Efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome.

The objective of this study was to evaluate the efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome (CPPS). A total of 79 female patients diagnosed with CPPS from January 2021 to December 2022 were prospectively analyzed. Every patient received 3 weeks of treatment which included myofascial release therapy combined with electrical and magnetic stimulation. The visual analog score (VAS) of pelvic floor muscle (PFM) trigger points (TrPs) and the changes in pelvic floor surface electromyography before and after treatment were compared. Multiple linear regression was used to analyze the influencing factors of each outcome index. There were significant differences in VASs of muscle TrPs before and after treatment (P < 0.05). For the surface electromyography of PFMs, the differences in pre-baseline rest, post-baseline rest, isometric contractions for muscle endurance evaluation, and coefficient of variation were statistically significant (P < 0.05). Linear regression analysis showed that disease course (X 1), dyspareunia (X 5), and urinary incontinence (X 6) were influencing factors for the decline of pre-baseline rest (r5 = 1.067, R 2 = 0.089), post-baseline rest (r1 = 0.055, r5 = 0.99, R 2 = 0.119), VASs of ischial spine (r5 = 0.916, R 2 = 0.102), obturator internus (r5 = 0.796, r6 = -0.703, R 2 = 0.245), and pubococcygeus (r5 = 0.885, R 2 = 0.149) after treatment in the CPPS group. This study confirmed that individualized myofascial release therapy combined with electrical and magnetic stimulation has significant efficacy for patients with CPPS. At the same time, it is more effective for CPPS patients with longer course of disease, dyspareunia, and without urinary incontinence.

Visible-light-induced N-alkylation of anilines with 4-hydroxybutan-2-one.

The synthesis of amines through N-alkylation is particularly attractive. Herein, a strategy for visible-light-induced N-alkylation of anilines with 4-hydroxybutan-2-one was developed in the presence of NH4Br, which avoid the use of metals, bases and ligands. In addition, gram-scale experiments proved that the system has the potential to be scaled.

Prevalence and genetic basis of Mycobacterium tuberculosis resistance to pretomanid in China.

BACKGROUND: Pretomanid is a key component of new regimens for the treatment of drug-resistant tuberculosis (TB) which are being rolled out globally. However, there is limited information on the prevalence of pre-existing resistance to the drug. METHODS: To investigate pretomanid resistance rates in China and its underlying genetic basis, as well as to generate additional minimum inhibitory concentration (MIC) data for epidemiological cutoff (ECOFF)/breakpoint setting, we performed MIC determinations in the Mycobacterial Growth Indicator Tube™ (MGIT) system, followed by WGS analysis, on 475 Mycobacterium tuberculosis (MTB) isolated from Chinese TB patients between 2013 and 2020. RESULTS: We observed a pretomanid MIC distribution with a 99% ECOFF equal to 0.5 mg/L. Of the 15 isolates with MIC values > 0.5 mg/L, one (MIC = 1 mg/L) was identified as MTB lineage 1 (L1), a genotype previously reported to be intrinsically less susceptible to pretomanid, two were borderline resistant (MIC = 2-4 mg/L) and the remaining 12 isolates were highly resistant (MIC ≥ 16 mg/L) to the drug. Five resistant isolates did not harbor mutations in the known pretomanid resistant genes. CONCLUSIONS: Our results further support a breakpoint of 0.5 mg/L for a non-L1 MTB population, which is characteristic of China. Further, our data point to an unexpected high (14/475, 3%) pre-existing pretomanid resistance rate in the country, as well as to the existence of yet-to-be-discovered pretomanid resistance genes.

Effect of dietary supplementation with recombinant human lysozyme on growth performance, antioxidative characteristics and intestinal health in broiler chickens.

