Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

Alterations in coenzyme Q10 status in a cybrid line harboring the 3243A>G mutation of mitochondrial DNA is associated with abnormal mitochondrial bioenergetics and dysregulated mitochondrial biogenesis.

Mitochondrial DNA (mtDNA) mutations, including the m.3243A>G mutation that causes mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), are associated with secondary coenzyme Q10 (CoQ10) deficiency. We previously demonstrated that PPARGC1A knockdown repressed the expression of PDSS2 and several COQ genes. In the present study, we compared the mitochondrial function, CoQ10 status, and levels of PDSS and COQ proteins and genes between mutant cybrids harboring the m.3243A>G mutation and wild-type cybrids. Decreased mitochondrial energy production, defective respiratory function, and reduced CoQ10 levels were observed in the mutant cybrids. The ubiquinol-10:ubiquinone-10 ratio was lower in the mutant cybrids, indicating blockage of the electron transfer upstream of CoQ, as evident from the reduced ratio upon rotenone treatment and increased ratio upon antimycin A treatment in 143B cells. The mutant cybrids exhibited downregulation of PDSS2 and several COQ genes and upregulation of COQ8A. In these cybrids, the levels of PDSS2, COQ3-a isoform, COQ4, and COQ9 were reduced, whereas those of COQ3-b and COQ8A were elevated. The mutant cybrids had repressed PPARGC1A expression, elevated ATP5A levels, and reduced levels of mtDNA-encoded proteins, nuclear DNA-encoded subunits of respiratory enzyme complexes, MNRR1, cytochrome c, and DHODH, but no change in TFAM, TOM20, and VDAC1 levels. Alterations in the CoQ10 level in MELAS may be associated with mitochondrial energy deficiency and abnormal gene regulation. The finding of a reduction in the ubiquinol-10:ubiquinone-10 ratio in the MELAS mutant cybrids differs from our previous discovery that cybrids harboring the m.8344A>G mutation exhibit a high ubiquinol-10:ubiquinone-10 ratio.

Real-World Clinical Performance of a Novolimus-Eluting Stent Versus a Sirolimus-Eluting Stent.

INTRODUCTION: The DESyne novolimus-eluting coronary stent (NES) is a new-generation drug-eluting stent (DES) that is widely used, but clinical data are rarely reported for this stent. We compared the safety and effectiveness of the DESyne NES and the Orsiro bioresorbable polymer sirolimus-eluting stent (SES) in patients undergoing percutaneous coronary intervention (PCI). METHODS: This was a retrospective, single-center, observational study. Between July 2017 and December 2022, patients who presented with chronic or acute coronary syndrome undergoing PCI with DESyne NES or Orsiro SES were consecutively enrolled in the present study. The primary endpoint, major adverse cardiovascular event (MACE), was a composite of cardiovascular death, target-vessel myocardial infarction, or clinically driven target-lesion revascularization. RESULTS: A total of 776 patients (age 68.8 ± 12.2; 75.9% male) undergoing PCI were included. Overall, 231 patients with 313 lesions received NES and 545 patients with 846 lesions received SES. During a follow-up duration of 784 ± 522 days, the primary endpoint occurred in 10 patients (4.3%) in the NES group and in 36 patients (6.6%) in the SES group. After multivariate adjustment, the risk of MACE did not significantly differ between groups (NES vs. SES, hazard ratio 0.74, 95% CI, 0.35-1.55, p = 0.425). The event rate of individual components of the primary endpoint was comparable between the two groups. CONCLUSIONS: Favorable and similar clinical outcomes were observed in patients undergoing PCI with either NES or SES in a medium-term follow-up duration. Future studies with adequately powered clinical endpoints are required for further evaluation.

C-X-C motif chemokine ligand 12-C-X-C chemokine receptor type 4 signaling axis in cancer and the development of chemotherapeutic molecules.

