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Background/Objectives: Primary dysmenorrhea (PD) is a common condition affecting up to 90% of menstruating women, which often results in significant pain without an underlying pathology. Zinc, recognized for its anti-inflammatory and antioxidant effects through inhibiting prostaglandin production and superoxide dismutase 1 (SOD1) upregulation, alleviates menstrual pain by preventing uterine spasms and enhancing microcirculation in the endometrium, suggesting its potential as an alternative treatment for primary dysmenorrhea. The goal of this systematic review and meta-analysis was to assess the efficacy and safety of zinc supplementation in reducing pain severity among women with PD and to explore the influence of dosage and treatment duration. Methods: Following the PRISMA 2020 guidelines, we conducted an extensive search across databases such as PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar, up to May 2024. Randomized controlled trials assessing the effects of zinc supplementation on pain severity in women with PD were included. Pain severity was evaluated with established tools, such as the Visual Analog Scale (VAS). Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) tool. Two reviewers independently performed the data extraction, and a random-effects model was used for meta-analysis. Meta-regressions were conducted to examine the influence of zinc dosage and treatment duration on pain reduction. Adverse events were also analyzed. Results: Six RCTs involving 739 participants met the inclusion criteria. Zinc supplementation significantly reduced pain severity compared to placebo (Hedges's g = −1.541; 95% CI: −2.268 to −0.814; p < 0.001), representing a clinically meaningful reduction in pain. Meta-regression indicated that longer treatment durations (≥8 weeks) were associated with greater pain reduction (p = 0.003). While higher zinc doses provided additional pain relief, the incremental benefit per additional milligram was modest (regression coefficient = −0.02 per mg; p = 0.005). Adverse event rates did not differ significantly between the zinc and placebo groups (odds ratio = 2.54; 95% CI: 0.78 to 8.26; p = 0.122), suggesting good tolerability. Conclusions: Zinc supplementation is an effective and well-tolerated option for reducing pain severity in women with primary dysmenorrhea. Doses as low as 7 mg/day of elemental zinc are sufficient to achieve significant pain relief, with longer durations (≥8 weeks) enhancing efficacy. The favorable safety profile and ease of use support the consideration of zinc supplementation as a practical approach to managing primary dysmenorrhea. [ABSTRACT FROM AUTHOR]

A 6T1C pixel circuit based on low-temperature polycrystalline oxide (LTPO) technology for portable active-matrix organic light-emitting diode (AMOLED) display applications is proposed in this paper. For superior high-end portable applications including 4K high resolution and high PPI (pixels per inch), the proposed pixel circuit employs a single storage capacitor and signal sharing switch-control design and provides low-voltage driving and immunity to the IR-drop issue and OLED degradation. Furthermore, the threshold voltage and mobility-compensating capabilities are improved by both compensation mechanisms, which are based on a negative feedback system, and mobility-related compensation parameters. Simulation results reveal that threshold voltage variations of ±0.33 V in the driving thin-film transistors can be well sensed and compensated while the maximum OLED current shift is 4.25%. The maximum variation in OLED currents within all gray levels is only 1.05% with mobility variations of ±30%. As a result, the proposed 6T1C pixel circuit is a good candidate for portable AMOLED display usage. [ABSTRACT FROM AUTHOR]

Neurogenic lower urinary tract dysfunction, common in patients with chronic spinal cord injury, inevitably results in urological complications. To address neurogenic lower urinary tract dysfunction after spinal cord injury, proper and adequate bladder management is important in spinal cord injury rehabilitation, with the goal and priorities of the protection of upper urinary tract function, maintaining continence, preserving lower urinary tract function, improvement of SCI patients' quality of life, achieving compatibility with patients' lifestyles, and decreasing urological complications. This concise review aims to help urologists address neurogenic lower urinary tract dysfunction by focusing on the risks of long-term urological complications and the effects of different bladder management strategies on these complications based on scientifically supported knowledge. [ABSTRACT FROM AUTHOR]

This paper proposes a new 6T1C pixel circuit based on low-temperature polycrystalline oxide (LTPO) technology for portable active-matrix organic light-emitting diode (AMOLED) displays with variable refresh rates ranging from 1 to 120 Hz. The proposed circuit has a simple structure and is based on the design of sharing lines of switch-controlling signals. It also provides low-voltage driving and immunity to OLED degeneration issues. The calculation and analysis of programming time are discussed, and the optimal storage capacitor for the proposed circuit's high-speed driving is selected. The results of the simulation reveal that threshold voltage variations in driving thin-film transistors of ±0.33 V can be well sensed and compensated with a 1.8% average shift of OLED currents in high-frame-rate operation (120 Hz), while the maximum variation in OLED currents within all gray levels is only 3.56 nA in low-frame-rate operation (1 Hz). As a result, the proposed 6T1C pixel circuit is a good candidate for use in portable AMOLED displays. [ABSTRACT FROM AUTHOR]