Lysozyme is often used as a feed additive to act as an antibacterial protein that boosts the immune system of livestock and poultry while protecting against pathogens. To investigate effects of recombinant human lysozyme (rhLYZ) rom Pichia pastoris and chlortetracycline on broiler chicken's production performance, antioxidant characteristics, and intestinal microbiota, a total of 200, one-day-old male Arbor Acres broiler chickens (46.53±0.42 g) were selected for a 42-day experiment. Dietary treatments included: a basal diet of corn-soybean meal supplemented with either 0 mg/kg (CON), 50 mg/kg aureomycin (ANT), 20 mg/kg rhLYZ (LOW), 60 mg/kg rhLYZ (MEDIUM), or 180 mg/kg rhLYZ (HIGH). Compared with CON, MEDIUM diet increased (p < 0.05) average daily gain (ADG)(= 67.40g) of broilers from day 22 to 42. In the early (= 1.29) and overall phases (= 1.69), MEDIUM led to a reduction (P<0.05) in feed conversion ratio (FCR) of broiler chickens. Furthermore, in comparison to the CON and ANT, MEDIUM exhibited reduced (P<0.05) levels of INF-γ and TNF-α in the serum. In the cecum, the abundance of Monoglobus and Family_XIII_AD3011_group was lower (P < 0.05) in the MEDIUM treatment compared to CON. Overall, supplementation of 60 mg/kg of rhLYZ improved growth performance, nutrient utilization efficiency, and serum immune function, while also influencing composition of intestinal microbiota. This suggests lysozyme's potential to replace antibiotic additives in feed.

Aspirin use and changes in circulating tumor DNA levels in patients with metastatic colorectal cancer.

The study aimed to investigate the effects of aspirin on patients with metastatic colorectal cancer, focusing on circulating tumor DNA levels and bone tissue. Two groups (A and B) of ten patients with osteoporosis were selected for the study. Bone tissue samples were obtained from the patients and cultured under sterile conditions. The aspirin group showed a significant decrease in circulating tumor DNA levels and an increase in bone tissue density compared to the control group. Additionally, osteoblast apoptosis was reduced, while proliferation was enhanced in the aspirin group. The protein pAkt related to the PI3K/Akt signaling pathway was upregulated in the aspirin group. These results indicate that aspirin can effectively lower circulating tumor DNA levels, promote bone tissue proliferation, inhibit apoptosis, and activate the PI3K/Akt signaling pathway, thereby influencing bone cell function. These findings provide a basis for aspirin's potential application in treating metastatic colorectal cancer and encourage further research on its mechanism and clinical use.

A new genetic diagnosis strategy for paroxysmal kinesigenic dyskinesia: Targeted high-throughput detection of PRRT2 gene c.649 locus.

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is the most prevalent kind type of paroxysmal Dyskinesia, characterized by recurrent and transient episodes of involuntary movements. Most PKD cases were attributed to the proline-rich transmembrane protein 2 (PRRT2) gene, in which the c.649 region is a hotspot for known mutations. Even though some patients with PKD have been genetically diagnosed using whole-exome sequencing (WES) and Sanger sequencing, there are still cases of missed diagnoses due to the limitations of sequencing technology and analytic methods on throughput. METHODS: Patients meeting the diagnosis criteria of PKD with negative results of PRRT2-Sanger sequencing and WES were included in this study. Mutation screening and targeted high-throughput sequencing were performed to analyze and verify the sequencing results of the potential mutations. RESULTS: Six patients with PKD with high mutation ratios of c.649dupC were screened using our targeted high-throughput sequencing from 26 PKD patients with negative results of PRRT2-Sanger sequencing and WES (frequency = 23.1%), which compensated for the comparatively shallow sequencing depth and statistical flaws in this region. Compared with the local normal population and other patients with PKD, the mutation ratios of c.649dupC of these six patients with PKD were much higher and also had truncated protein structures and differentially altered mRNA expression. CONCLUSION: Based on the above studies, we emphasize the routine targeted high-throughput sequencing of the c.649 site in the PRRT2 gene in so-called genetic-testing-negative patients with PKD, and manually calculate the deletion and duplication mutations depth and ratios to lower the rate of clinical misdiagnosis.

