (HCV) infection. This study tried to identify clinical and laboratory factors affecting development of HCC in a longitudinal follow-up of chronic HCV patients. METHODOLOGY: A total of 373 patients with CHC who were HCV RNA-seropositive were recruited during 2000-2003. The remaining 164 patients after application of exclusion criteria (90 males; 74 females; mean age: 58.2 +/- 14y/o) were prospectively recruited and followed-up with periodic liver function tests, alfa-fetoprotein and abdominal ultrasound examinations. RESULTS: During follow-up between January 2000 and May 2008, HCC was identified in 19 (11.6%) patients. The incidence rate of HCC was 14.5/1,000 person-years. Fifteen patients (9.1%) developed a cirrhotic liver. Male gender (p=0.018), genotype 1b (p=0.034), cirrhosis (p<0.001) and older age (> or = 65y/o) (p=0.02) are significant risk factors for HCC. Overall, there was 2.7-fold increased risk in patients with HCV RNA > or = 1 million copies/mL to develop HCC. The incidence rate of HCC was 8.8% for pegIFNa/RBV-treated patients with sustained viral response and 14.3% for untreated patients (p=0.352). CONCLUSIONS: This cohort study highlights the roles of male gender, older age and genotype 1b in the progression from chronic HCV to HCC in an area endemic for hepatitis B.

Sterol O-acyltransferase 2 chaperoned by apolipoprotein J facilitates hepatic lipid accumulation following viral and nutrient stresses.

The risks of non-alcoholic fatty liver disease (NAFLD) include obese and non-obese stresses such as chronic hepatitis C virus (HCV) infection, but the regulatory determinants remain obscure. Apolipoprotein J (ApoJ) served as an ER-Golgi contact-site chaperone near lipid droplet (LD), facilitating HCV virion production. We hypothesized an interplay between hepatic ApoJ, cholesterol esterification and lipid deposit in response to NAFLD inducers. Exposures of HCV or free-fatty acids exhibited excess LDs along with increased ApoJ expression, whereas ApoJ silencing alleviated hepatic lipid accumulation. Both stresses could concomitantly disperse Golgi, induce closer ApoJ and sterol O-acyltransferase 2 (SOAT2) contacts via the N-terminal intrinsically disordered regions, and increase cholesteryl-ester. Furthermore, serum ApoJ correlated positively with cholesterol and low-density lipoprotein levels in normal glycaemic HCV patients, NAFLD patients and in mice with steatosis. Taken together, hepatic ApoJ might activate SOAT2 to supply cholesteryl-ester for lipid loads, thus providing a therapeutic target of stress-induced steatosis.