The degradation of α--synuclein is limited by dynein to drive the AALP pathway through HDAC6 upon paraquat exposure.

Lewy body disease (LBD), one of the most common neurodegenerative diseases (NDDs), is characterized by excessive accumulation of α-synuclein (α-syn) in neurons. In recent years, environmental factors such as exposure to herbicides and pesticides have been attributed to the development of this condition. While majority of the studies on neurotoxic effects of paraquat (PQ) have focused on α-syn-mediated neuronal damage in the early stages of α-syn accumulation in neurons, efforts to explore the key target for α-syn degradation are limited. Recent research has suggested that histone deacetylase 6 (HDAC6) might possibly regulate amyloid clearance, and that the metabolism of compounds in neurons is also directly affected by axonal transport in neurons. Dynein predominantly mediates reverse transportation of metabolites and uptake of signal molecules and other compounds at the end of axons, which is conducive to the reuse of cell components. However, the role of interaction of dynein with HDAC6 in metabolites transport is still unclear. Therefore, this study aimed to investigate the role of HDAC6 in α-syn accumulation/clearance in neurons and the associated possible influencing factors. The results revealed that HDAC6 could transport ubiquitinated α-syn, bind to dynein, form an aggresome, and relocate to the center of the microtubule tissue, ultimately reducing abnormal accumulation of α-syn. However, PQ treatment resulted in HDAC6 upregulation, causing abnormal aggregation of α-syn. Taken together, these findings indicated that PQ exposure caused abnormal accumulation of α-syn and decreased effective degradation of α-syn by HDAC6-mediated aggresome-autophagy-lysosome pathway.

Dual-Regulation of Supramolecular Chirality in Achiral Side-Chain Azobenzene Liquid-Crystalline Polymers.

Azobenzene (Azo) liquid-crystalline polymers are intriguing due to their unique photo-induced isomerization and supramolecular chirality. However, clarification on multicomponent chiral induction towards Azo polymers remains ambiguous and challenging. Herein, chiral solvents and amines were employed to control the chiroptical activity of achiral Azo polymers. Methyl L-/D-lactate was added as the poor solvent and chiral inducer to achieve the first chiral induction in Azo aggregates. Chiral amines were utilized for the second chiral induction based on the acid-base interactions between the carboxyl groups of polymers and amines. The chiral enhancement and inversion of Azo units could be observed through the synergistic or antagonistic effect between solvents and amines. The impacts of solvent, chemical structures, feed ratio, enantiomeric excess, and temperature on supramolecular chirality were systematically studied. Furthermore, this system displayed the chiroptical switching property and chiral recovery under reversible irradiation.

Nonlinearly coupled electro-osmotic flow in variable charge soils.

Electro-osmosis has been valued as a promising technology to enhance the dewatering of waste sludge, stabilization and environmental remediation of soils with low permeability. However, the coefficient of electro-osmotic permeability (keo) is commonly taken as constant value which is particularly not the case in variable charge soil. As a result, the nonlinearity of the electro-osmotic flow (EOF) and the direction reverse could not be interpreted. Herein, the electro-chemical parameters were monitored in electro-osmotic experiment with natural variable charge soil. It was observed that the evolutions showed significant nonlinear behavior and were correlated. The comprehensive Zeta potential model proposed by the authors was applied to simulate the nonlinear keo induced by the variable pH and electrolyte concentration. The agreement between tested and simulated flow rate variation and excess pore water pressure distribution demonstrated the reliability of the theory. The error rate of the simulations through coupling nonlinear keo and voltage gradient Ex was reduced to 29.4% from 381.9% of calculations with constant parameters. The direction reverse of EOF was innovatively interpreted. Hence, the numerical model would act as a useful tool to connect these electro-chemical parameters and provide guidance to evaluate contributions of commonly used pH conditioning measurements.

Precise Construction of Chiral Plasmonic Nanoparticles for Enantioselective Discrimination.