Relationship Between Square Dancing and Meaning in Life Among Older Adults: Examining an Age-Based Moderation Model.

PURPOSE: Square dancing may help older adults experience meaning in life (MIL). However, it remains unclear how square dancing facilitates MIL. To address this question, we examined whether participation frequency, transcendent experiences, and social support correlated positively with MIL, and whether age moderated the correlation between transcendent experiences and MIL. METHOD: We studied 268 older adults using in-person surveys to collect data on age, participation frequency, transcendent experiences, social support, and MIL. We analyzed data using hierarchical regression. RESULTS: High frequency of participation and high levels of transcendent experiences and social support simultaneously predicted high levels of MIL, and age decreased the positive relationship between transcendent experiences and MIL. CONCLUSION: Based on the hierarchical regression results, we recommend strategies to increase older adults' MIL by providing square dancing opportunities; working with them to improve square dancing skills that facilitate transcendent experiences; and guiding them in seeking sources of social support. [Research in Gerontological Nursing, 17(3), 141-147.].

Magnetic-stirring-enhanced mechanical amorphous dispersion extraction for the hydrophobic phytochemical constituents using an aqueous solution from a medicinal plant.

A method involving chitosan-assisted magnetic-stirring-enhanced mechanical amorphous dispersion extraction was developed and utilized to extract hydrophobic anthraquinones from Rhei Radix et Rhizoma prior to ultrahigh performance liquid chromatography analysis. Incorporating natural chitosan as a dispersant facilitated the extraction of hydrophobic anthraquinones using purified water, considerably enhancing the eco-friendliness of the extraction methodology. To optimize extraction efficiency, an extensive evaluation of the crucial parameters influencing rhubarb yield was conducted. Furthermore, a response surface methodology was applied to optimize the extraction conditions. Under these optimized conditions, the method exhibited linearity ranges of 0.1-100 µg/mL, with correlation coefficients between 0.9990 and 0.9998. The method's intraday (n = 6) and interday (n = 6) precision levels were maintained at ≤3.58%, which was considered to be within acceptable limits. The computed detection and quantification limits were 16.54-24.60 and 54.91-82.04 ng/mL, respectively. Consequently, this optimized method was effectively employed to extract five specific compounds (aloe-emodin, emodin, rhein, chrysophanol, and physcion) from Rhei Radix et Rhizoma, achieving recoveries ranging from 86.43% to 102.75%.

Effects of polysaccharides on colonic targeting and colonic fermentation of ovalbumin-ferulic acid based emulsion.

Rutin is a polyphenol with beneficial pharmacological properties. However, its bioavailability is often compromised due to low solubility and poor stability. Encapsulation technologies, such as emulsion systems, have been proven to be promising delivery vehicles for enhancing the bioavailability of bioactive compounds. Thus, this study was proposed and designed to investigate the colonic targeting and colonic fermentation characteristics of rutin-loaded ovalbumin-ferulic acid-polysaccharide (OVA-FA-PS) complex emulsions. The results indicate that OVA-FA-PS emulsion effectively inhibits the degradation of rutin active substances and facilitates its transport of rutin to the colon. The analysis revealed that the OVA-FA-κ-carrageenan emulsion loaded with rutin exhibited superior elasticity and colon targeting properties compared to the OVA-FA-hyaluronic acid or OVA-FA-sodium alginate emulsions loaded with rutin in the composite emulsion. Additionally, it was observed that the rutin loaded within the OVA-FA-κ-carrageenan emulsion underwent degradation and was converted to 4-hydroxybenzoic acid during colonic fermentation.

Identifying interactive effects of spatial drivers in soil heavy metal pollutants using interpretable machine learning models.