The clinical efficacy of adjuvant chemotherapy in upper tract urothelial carcinoma (UTUC) is unclear. We aimed to assess the therapeutic outcomes of adjuvant chemotherapy in patients with advanced UTUC (pT3-T4) after radical nephroureterectomy (RNU). We retrospectively reviewed the data of 2108 patients from the Taiwan UTUC Collaboration Group between 1988 and 2018. Comprehensive clinical features, pathological characteristics, and survival outcomes were recorded. Univariate and multivariate Cox proportional hazards models were used to evaluate overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Of the 533 patients with advanced UTUC included, 161 (30.2%) received adjuvant chemotherapy. In the multivariate analysis, adjuvant chemotherapy was significantly associated with a reduced risk of overall death (hazard ratio (HR), 0.599; 95% confidence interval (CI), 0.419–0.857; p = 0.005), cancer-specific mortality (HR, 0.598; 95% CI, 0.391–0.914; p = 0.018), and cancer recurrence (HR, 0.456; 95% CI, 0.310–0.673; p < 0.001). The Kaplan–Meier survival analysis revealed that patients receiving adjuvant chemotherapy had significantly better five-year OS (64% vs. 50%, p = 0.002), CSS (70% vs. 62%, p = 0.043), and DFS (60% vs. 48%, p = 0.002) rates compared to those who did not receive adjuvant chemotherapy. In conclusion, adjuvant chemotherapy after RNU had significant therapeutic benefits on OS, CSS, and DFS in advanced UTUC. [ABSTRACT FROM AUTHOR]

Chronic partial bladder outlet obstruction (PBOO) is a prevalent clinical problem that may result from multiple etiologies. PBOO may be a secondary condition to various anatomical and functional abnormalities. Bladder fibrosis is the worst outcome of PBOO. However, gene alterations and the mechanism of fibrosis development after PBOO onset are not clear. Therefore, we aimed to investigate gene expression alterations during chronic PBOO. A rat model of PBOO was established and validated by a significant increase in rat bladder weight. The bladder samples were further analyzed by microarray, and differentially expressed genes (DEGs) that are more related to PBOO compared with the control genes were selected. The data showed that 16 significantly upregulated mRNAs and 3 significantly downregulated mRNAs are involved in fibrosis. Moreover, 13 significantly upregulated mRNAs and 12 significantly downregulated mRNAs are related to TGFB signaling. Twenty-two significantly upregulated mRNAs and nine significantly downregulated mRNAs are related to the extracellular matrix. The genes with differential expressions greater than four-fold included Grem1, Thbs1, Col8a1, Itga5, Tnc, Lox, Timp1, Col4a1, Col4a2, Bhlhe40, Itga1, Tgfb3, and Gadd45b. The gene with a differential expression less than a quarter-fold was Thbs2. These findings show the potential roles of these genes in the physiology of PBOO. [ABSTRACT FROM AUTHOR]

A new low-frame-rate active-matrix organic light-emitting diode (AMOLED) pixel circuit with low-temperature poly-Si and oxide (LTPO) thin-film transistors (TFTs) for portable displays with high pixel density is reported. The proposed pixel circuit has the excellent ability to compensate for the threshold voltage variation of the driving TFT (ΔVTH_DTFT). By the results of simulation based on a fabricated LTPS TFT and a-IZTO TFT, we found that the error rates of the OLED current were all lower than 2.71% over the range of input data voltages when ΔVTH_DTFT = ±0.33 V, and a low frame rate of 1 Hz could be achieved with no flicker phenomenon. Moreover, with only one capacitor and two signal lines in the pixel circuit, a high pixel density and narrow bezel are expected to be realized. We revealed that the proposed 7T1C pixel circuit with low driving voltage and low frame rate is suitable for portable displays. [ABSTRACT FROM AUTHOR]