Chemokines are small, secreted cytokines crucial in the regulation of a variety of cell functions. The binding of chemokine C-X-C motif chemokine ligand 12 (CXCL12) (stromal cell-derived factor 1) to a G-protein-coupled receptor C-X-C chemokine receptor type 4 (CXCR4) triggers downstream signaling pathways with effects on cell survival, proliferation, chemotaxis, migration, and gene expression. Intensive and extensive investigations have provided evidence suggesting that the CXCL12-CXCR4 axis plays a pivotal role in tumor development, survival, angiogenesis, metastasis, as well as in creating tumor microenvironment, thus implying that this axis is a potential target for the development of cancer therapies. The structures of CXCL12 and CXCR4 have been resolved with experimental methods such as X-ray crystallography, NMR, or cryo-EM. Therefore, it is possible to apply structure-based computational approaches to discover, design, and modify therapeutic molecules for cancer treatments. Here, we summarize the current understanding of the roles played by the CXCL12-CXCR4 signaling axis in cellular functions linking to cancer progression and metastasis. This review also provides an introduction to protein structures of CXCL12 and CXCR4 and the application of computer simulation and analysis in understanding CXCR4 activation and antagonist binding. Furthermore, examples of strategies and current progress in CXCL12-CXCR4 axis-targeted development of therapeutic anticancer inhibitors are discussed.

Tumor-intrinsic IFNα and CXCL10 are critical for immunotherapeutic efficacy by recruiting and activating T lymphocytes in tumor microenvironment.

Tumor immunotherapies targeting PD-(L)1 exhibit anti-tumor efficacy in only 10-30% of patients with various cancers. Literature has demonstrated that a "hot tumor" which contains high T lymphocytes in the tumor microenvironment exhibits a better response to immunotherapies than a "cold tumor." This study aimed to investigate whether tumor-intrinsic IFNα and CXCL10 determine the recruitment and activation of CD8+ T cells to become "hot tumor." In this study, we found that CXCL10 overexpressed in a variety of tumors including lung, colon, and liver tumors with a correlation with PD-L1. High PD-L1 and CXCL10 are associated with better survival rates in tumor patients receiving immunotherapies. IFNs-downstream transcriptional factor IRF-1 and STAT1 were correlated with PD-L1 and CXCL10 expression. We demonstrated that IRF-1 and STAT1 were both bound with the promoters of PD-L1 and CXCL10, sharing the same signaling pathway and determining IFNs-mediated PD-L1 and CXCL10 expression. In addition, IFNα significantly increased activation marker IFNγ in PBMCs, promoting M1 type monocyte differentiation, CD4+ T, and CD8+ T cell activation. Particularly, we found that CD8+ T lymphocytes abundantly expressed CXCR3, a receptor of CXCL10, by flow cytometry, indicating that tumor-intrinsic CXCL10 potentially recruited CD8+ T in tumor microenvironment. To demonstrate the hypothesis, immunotherapy-sensitive CT26 and immunotherapy-resistant LL/2 were used and we found that CT26 cells exhibited higher IFNα, IFNγ, CXCL10, and PD-L1 levels compared to LL/2, leading to higher IFNγ expression in mouse splenocytes. Moreover, we found that CD8+ T cells were recruited by CXCL10 in vitro, whereas SCH546738, an inhibitor of CXCR3, inhibited T cell migration and splenocytes-mediated anti-tumor effect. We then confirmed that CT26-derived tumor was sensitive to αPD-L1 immunotherapy and LL/2-tumor was resistant, whereas αPD-L1 significantly increased T lymphocyte activation marker CD107a in CT26-derived BALB/c mice. In conclusion, this study revealed that CXCL10 expression is correlated with PD-L1 in tumors, sharing the same signaling pathway and associating with better immunotherapeutic efficacy. Further evidence in the syngeneic tumor models demonstrated that immunotherapy-sensitive CT26 intrinsically exhibited higher IFNα and CXCL10 compared to immunotherapy-resistant LL/2 to recruit and activate CD8+ T cells in the tumor microenvironment, exhibiting "hot tumor" characteristic of sensitizing αPD-L1 immunotherapies.

Enhanced photocatalytic regeneration of carboxymethyl cellulose/lignin/ZnO complex hydrogel after methylene blue adsorption.