The accurate identification of spatial drivers is crucial for effectively managing soil heavy metals (SHM). However, understanding the complex and diverse spatial drivers of SHM and their interactive effects remains a significant challenge. In this study, we present a comprehensive analysis framework that integrates Geodetector, CatBoost, and SHapley Additive exPlanations (SHAP) techniques to identify and elucidate the interactive effects of spatial drivers in SHM within the Pearl River Delta (PRD) region of China. Our investigation incorporated fourteen environmental factors and focused on the pollution levels of three prominent heavy metals: Hg, Cd, and Zn. These findings provide several key insights: (1) The distribution of SHM is influenced by the combined effects of various individual factors and interactions within the source-flow-sink process. (2) Compared with the spatial interpretation of individual factors, the interaction between Hg and Cd exhibited enhanced spatial explanatory power. Similarly, interactions involving Zn mainly demonstrated increased spatial explanatory power, but there was one exception in which a weakening was observed. (3) Spatial heterogeneity plays a crucial role in determining the contributions of environmental factors to soil heavy metal concentrations. Although individual factors generally promote metal accumulation, their effects fluctuate when interactions are considered. (4) The SHAP interpretable method effectively addresses the limitations associated with machine-learning models by providing understandable insights into heavy metal pollution. This enables a comparison of the importance of environmental factors and elucidates their directional impacts, thereby aiding in the understanding of interaction mechanisms. The methods and findings presented in this study offer valuable insights into the spatial heterogeneity of heavy metal pollution in soil. By focusing on the effects of interactive factors, we aimed to develop more accurate strategies for managing SHM pollution.

Recent advances in cryotolerance biomarkers for semen preservation in frozen form-A systematic review.

Spermatozoa cryopreservation has been practiced for decades and is a very useful technique for long-term preservation of sperm fertility. The capability for semen cryopreservation varies across species, seasons, latitudes, and even for different ejaculates from the same animal. This article summarizes research results on sperm cryotolerance biomarkers in several species, focusing on three areas: spermatozoa cryotolerance biomarkers, seminal plasma proteins cryotolerance biomarkers, and other cryotolerance biomarkers. We discovered that sperm cryoresistance biomarkers are primarily related to sperm plasma membrane stability, the presence of antioxidant substances in sperm or seminal plasma, sperm cell energy metabolism, water and small molecule transport channels in the sperm plasma membrane, and antistress substances in sperm or seminal plasma. The research conducted using diverse livestock models can be employed to enhance the basic and applied reproduction of other mammals through the study of sperm cryotolerance biomarkers, as well as the substantial similarities between livestock and other organisms, including endangered species.

Identifying influence factors and thresholds of the next day's pollen concentration in different seasons using interpretable machine learning.

The prevalence of pollen allergies is a pressing global issue, with projections suggesting that half of the world's population will be affected by 2050 according to the estimation of the World Health Organization (WHO). Accurately forecasting pollen allergy risks requires identifying key factors and their thresholds for aerosol pollen. To address this, we developed a technical framework combining advanced machine learning and SHapley Additive exPlanations (SHAP) technology, focusing on Beijing. By analyzing meteorological data and vegetation phenology, we identified the factors influencing next-day's pollen concentration (NDP) in Beijing and their thresholds. Our results highlight vegetation phenology data from Synthetic Aperture Radar (SAR), temperature, wind speed, and atmospheric pressure as crucial factors in spring. In contrast, the Normalized Difference Vegetation Index (NDVI), air temperature, and wind speed are significant in autumn. Leveraging SHAP technology, we established season-specific thresholds for these factors. Our study not only confirms previous research but also unveils seasonal variations in the relationship between radar-derived vegetation phenology data and NDP. Additionally, we observe seasonal fluctuations in the influence patterns and threshold values of daily air temperatures on NDP. These insights are pivotal for improving pollen concentration prediction accuracy and managing allergic risks effectively.

Targeting HIF-1α with Specific DNA Yokes for Effective Anticancer Therapy.