Background and Objectives: ABO blood types have been implicated as potential risk factors for various hemorrhagic diseases. No study has investigated the association between gastroesophageal variceal bleeding and ABO blood types. We aimed to evaluate the impact of ABO blood types on mortality and bleeding risk in acute gastroesophageal variceal bleeding. Materials and Methods: This is a retrospective observational study. Patients presenting with acute gastroesophageal varices bleeding diagnosed by endoscopy were enrolled, and were divided by blood type into a type O group and non-type O group. The outcomes were death within 30 days and the proportion of further bleeding. We used generalized linear mixed-effects models to analyze the outcomes. Results: A total of 327 patients and 648 records of emergency room visits were included. The 30-day mortality was 14.8% (21 of 142 patients) in the type O group, and 16.2% (30 of 185 patients) in the non-type O group (p = 0.532). Further bleeding within 30 days occurred in 34 cases (12.6%) in the type O group, and in 26 cases (6.9%) in the non-type O group (p = 0.539). Conclusions: There was no significant difference in blood transfusion volume in 24 h, recurrent bleeding rates, or mortality between patients with blood type O and those with non-type O. [ABSTRACT FROM AUTHOR]

The urothelium displays mechano- and chemosensory functions via numerous receptors and channels. The calcium-sensing receptor (CaSR) detects extracellular calcium and modulates several physiological functions. Nonetheless, information about the expression and the role of CaSR in lower urinary tract has been absent. We aimed to determine the existence of urothelial CaSR in urinary bladder and its effect on micturition function. We utilized Western blot to confirm the expression of CaSR in bladder and used immunofluorescence to verify the location of the CaSR in the bladder urothelium via colocalization with uroplakin III A. The activation of urothelial CaSR via the CaSR agonist, AC-265347 (AC), decreased urinary bladder smooth muscle (detrusor) activity, whereas its inhibition via the CaSR antagonist, NPS-2143 hydrochloride (NPS), increased detrusor activity in in vitro myography experiments. Cystometry, bladder nerve activities recording, and bladder surface microcirculation detection were conducted to evaluate the effects of the urothelial CaSR via intravesical administrations. Intravesical AC inhibited micturition reflex, bladder afferent and efferent nerve activities, and reversed cystitis-induced bladder hyperactivity. The urothelial CaSR demonstrated a chemosensory function, and modulated micturition reflex via regulating detrusor activity. This study provided further evidence of how the urothelial CaSR mediated micturition and implicated the urothelial CaSR as a potential pharmacotherapeutic target in the intervention of bladder disorders. [ABSTRACT FROM AUTHOR]

In this study, we investigated the effect of mTOR inhibitor (mTORi) drug-eluting biodegradable stent (DE stent), a putative restenosis-inhibiting device for coronary artery, on thermal-injury-related ureteral stricture in rabbits. In vitro evaluation confirmed the dose-dependent effect of mTORi, i.e., rapamycin, on fibrotic markers in ureteral component cell lines. Upper ureteral fibrosis was induced by ureteral thermal injury in open surgery, which was followed by insertion of biodegradable stents, with or without rapamycin drug-eluting. Immunohistochemistry and Western blotting were performed 4 weeks after the operation to determine gross anatomy changes, collagen deposition, expression of epithelial–mesenchymal transition markers, including Smad, α-SMA, and SNAI 1. Ureteral thermal injury resulted in severe ipsilateral hydronephrosis. The levels of type III collagen, Smad, α-SMA, and SNAI 1 were increased 28 days after ureteral thermal injury. Treatment with mTORi-eluting biodegradable stents significantly attenuated thermal injury-induced urinary tract obstruction and reduced the level of fibrosis proteins, i.e., type III collagen. TGF-β and EMT signaling pathway markers, Smad and SNAI 1, were significantly modified in DE stent-treated thermal-injury-related ureteral stricture rabbits. These results suggested that intra-ureteral administration of rapamycin by DE stent provides modification of fibrosis signaling pathway, and inhibiting mTOR may result in fibrotic process change. [ABSTRACT FROM AUTHOR]

In this study, the anti-proliferative effect of ilimaquinone, a sesquiterpene derivative from the marine sponge, in breast cancer cells was investigated. Ilimaquinone inhibited the proliferation of MCF-7 and MDA-MB-231 breast cancer cells with IC50 values of 10.6 μM and 13.5 μM, respectively. Non-tumorigenic human breast epithelial cells were less sensitive to ilimaquinone than breast cancer cells. Flow cytometric and Western blot analysis showed that ilimaquinone induced S-phase arrest by modulating the expression of p-CDC-2 and p21. Ilimaquinone induces apoptosis, which is accompanied by multiple biological biomarkers, including the downregulation of Akt, ERK, and Bax, upregulation of p38, loss of mitochondrial membrane potential, increased reactive oxygen species generation, and induced autophagy. Collectively, these findings suggest that ilimaquinone causes cell cycle arrest as well as induces apoptosis and autophagy in breast cancer cells. [ABSTRACT FROM AUTHOR]