The biodegradable, nontoxic, and renewable carboxymethyl cellulose (CMC) hydrogel has been developed into a green adsorbent. However, the weak chemical interaction limits its adsorption capability and reusability. This work incorporated lignin with complex structure and ZnO nanoparticles with photocatalytic properties into CMC hydrogel beads to improve the removal of methylene blue (MB) through chemical interaction. Scanning electron microscopic images and Fourier-transform infrared spectra confirmed the compatibility between lignin and ZnO nanoparticles as well as the increment of active sites for dye removal. The MB adsorption on CMC hydrogel beads was more significantly affected by the temperate and initial concentration compared to contact time, pH, and adsorbent dosage. The MB adsorption capacity of CMC hydrogel was improved to 276.79 mg/g after incorporating lignin and ZnO nanoparticles. The adsorption followed the pseudo-second-order kinetic model and Langmuir isotherm model, indicating chemical adsorption. After 6 cycles, the adsorption capacity was reduced by about 15 %. The UV irradiation could recover and improve MB adsorption capacity of CMC hydrogel beads containing ZnO nanoparticles due to the introduction of reactive oxygen species.

The construction of machine learning-based predictive models for high-quality embryo formation in poor ovarian response patients with progestin-primed ovarian stimulation.

OBJECTIVE: To explore the optimal models for predicting the formation of high-quality embryos in Poor Ovarian Response (POR) Patients with Progestin-Primed Ovarian Stimulation (PPOS) using machine learning algorithms. METHODS: A retrospective analysis was conducted on the clinical data of 4,216 POR cycles who underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) at Sichuan Jinxin Xinan Women and Children's Hospital from January 2015 to December 2021. Based on the presence of high-quality cleavage embryos 72 h post-fertilization, the samples were divided into the high-quality cleavage embryo group (N = 1950) and the non-high-quality cleavage embryo group (N = 2266). Additionally, based on whether high-quality blastocysts were observed following full blastocyst culture, the samples were categorized into the high-quality blastocyst group (N = 124) and the non-high-quality blastocyst group (N = 1800). The factors influencing the formation of high-quality embryos were analyzed using logistic regression. The predictive models based on machine learning methods were constructed and evaluated accordingly. RESULTS: Differential analysis revealed that there are statistically significant differences in 14 factors between high-quality and non-high-quality cleavage embryos. Logistic regression analysis identified 14 factors as influential in forming high-quality cleavage embryos. In models excluding three variables (retrieved oocytes, MII oocytes, and 2PN fertilized oocytes), the XGBoost model performed slightly better (AUC = 0.672, 95% CI = 0.636-0.708). Conversely, in models including these three variables, the Random Forest model exhibited the best performance (AUC = 0.788, 95% CI = 0.759-0.818). In the analysis of high-quality blastocysts, significant differences were found in 17 factors. Logistic regression analysis indicated that 13 factors influence the formation of high-quality blastocysts. Including these variables in the predictive model, the XGBoost model showed the highest performance (AUC = 0.813, 95% CI = 0.741-0.884). CONCLUSION: We developed a predictive model for the formation of high-quality embryos using machine learning methods for patients with POR undergoing treatment with the PPOS protocol. This model can help infertility patients better understand the likelihood of forming high-quality embryos following treatment and help clinicians better understand and predict treatment outcomes, thus facilitating more targeted and effective interventions.

Assessment of solar geoengineering impact on precipitation and temperature extremes in the Muda River Basin, Malaysia using CMIP6 SSP and GeoMIP6 G6 simulations.