Chiral plasmonic nanostructures exhibit potential in the advanced manufacturing industry, due to their fascinating characteristics. However, the limitation of existing fabrication methods as difficulty to precisely manipulate chiral nanostructures at the nanoscale restricts their application and optimization of performance. In this work, we report a simple and robust route for the precise construction of chiral Au nanoparticles (NPs), employing star-like block copolymers with well-defined structures as chiral templates. The globular unimolecular micelles as nanoreactors enabled control over the size, shape, and chirality of in situ grown nanocrystals. Utilizing the chiral anisotropy property of surface-enhanced Raman scattering (SERS), the enantioselective discrimination on various substrates was accomplished with an enhancement factor over 9.3 × 106. NPs with a smaller size exhibited strengthened Raman enhancement and chiral recognition. Furthermore, these chiral unimolecular-micelle-based templates with high efficiency and strong controllability could pave the way for tailor-made chiral nanomaterials.

Tendon extracellular-matrix-derived tissue engineering micro-tissue for Achilles tendon injury regeneration in rats.

BACKGROUND: Achilles tendon is vital in maintaining the stability and function of ankle joint. It is quite difficult to achieve the structural and functional repair of Achilles tendon in tissue engineering. METHODS: A tissue-engineered tendon micro-tissue was prepared using rat tail tendon extracellular matrix (TECM) combined with rat adipose stem cells (ADSCs) to repair Achilles tendon injuries. The TECM was prepared by repeated freezing and thawing. The in vitro characteristics of TECM and its effect on ADSCs proliferation were detected. This tissue-engineered tendon micro-tissue for Achilles tendon repair in vivo was evaluated based on general characteristics, gait analysis, ultrasound findings, histological analysis, and biomechanical testing. RESULTS: The results showed that the TECM scaffold had good biocompatibility for ADSCs. At 2 weeks post-surgery, collagen types I and III and tenomodulin expression were higher, and vascular endothelial growth factor expression was lower in the micro-tissue group than other groups. At 4 and 8 weeks post-surgery, the results of histological analysis and ultrasound findings showed that the repaired tendon tissue was smooth and lustrous, and was arranged regularly and evenly in the micro-tissue group. Gait analysis confirmed that better motor function recovery was noted in micro-tissue group than other groups. In addition, the mechanical properties of the repaired tendon tissue in micro-tissue group were better than other groups. CONCLUSION: Tissue-engineered tendon micro-tissue fabricated by TECM and ADSCs has good biocompatibility and can promote structural and functional repair of tendon in vivo. This composite biomaterial has broad application prospects in tissue engineering.

Dynamic behavior of electro-osmosis in variable charge soils: Insights on termination and direction reversal.

Electro-osmosis offers an effective method for dewatering and remediating low permeability soil. Long-term observations on nonlinear behavior of electro-osmosis and the influencing factors are not commonly reported. Connection between cessation and direction reversal of electro-osmotic flow (EOF), and the evolution of electro-chemical parameters inside of the soil mass thus remains unclear. The dynamic response of EOF in variable charge soil could be significant, whereas the investigations on which are currently lacking. A series of electro-osmotic experiments were performed with two natural variable charge soils. The results indicated that initial electro-osmotic rate was positively proportional to electric current and initial electrical conductivity of the pore fluid, which could be explained by the ion migration model. The dynamic evolution of electro-osmotic rate and electro-chemical parameters corresponding to the solute and pH conditionings at the electrode compartments demonstrated that: 1) coupling effects of non-uniform distribution of voltage gradient and pH determined the magnitude and direction of EOF rate; 2) compared to the final pHIEP value, the bigger, close and smaller values of the novel index "voltage gradient weighed mean of spatial pH″ represented the forward, terminated and reversed EOF respectively; 3) the classical Helmholtz-Smoluchowski model are proved to be more applicable interpreting the coupled nonlinearity of electro-osmosis during the later steady phase. This work would facilitate future research for a comprehensive electro-osmotic model, and provide guidance to condition the initial and boundary conditions in application of electro-osmotic dewatering and electrokinetic remediation.

BaTiO3 Catalyzed Ultrasonic-Driven Piezoelectric-Induced Reversible Addition-Fragmentation Chain-Transfer Polymerization in Aqueous Media.