We sought to examine the effect of tumor location on the prognosis of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). This retrospective study came from the Taiwan UTUC Collaboration Group, which consisted of 2658 patients at 15 institutions in Taiwan from 1988 to 2019. Patients with kidney-sparing management, both renal pelvic and ureteral tumors, as well as patients lacking complete data were excluded; the remaining 1436 patients were divided into two groups: renal pelvic tumor (RPT) and ureteral tumor (UT), with 842 and 594 patients, respectively. RPT was associated with more aggressive pathological features, including higher pathological T stage (p < 0.001) and the presence of lymphovascular invasion (p = 0.002), whereas patients with UT often had synchronous bladder tumor (p < 0.001), and were more likely to bear multiple lesions (p = 0.001). Our multivariate analysis revealed that UT was a worse prognostic factor compared with RPT (overall survival: HR 1.408, 95% CI 1.121–1.767, p = 0.003; cancer-specific survival: HR 1.562, 95% CI 1.169–2.085, p = 0.003; disease-free survival: HR 1.363, 95% CI 1.095–1.697, p = 0.006; bladder-recurrence-free survival: HR 1.411, 95% CI 1.141–1.747, p = 0.002, respectively). Based on our findings, UT appeared to be more malignant and had a worse prognosis than RPT. [ABSTRACT FROM AUTHOR]

We recently isolated a cardiac glycoside (CG), αldiginoside, from an indigenous plant in Taiwan, which exhibits potent tumor-suppressive efficacy in oral squamous cell carcinoma (OSCC) cell lines (SCC2095 and SCC4, IC50 < 0.2 µM; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays). Here, we report that αldiginoside caused Sphase arrest and apoptosis, through the inhibition of a series of signaling pathways, including those mediated by cyclin E, phospho-CDC25C (p-CDC25C), and janus kinase/signal transducer and activator of transcription (JAK/STAT)3. αldiginoside induced apoptosis, as indicated by caspase activation and poly (ADP-ribose) polymerase (PARP) cleavage. Equally important, αldiginoside reduced Mcl-1 expression through protein degradation, and overexpression of Mcl-1 partially protected SCC2095 cells from αldiginoside's cytotoxicity. Taken together, these data suggest the translational potential of αldiginoside to foster new therapeutic strategies for OSCC treatment. [ABSTRACT FROM AUTHOR]

In recent years, active-matrix organic light-emitting diodes (AMOLEDs) has been the most popular display for portable application. To satisfy the requirement for the application of the portable display, the design of the compensating pixel circuit with the low-voltage driving and low-power consumption will be requested. In addition to the circuit with the design of the low-voltage driving, high-mobility thin-film transistors as driving device will be also necessary in order to supply larger driving current at low-voltage driving. Therefore, the study presents a new low-voltage driving AMOLED pixel circuit with high-mobility amorphous indium–zinc–tin–oxide (a-IZTO) thin-film transistors (TFTs) as driving device for portable displays with high resolution. The proposed pixel circuit can simultaneously compensate for the threshold voltage variation of driving TFT (ΔVTH_TFT), OLED degradation (ΔVTH_OLED), and the I-R drop of a power line (ΔVDD). By using AIM-Spice for simulation based on fabricated a-IZTO TFTs with mobility of 70 cm2V−1S−1 as driving devices, we discovered that the error rates of the driving current were all lower than 5.71% for all input data when ΔVTH_TFT = ±1 V, ΔVDD = 0.5 V, and ΔVTH_OLED = 0.5 V were all considered simultaneously. We revealed that the proposed 5T2C pixel circuit containing a high-mobility a-IZTO TFT as a driving device was suitable for high-resolution portable displays. [ABSTRACT FROM AUTHOR]

In this study, the anti-tumor activity of ilimaquinone (IQ), a sesquiterpene quinone isolated from marine sponge Halichondria sp., in oral squamous cell carcinoma (OSCC) cells, was investigated. IQ suppressed the viability of the OSCC cell lines SCC4 and SCC2095 with IC50 values of 7.5 and 8.5 μM, respectively. Flow cytometric analysis demonstrated that IQ induced caspase-dependent apoptosis in SCC4 cells and modulated the expression of several cell growth-related gene products, including Akt, p38, Mcl-1, and p53. Notably, p53 knockdown caused higher resistance to IQ's anti-tumor activity. In addition, IQ increased reactive oxygen species generation, which was partially reversed by the addition of antioxidants. Furthermore, it triggered autophagy, as evidenced by acidic organelle formation and LC3B-II and Atg5 expression in SCC4 cells. Pretreatment with the autophagy inhibitor 3-methyladenine or chloroquine partially decreased IQ-induced apoptosis, suggesting that IQ induced protective autophagy. In summary, IQ has potential to be used in OSCC therapy. [ABSTRACT FROM AUTHOR]