The concept of solar geoengineering remains a topic of debate, yet it may be an effective way for cooling the Earth's temperature. Nevertheless, the impact of solar geoengineering on regional or local climate patterns is an active area of research. This study aims to evaluate the impact of solar geoengineering on precipitation and temperature extremes of the Muda River Basin (MRB), a very important agricultural basin situated in the northern Peninsular Malaysia. The analysis utilized the multi-model ensemble mean generated by four models that contributed to the Geoengineering Model Intercomparison Project (GeoMIP6). These models were configured to simulate the solar irradiance reduction (G6solar) and stratospheric sulfate aerosols (G6sulfur) strategies as well as the moderate (SSP245) and high emission (SSP585) experiments. Prior to the computation of extreme indices, a linear scaling approach was employed to bias correct the daily precipitation, maximum and minimum temperatures. The findings show that the G6solar and G6sulfur experiments, particularly the latter, could be effective in holding the increases in both annual and monthly mean precipitation totals and temperature extremes close to the increases projected under SSP245. For example, both G6solar and G6sulfur experiments project increases of temperature over the basin of 2 °C at the end of the 21st century as compared to 3.5 °C under SSP585. The G6solar and G6sulfur experiments also demonstrate some reliability in modulating the increases in precipitation extreme indices associated with flooding to match those under SSP245. However, the G6sulfur experiment may exacerbate dry conditions in the basin, as monthly precipitation is projected to decrease during the dry months from January to May and consecutives dry days are expected to increase, particularly during the 2045-2064 and 2065-2084 periods. Increases dry spells could indirectly affect agricultural and freshwater supplies, and pose considerable challenges to farmers.

Evaluation of Collagen Dermal Filler with Lidocaine for the Correction of Nasolabial Folds: A Randomized, Double-Blind, Multicenter Clinical Trial.

Purpose: Porcine-based dermal injectable collagen is effective for nasolabial fold correction. In the present study, a new dermal injectable collagen, incorporating a novel cross-linking technology and premixed with lidocaine, was introduced. The study aimed to determine the efficacy of the new dermal injectable collagen in improving bilateral nasolabial fold wrinkles, and reducing pain during injection. Patients and Methods: This prospective, double-blind, multicenter, parallel-group, randomized trial enrolled participants with moderate-to-severe bilateral nasolabial fold wrinkles from February 2019 to March 2021. Participants were randomly assigned to the test group (new dermal injectable collagen with lidocaine featuring a novel cross-linking technology) or control group (traditionally cross-linked dermal injectable collagen with lidocaine). Participants were monitored for adverse events (AEs), and for pain using the Thermometer Pain Scale (TPS) and a visual analog scale (VAS). Efficacy was measured using the Wrinkle Severity Rating Scale (WSRS) and the Global Aesthetic Improvement Scale (GAIS). Results: On the poor or better sides, the 2 groups exhibited a significant decrease in WSRS scores at 4, 12, 24, and 36 weeks after treatment, compared to baseline WSRS scores (all, p < 0.05). Compared to the control group, the test group had a greater decrease in WSRS score (poor or better sides) at 12, 24, 36, and 52 weeks after treatment (all, p < 0.05). A similar observation was also found in the WSRS response rate and GAIS score of the 2 groups. VAS and TPS scores were not significantly different between the 2 groups (p > 0.05), indicating that pain reduction was similar in the 2 groups. All AEs were anticipated AEs associated with facial aesthetic injections, and most recovered within 0 to 30 days without sequelae. There were no differences in AEs between the 2 groups (all, p > 0.05). Conclusion: The new dermal injectable collagen with lidocaine exhibited better efficacy for correcting nasolabial fold wrinkles compared to the control group. Both relieved pain and produced only transient and tolerable AEs.

Transition Metal Chelation Effect in MOF-253 Materials: Guest Molecule Adsorption Dynamics and Proposed Formic Acid Synthesis Investigated by Atomistic Simulations.

The dynamic characterization of guest molecules in the metal-organic frameworks (MOFs) can always provide the insightful and inspiring information to facilitate the synthetic design of MOF materials from the bottom-up design of perspective. Herein, we present a series of atomistic molecular dynamics simulation for investigating the bipyridine dicarboxylate (bpydc) linker rotation effect on guest molecule adsorption with and without considering the transition metal (TM) chelation in MOF-253 materials. The simulated PXRD patterns of the various linker orientations present the challenge of distinguishing these structural varieties by the conventional crystalline spectroscopic measurements. The observed short inter-TM stable structure may subsequently lead to the formation of a binuclear TM catalytic site, and a proposed formic acid generation mechanism from CO2 and H2 is derived based upon the density functional theory calculations for the application of CO2 reduction.