Hypoxia, a ubiquitous hallmark in cancer, underscores the significance of targeting HIF-1α, the principal transcriptional factor of hypoxic responses, for effective cancer therapy. Herein, DNA yokes, a novel class of DNA nanomaterials harboring specific HIF-1α binding sequences (hypoxia response elements, HREs), are introduced as nanopharmaceuticals for cancer treatment. Comprising a basal tetrahedral DNA nanostructure and four HRE-bearing overhanging chains, DNA yokes exhibit exceptional stability and prolonged intracellular retention. The investigation reveals their capacity to bind HIF-1α, thereby disrupting its interaction with the downstream genomic DNAs and impeding transcriptional activity. Moreover, DNA yokes facilitate HIF-1α degradation via the ubiquitination pathway, thereby sequestering it from downstream targets and ultimately promoting its degradation. In addition, DNA yokes attenuate cancer cell proliferation, migration, and invasion under hypoxic conditions, while also displaying preferential accumulation within tumors, thereby inhibiting tumor growth and metastasis in vivo. This study pioneers a novel approach to cancer therapy through the development of DNA-based drugs characterized by high stability and low toxicity to normal cells, positioning DNA yokes as promising candidates for cancer treatment.

Population pharmacokinetics of imetelstat, a first-in-class oligonucleotide telomerase inhibitor.

Imetelstat is a novel, first-in-class, oligonucleotide telomerase inhibitor in development for the treatment of hematologic malignancies including lower-risk myelodysplastic syndromes and myelofibrosis. A nonlinear mixed-effects model was developed to characterize the population pharmacokinetics of imetelstat and identify and quantify covariates that contribute to its pharmacokinetic variability. The model was developed using plasma concentrations from 7 clinical studies including 424 patients with solid tumors or hematologic malignancies who received single-agent imetelstat via intravenous infusion at various dose levels (0.4-11.7 mg/kg) and schedules (every week to every 4 weeks). Covariate analysis included factors related to demographics, disease, laboratory results, renal and hepatic function, and antidrug antibodies. Imetelstat was described by a two-compartment, nonlinear disposition model with saturable binding/distribution and dose- and time-dependent elimination from the central compartment. Theory-based allometric scaling for body weight was included in disposition parameters. The final covariates included sex, time, malignancy, and dose on clearance; malignancy and sex on volume of the central compartment; and malignancy and spleen volume on concentration of target. Clearance in females was modestly lower, resulting in nonclinically relevant increases in predicted exposure relative to males. No effects on imetelstat pharmacokinetics were identified for mild-to-moderate hepatic or renal impairment, age, race, and antidrug antibody status. All model parameters were estimated with adequate precision (relative standard error < 29%). Visual predictive checks confirmed the capacity of the model to describe the data. The analysis supports the imetelstat body-weight-based dosing approach and lack of need for dose individualizations for imetelstat-treated patients.

Boron Nitride/Carbon Fiber High-Oriented Thermal Conductivity Material with Leaves-Branches Structure.

In the realm of thermal interface materials (TIMs), high thermal conductivity and low density are key for effective thermal management and are particularly vital due to the growing compactness and lightweight nature of electronic devices. Efficient directional arrangement is a key control strategy to significantly improve thermal conductivity and comprehensive properties of thermal interface materials. In the present work, drawing inspiration from natural leaf and branch structures, a simple-to-implement approach for fabricating oriented thermal conductivity composites is introduced. Utilizing carbon fibers (CFs), known for their ultra-high thermal conductivity, as branches, this design ensures robust thermal conduction channels. Concurrently, boron nitride (BN) platelets, characterized by their substantial in-plane thermal conductivity, act as leaves. These components not only support the branches but also serve as junctions in the thermal conduction network. Remarkably, the composite achieves a thermal conductivity of 11.08 W/(m·K) with just an 11.1 wt% CF content and a 1.86 g/cm3 density. This study expands the methodologies for achieving highly oriented configurations of fibrous and flake materials, which provides a new design idea for preparing high-thermal conductivity and low-density thermal interface materials.

Double cross-linked 3D layered PBI proton exchange membranes for stable fuel cell performance above 200 °C.