Non-bacterial prostatitis is an inflammatory disease that is difficult to treat. Oligonucleotide aptamers are well known for their stability and flexibility in conjugating various inflammatory molecules. In this study, we investigated the effects of inflammatory cytokine-targeting aptamers (ICTA), putative neutralizers of TNF-alpha and IL-1 beta activation, on local carrageenan-induced prostate inflammation, allodynia, and hyperalgesia in rats. In vitro evaluation confirmed the binding capability of ICTA. Intraprostatic injection of carrageenan or control vehicle was performed in six-week-old rats, and ICTA (150 µg) or vehicle was administered in the prostate along with carrageenan injection. The von Frey filament test was performed to determine mechanical allodynia, and prostate inflammation was examined seven days after drug administration. Local carrageenan administration resulted in a reduction of the tactile threshold. The levels of mononuclear cell infiltration, pro-inflammatory cytokine interleukin-1 beta (b), caspase-1 (casp-1), and Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing proteins 1 and 3 (NALP1 and NALP3) in the prostate of rats were increased seven days after carrageenan injection. Treatment with ICTA significantly attenuated the carrageenan-induced hyperalgesia and reduced the elevated levels of proteins including TNF-a and IL-1b in the rats. Apoptosis markers, B-cell lymphoma 2-associated X protein (Bax) and caspase-3, were elevated in ICTA-treated Chronic pelvic pain syndrome (CPPS) rats. These results suggest that ICTA provides protection against local carrageenan-induced enhanced pain sensitivity, and that the neutralization of proinflammatory cytokines may result in inflammatory cell apoptosis. [ABSTRACT FROM AUTHOR]

Autophagy is an evolutionarily conserved pathway to degrade damaged proteins and organelles for subsequent recycling in cells during times of nutrient deprivation. This process plays an important role in tumor development and progression, allowing cancer cells to survive in nutrient-poor environments. The plant kingdom provides a powerful source for new drug development to treat cancer. Several plant extracts induce autophagy in cancer cells. However, little is known about the role of plant extracts in autophagy inhibition, particularly autophagy-related (ATG) proteins. In this study, we employed S-tagged gamma-aminobutyric acid receptor associated protein like 2 (GABARAPL2) as a reporter to screen 48 plant extracts for their effects on the activity of autophagy protease ATG4B. Xanthium strumarium and Tribulus terrestris fruit extracts were validated as potential ATG4B inhibitors by another reporter substrate MAP1LC3B-PLA2. The inhibitory effects of the extracts on cellular ATG4B and autophagic flux were further confirmed. Moreover, the plant extracts significantly reduced colorectal cancer cell viability and sensitized cancer cells to starvation conditions. The fruit extract of X. strumarium consistently diminished cancer cell migration and invasion. Taken together, the results showed that the fruit of X. strumarium may have an active ingredient to inhibit ATG4B and suppress the proliferation and metastatic characteristics of colorectal cancer cells. [ABSTRACT FROM AUTHOR]

Myoporum bontioides is a traditional medicinal plant in Asia with various biological activities, including anti-inflammatory and anti-bacterial characteristics. To identify the bioactive constituents from M. bontioides, a newly-identified flavone, 3,4'-dimethoxy-3',5,7-trihydroxyflavone (compound 1), along with eight known compounds, were investigated in human MCF-7 breast cancer, SCC4 oral cancer, and THP-1 monocytic leukemia cells. Among these compounds, compound 1 exhibited the strongest antiproliferative activity with half-maximal inhibitory concentration (IC 50 ) values ranging from 3.3 μM (MCF-7) to 8.6 μM (SCC4). Flow cytometric analysis indicated that compound 1 induced G2/M cell cycle arrest in MCF-7 cells. Mechanistic evidence suggests that the G2/M arrest could be attributable to compound 1's modulatory effects on the phosphorylation and expression of numerous key signaling effectors, including cell division cycle 2 (CDC2), CDC25C, and p53. Notably, compound 1 downregulated the expression of histone deacetylase 2 (HDAC2) and HDAC4, leading to increased histone H3 acetylation and p21 upregulation. Together, these findings suggest the translational potential of compound 1 as a breast cancer treatment.