A novel theory for rapid localization of the transverse-sigmoid sinus junction and "keyhole" in the retrosigmoid keyhole approach: micro-anatomical study, technique nuances, and clinical application.

To determine a rapid and accurate method for locating the keypoint and "keyhole" in the suboccipital retrosigmoid keyhole approach. (1) Twelve adult skull specimens were selected to locate the anatomical landmarks on the external surface of the skull.The line between the infraorbital margin and superior margin of the external acoustic meatus was named the baseline. A coordinate system was established using the baseline and its perpendicular line through the top point of diagastric groove.The perpendicular distance (x), and the horizontal distance (y) between the central point of the "keyhole" and the top point of the digastric groove in that coordinate system were measured. The method was applied to fresh cadaveric specimens and 53 clinical cases to evaluate its application value. (1) x and y were 14.20 ± 2.63 mm and 6.54 ± 1.83 mm, respectively (left) and 14.95 ± 2.53 mm and 6.65 ± 1.61 mm, respectively (right). There was no significant difference between the left and right sides of the skull (P > 0.05). (2) The operative area was satisfactorily exposed in the fresh cadaveric specimens, and no venous sinus injury was observed. (3) In clinical practice, drilling did not cause injury to venous sinuses, the mean diameter of the bone windows was 2.0-2.5 cm, the mean craniotomy time was 26.01 ± 3.46 min, and the transverse and sigmoid sinuses of 47 patients were well-exposed. We propose a "one point, two lines, and two distances" for "keyhole" localization theory, that is we use the baseline between the infraorbital margin and superior margin of the external acoustic meatus and the perpendicular line to the baseline through the top point of the digastric groove to establish a coordinate system. And the drilling point was 14.0 mm above and 6.5 mm behind the top point of the digastric groove in the coordinate system.

Outcome of patients with complete cleft lip and alveolus: 20-year follow-up.

BACKGROUND: Patients with cleft have functional and aesthetic impairment, and typically require several interventions as they grow. Long-term evaluation following a treatment protocol is essential, but such reports on patients with complete cleft lip and alveolus (CLA) are sparse in the literature. METHODS: A retrospective review was conducted to all patients with complete CLA born between January 1995 and August 2002 and treated at our center. Patients who received continuous multidisciplinary team care until 20 years of age were included, and patients with cleft palate and syndromic abnormalities were excluded. Facial bone growth was evaluated using cephalometric analysis. RESULTS: Eighty-seven and 11 patients with unilateral and bilateral CLA (UCLA and BCLA) were included respectively. All patients received one-stage cheiloplasty with primary rhinoplasty. Revisional lip/nose surgery was performed in 21.8 and 27.3% during growing age, and in 51.7 and 72.7% after skeletal maturity. Orthognathic surgery was performed in 20.7 and 27.3%. Compared with UCLA patients, BCLA had larger number of operations (3.0 versus 3.7, p = 0.03) and higher chance of receiving alveolar bone grafting twice (1.1% versus 36.4%, p < 0.01). Patients with complete CLA had less hypoplastic maxilla, and received smaller number of operations than complete cleft lip and palate. CONCLUSION: Complete CLA is a less severe form of cleft, but the patients still require multiple interventions. This review revealed certain suboptimal results, and modifications have been made in the treatment protocol. Longitudinal follow-up and periodic assessment help to establish an ideal therapeutic strategy and improve overall cleft care.

Triple click chemistry for crosslinking, stiffening, and annealing of gelatin-based microgels.