Phosphoric acid doped proton exchange membranes often experience performance degradation above 200 °C due to membrane creeping and phosphoric acid evaporation, migration, dehydration, and condensation. To address these issues, here we present gel-state polybenzimidazole membranes with double cross-linked three-dimensional layered structures via a polyphosphoric acid sol-gel process, enabling stable operation above 200 °C. These membranes, featuring proton-conducting cross-linking phosphate bridges and branched polybenzimidazole networks, effectively anchor and retain phosphoric acid molecules, prevent 96% of its dehydration and condensation, improve creep resistance, and maintain excellent proton conductivity stability. The resulting membrane, with superior through-plane proton conductivity of 0.348 S cm-1, delivers outstanding peak power densities ranging from 1.20-1.48 W cm-2 in fuel cells operated at 200-240 °C and a low voltage decay rate of only 0.27 mV h-1 over a 250-hour period at 220 °C, opening up possibilities for their direct integration with methanol steam reforming systems.

Free and bound phenolic profiles of Radix Puerariae Thomsonii from different growing regions and their bioactivities.

The free and bound phenolic profiles and their bioactivities of radix puerariae thomsonii (RPT) cultivars from 7 growing regions in China were investigated. Total phenolic and flavonoid contents were from 148.71 to 435.32 mg gallic acid equivalents /100 g dry weight and 561.93 to 826.11 mg catechin equivalents /100 g dry weight, respectively, with 20.64-38.28% and 32.77-47.29% contribution from bound fractions. Sixteen phenolic compounds were detected in RPTs. Bound fractions contributed 28.15-70.84% to the total antioxidant activities. The cultivars from Qiannan and Guangzhou showed much higher regulatory effects on carbohydrate hydrolyzing enzymes and alcohol metabolizing enzymes than the other cultivars. The bound fractions exhibited equivalent EC50 values for alcohol metabolizing enzymes and IC50 values for carbohydrate hydrolyzing enzymes to the free fractions in RPT cultivars. Therefore, bound phenolics significantly contributed to the potential health benefits of RPT. The results provided information for the utilization of RPT for health promoting purpose.

Gradient Alloy Shell Enabling Colloidal Quantum Wells Light-Emitting Diodes with Efficiency Exceeding 22.

Colloidal quantum well (CQW) based light emitting diodes (LEDs) possess extra-high theoretical efficiency, but their performance still lags far behind conventional LEDs due to severe exciton quenching and unbalanced charge injection. Herein, we devised a gradient composition CdxZn1-xS shell to address these issues. The epitaxial shell with gradient composition was achieved through controlling competition between Cd2+ and Zn2+ cations to preferentially bind to the anions S2-. Thus, exciton quenching was suppressed greatly by passivating defects and reducing nonradiative recombination, thereby achieving near-unity photoluminescence quantum yield (PLQY). The gradient energy level of the shell reduced the hole injection barriers and increased the hole injection efficiency to balance the charge injection of LEDs. As a result, the LEDs achieved a high external quantum efficiency (EQE) of 22.83%, luminance of 111,319 cd/m2 and a long operational lifetime (T95@100 cd/m2) over 6,500 h, demonstrating the state-of-the-art performance for the CQW based LEDs.

Northeast Pacific warm blobs sustained via extratropical atmospheric teleconnections.

Large-scale marine heatwaves in the Northeast Pacific (NEP), identified here and previously as 'warm blobs', have devastating impacts on regional ecosystems. An anomalous atmospheric ridge over the NEP is known to be crucial for maintaining these warm blobs, also causing abnormally cold temperatures over North America during the cold season. Previous studies linked this ridge to teleconnections from tropical sea surface temperature anomalies. However, it was unclear whether teleconnections from the extratropics could also contribute to the ridge. Here we show that planetary wave trains, triggered by increased rainfall and latent heat release over the Mediterranean Sea accompanied by decreased rainfall over the North Atlantic, can transport wave energy to the NEP, guided by the westerly jet, and induce a quasi-barotropic ridge there. Our findings provide insights into extratropical teleconnections sustaining the NEP ridge, offering a source of potential predictability for the warm blobs and temperature fluctuations over North America.