Compared with normal stimulus such as light and heat, ultrasonic possesses much deeper penetration into tissues and organs and has lower scattering in heterogeneous systems as a noninvasive stimulus. Reversible addition-fragmentation chain-transfer polymerization (RAFT) in aqueous media is performed in a commercial ultrasonic wash bath with 40 kHz frequency ultrasonic, in the presence of piezoelectric tetragonal BaTiO3 (BTO) nanoparticles. Owing to the electron transfer from BTO under the ultrasonic action, the water can be decomposed to produce hydroxyl radical (HO•) and initiate the RAFT polymerization (piezo-RAFT). The piezo-RAFT polymerization exhibits features of controllable and livingness, such as linear increase of molar mass and narrow molar mass distributions (Mw/Mn < 1.20). Excellent temporal control of the polymerization and the chain fidelity of polymers are illustrated by "ON and OFF" experiment and chain extension, separately. Moreover, this ultrasonic-driven piezoelectric-induced RAFT polymerization in aqueous media can be directly used for the preparation of piezoelectric hydrogel which have potential application for stress sensor.

Predicting drug-Protein interaction with deep learning framework for molecular graphs and sequences: Potential candidates against SAR-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 disease, which represents a new life-threatening disaster. Regarding viral infection, many therapeutics have been investigated to alleviate the epidemiology such as vaccines and receptor decoys. However, the continuous mutating coronavirus, especially the variants of Delta and Omicron, are tended to invalidate the therapeutic biological product. Thus, it is necessary to develop molecular entities as broad-spectrum antiviral drugs. Coronavirus replication is controlled by the viral 3-chymotrypsin-like cysteine protease (3CLpro) enzyme, which is required for the virus's life cycle. In the cases of severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV), 3CLpro has been shown to be a promising therapeutic development target. Here we proposed an attention-based deep learning framework for molecular graphs and sequences, training from the BindingDB 3CLpro dataset (114,555 compounds). After construction of such model, we conducted large-scale screening the in vivo/vitro dataset (276,003 compounds) from Zinc Database and visualize the candidate compounds with attention score. geometric-based affinity prediction was employed for validation. Finally, we established a 3CLpro-specific deep learning framework, namely GraphDPI-3CL (AUROC: 0.958) achieved superior performance beyond the existing state of the art model and discovered 10 molecules with a high binding affinity of 3CLpro and superior binding mode.

An approach based on a combination of toxicological experiments and in silico predictions to investigate the adverse outcome pathway (AOP) of paraquat neuro-immunotoxicity.

Paraquat (PQ) exposure is strongly associated with neurotoxicity. However, research on the neurotoxicity mechanisms of PQ varies in terms of endpoints of toxic assessment, resulting in a great challenge to understand the early neurotoxic effects of PQ. In this study, we developed an adverse outcome pathway (AOP) to investigate PQ-induced neuro-immunotoxicity from an immunological perspective, combining of traditional toxicology methods and computer simulations. In vivo, PQ can microstructurally lead to an early synaptic loss in the brain mice, which is a large degree regarded as a main reason for cognitive impairment to mice behavior. Both in vitro and in vivo demonstrated synapse loss is caused by excessive activation of the complement C1q/C3-CD11b pathway, which mediates microglial phagocytosis dysfunction. Additionally, the interaction between PQ and C1q was validated by molecular simulation docking. Our findings extend the AOP framework related to PQ neurotoxicity from a neuro-immunotoxic perspective, highlighting C1q activation as the initiating event for PQ-induced neuro-immunotoxicity. In addition, downstream complement cascades induce abnormal microglial phagocytosis, resulting in reduced synaptic density and subsequent non-motor dysfunction. These findings deepen our understanding of neurotoxicity and provide a theoretical basis for ecological risk assessment of PQ.

Association of serum AFP trajectories and hepatocellular carcinoma outcomes after hepatic arterial infusion chemotherapy: A longitudinal, multicenter study.

AIM: This study aims to investigate α-fetoprotein (AFP) trajectories for prediction of survival outcomes after hepatic arterial infusion chemotherapy (HAIC) treatment in large hepatocellular carcinoma (HCC). METHODS: From May 2014 to June 2020, 889 eligible patients with large HCC underwent HAIC were retrospectively enrolled from five hospitals. A latent class growth mixed (LCGM) model was applied to distinguish potential AFP level dynamic changing trajectories. Inverse-probability-of-treatment weighted (IPTW) analyses were performed to eliminate unmeasured confounders through marginal structural models. Multivariate Cox proportional hazard regression analyses were used to determine the overall survival (OS) in patients with large HCC. Performance of these serum markers for survival prediction was compared by areas under receiver operating characteristic analysis with the Delong test. RESULTS: The median follow-up time was 23.7 (interquartile range, 3.8-115.3). A total of 1009 patients with large HCC, who underwent HAIC with AFP repeatedly measured 3-10 times, were enrolled in the study. Three distinct trajectories of these serum AFP were identified using the LCGM model: high stable (37.0%; n = 373), low stable (15.7%; n = 159), and sharp-falling (47.3%; n = 477). Multivariate Cox proportional hazard regression analyses found that ALBI stage 2-3, BCLC-C stage and high-stable AFP trajectories were associated with OS. AFP trajectories yield the optimal predictive performance in all risk factors. CONCLUSIONS: The AFP trajectories based on longitudinal AFP change showed outstanding performance for predicting survival outcomes after HAIC treatment in large HCC, which provide a potential monitoring tool for improving clinical decision-making.