Microgels are spherical hydrogels with physicochemical properties ideal for many biomedical applications. For example, microgels can be used as individual carriers for suspension cell culture or jammed/annealed into granular hydrogels with micron-scale pores highly permissive to molecular transport and cell proliferation/migration. Conventionally, laborious optimization processes are often needed to create microgels with different moduli, sizes, and compositions. This work presents a new microgel and granular hydrogel preparation workflow using gelatin-norbornene-carbohydrazide (GelNB-CH). As a gelatin-derived macromer, GelNB-CH presents cell adhesive and degradable motifs while being amenable to three orthogonal click chemistries, namely the thiol-norbornene photo-click reaction, hydrazone bonding, and the inverse electron demand Diels-Alder (iEDDA) click reaction. The thiol-norbornene photo-click reaction (with thiol-bearing crosslinkers) and hydrazone bonding (with aldehyde-bearing crosslinkers) were used to crosslink the microgels and to realize on-demand microgel stiffening, respectively. The tetrazine-norbornene iEDDA click reaction (with tetrazine-bearing crosslinkers) was used to anneal microgels into granular hydrogels. In addition to materials development, we demonstrated the value of the triple-click chemistry granular hydrogels via culturing human mesenchymal stem cells and pancreatic cancer cells.

Punicalagin Restricts Growth, Promotes Apoptosis, and Reduces Invasion in Human Gastric Cancer Cells.

This research investigated the anticancer properties of punicalagin, a prominent bioactive polyphenol extracted from Punica granatum L, in human gastric cancer cell lines. Normal and gastric cancer cells were exposed to different doses of punicalagin for various durations. Punicalagin exhibited cytotoxic effects on gastric cancer cells in a dose- and time-dependent fashion, while sparing normal gastric epithelial cells. It is noteworthy that among the 3 gastric cancer cells, HGC-27 cells were more resistant to punicalagin than 23,132/87 and AGS cells. Furthermore, punicalagin triggered apoptosis in gastric cancer cells, evidenced by a rise in both early and late apoptotic cell percentages. Western blot analysis further revealed that punicalagin elevated the levels of activated caspase-3. Conversely, punicalagin curtailed cell invasion and reduced the expression of MMP-2, MMP-9, Snail, and Slug. From a mechanistic standpoint, Western blotting indicated that punicalagin might inhibit the Erk and NF-κB pathways, leading to apoptosis induction and the inhibition of cell invasion in gastric cancer cells. These results indicate that punicalagin promotes apoptosis and inhibits cell invasion in gastric cancer cells by activating caspase-3 and suppressing MMP-2, MMP-9, Snail, and Slug through the inhibition of the Erk and NF-κB pathways.

Combination of plant metabolites hinders starch digestion and glucose absorption while facilitating insulin sensitivity to diabetes.

Introduction: Diabetes mellitus (DM) is a common endocrine disease resulting from interactions between genetic and environmental factors. Type II DM (T2DM) accounts for approximately 90% of all DM cases. Current medicines used in the treatment of DM have some adverse or undesirable effects on patients, necessitating the use of alternative medications. Methods: To overcome the low bioavailability of plant metabolites, all entities were first screened through pharmacokinetic, network pharmacology, and molecular docking predictions. Experiments were further conducted on a combination of antidiabetic phytoactive molecules (rosmarinic acid, RA; luteolin, Lut; resveratrol, RS), along with in vitro evaluation (α-amylase inhibition assay) and diabetic mice tests (oral glucose tolerance test, OGTT; oral starch tolerance test, OSTT) for maximal responses to validate starch digestion and glucose absorption while facilitating insulin sensitivity. Results: The results revealed that the combination of metabolites achieved all required criteria, including ADMET, drug likeness, and Lipinski rule. To determine the mechanisms underlying diabetic hyperglycemia and T2DM treatments, network pharmacology was used for regulatory network, PPI network, GO, and KEGG enrichment analyses. Furthermore, the combined metabolites showed adequate in silico predictions (α-amylase, α-glucosidase, and pancreatic lipase for improving starch digestion; SGLT-2, AMPK, glucokinase, aldose reductase, acetylcholinesterase, and acetylcholine M2 receptor for mediating glucose absorption; GLP-1R, DPP-IV, and PPAR-γ for regulating insulin sensitivity), in vitro α-amylase inhibition, and in vivo efficacy (OSTT versus acarbose; OGTT versus metformin and insulin) as nutraceuticals against T2DM. Discussion: The results demonstrate that the combination of RA, Lut, and RS could be exploited for multitarget therapy as prospective antihyperglycemic phytopharmaceuticals that hinder starch digestion and glucose absorption while facilitating insulin sensitivity.

A theoretical study of the electron paramagnetic resonance spectra and local environment in copper(II) complexes with different imidazole and chlorido ligands.

Copper(II) chloride anionic coordination complexes with different imidazole-derived ligands due to the potential cytotoxic activity play the important role in protein. By investigating the experimental electron paramagnetic resonance (EPR) and ultraviolet-visible (UV-vis) spectra of [CuCl(C6H10N2)4]Cl, [CuCl(C6H10N2)4]Cl, [CuCl2(C4H6N2)4], and [Cu2Cl2(C5H8N2)6]Cl2·2H2O, the local structure of the corresponding Cu2+ centers and the role of different ligands are obtained. Based on the well-agreed EPR parameters and the d-d transitions (10Dq), the four Cu2+ centers show tetragonal and orthorhombic distortion, corresponding to the different anisotropies of EPR signals. In addition, the general rules of governing the impact of methanol in imidazolylalkyl derivatives are also discussed, especially the influence on the local environment (symmetry, distortion, covalency, and crystal field) of above four copper(II) chloride anionic coordination complexes. Therefore, the obtained results in this study will be beneficial to provide a theoretical basis for the experimental design of desired copper-containing imidazolyl alkyl derivatives.

Disc Height and Angle Changes on Radiographs and Magnetic Resonance Imaging after Anterior or Posterior Percutaneous Endoscopic Cervical Discectomy.

Objectives: Cervical disc herniation (CDH) leads to pain, numbness, and potential disability. Percutaneous endoscopic cervical discectomy (PECD) offers an anterior or posterior approach. This study aims to compare postoperative disc height and angle changes one year after PECD, considering both approaches. Methods: We retrospectively reviewed the data from patients with CDH who underwent PECD from October 2017 to July 2022. Cervical disc height was measured using the preoperative and one-year postoperative magnetic resonance imaging (MRI) examinations. Lordotic angle (LA), global alignment angle (GAA), segmental alignment angle (SAA), and slippage distance (SD) at the surgical level were measured on radiographs in the neutral, flexion, and extension positions. Results: Thirty-eight patients who underwent posterior PECD (PPECD) and five patients who underwent anterior PECD (APECD) were included in the evaluation. The mean age of the patients was 47.4 years (range: 29-69 years). There was a significant difference in the preoperative and one-year postoperative GAA and SAA in extension in the PPECD group (p = 0.003 and 0.031, respectively). The mean decreased disc height one-year postoperative was 1.30 mm in the APECD group and 0.3 mm in the PPECD group by MRI. A significant disc height decrease was observed in the APECD group (p < 0.001). Conclusions: Treating CDH with PPECD or APECD is feasible, as it can relieve symptoms and reduce disability. Stability remained unaffected during the first year after surgery, even though there was an increase in angulation during extension. Despite a significant decrease in disc space following APECD, patients reported significant symptom improvement and no new symptoms.

Synthesis and Inclusion Properties of a ß-Cyclodextrin Heptaphosphoramidate.

In this study, we report a novel per-6-substituted ß-cyclodextrin (4) featuring seven phosphoramidate moieties as an innovative host for inclusion. This structurally well-defined host has remarkable water solubility and was isolated in pure form. Analytical techniques such as NMR and ITC were used to probe the molecular interactions with different drug molecules. Our investigations revealed that host 4 can form 2:1 inclusion complexes with various drugs. Further studies showed that the inclusions of drugs by ß-CD host (4) are mostly enthalpy driven, highlighting the potential roles played by the phosphoramidate functionalities of the host. Comparatively, a per-O2, O3-acetylated analog (6) of compound 4 was also obtained, which also shows unusual water solubility but diminished inclusion capability.