Ru(II) Oligothienyl Complexes with Fluorinated Ligands: Photophysical, Electrochemical, and Photobiological Properties.

A series of Ru(II) complexes incorporating two 4,4'-bis(trifluoromethyl)-2,2'-bipyridine (4,4'-btfmb) coligands and thienyl-appended imidazo[4,5-f][1,10]phenanthroline (IP-nT) ligands was characterized and assessed for phototherapy effects toward cancer cells. The [Ru(4,4'-btfmb)2(IP-nT)]2+ scaffold has greater overall redox activity compared to Ru(II) polypyridyl complexes such as [Ru(bpy)3]2+. Ru-1T-Ru-4T have additional oxidations due to the nT group and additional reductions due to the 4,4'-btfmb ligands. Ru-2T-Ru-4T also exhibit nT-based reductions. Ru-4T exhibits two oxidations and eight reductions within the potential window of -3 to +1.5 V. The lowest-lying triplets (T1) for Ru-0T-2T are metal-to-ligand charge-transfer (3MLCT) excited states with lifetimes around 1 µs, whereas T1 for Ru-3T-4T is longer-lived (∼20-24 µs) and of significant intraligand charge-transfer (3ILCT) character. Phototoxicity toward melanoma cells (SK-MEL-28) increases with n, with Ru-4T having a visible EC50 value as low as 9 nM and PI as large as 12,000. Ru-3T and Ru-4T retain some of this activity in hypoxia, where Ru-4T has a visible EC50 as low as 35 nM and PI as high as 2900. Activity over six biological replicates is consistent and within an order of magnitude. These results demonstrate the importance of lowest-lying 3ILCT states for phototoxicity and maintaining activity in hypoxia.

Confined Unimolecular Micelles for Directed Self-Assembly of Ultrastable Multiple-Responsive Ratiometric Fluorescent Ultrasmall Nanoparticle Assemblies.

Ultrasmall fluorescent nanomaterials have been widely studied as novel fluorescent probes; however, these nanomaterials are prone to structural damage or aggregation, and the sensitivity and accuracy of most single emission fluorescence probes were very low. Therefore, the controlled synthesis of stable dual-emission ratiometric fluorescence ultrasmall assembly probes still remains a challenge. Herein, star-like polymer unimolecular micelles were utilized as a scaffold template to encapsulate fluorescent ultrasmall carbon quantum dots (CQDs) and gold nanoclusters (AuNCs) via the polymer template directed self-assembly strategy to obtain multiple-responsive ratiometric fluorescent assemblies. The assemblies were ultrastable, well-defined, and nearly monodispersed with controlled size, regular morphology, and pH- and thermal-responsiveness. The assemblies can be applied to realize rapid, sensitive, quantitative, and specific detection of Cu2+ and GSH. Moreover, the convenient rapid real-time detection was realized via the combination of the visualized paper-based sensor, and the multilevel information encryption was also achieved.

A double-network porous hydrogel based on high internal phase emulsions as a vehicle for potassium sucrose octasulfate delivery accelerates diabetic wound healing.

Diabetic wounds are a difficult medical challenge. Excessive secretion of matrix metalloproteinase-9 (MMP-9) in diabetic wounds further degrades the extracellular matrix and growth factors and causes severe vascular damage, which seriously hinders diabetic wound healing. To solve these issues, a double-network porous hydrogel composed of poly (methyl methacrylate-co-acrylamide) (p(MMA-co-AM)) and polyvinyl alcohol (PVA) was constructed by the high internal phase emulsion (HIPE) technique for the delivery of potassium sucrose octasulfate (PSO), a drug that can inhibit MMPs, increase angiogenesis and improve microcirculation. The hydrogel possessed a typical polyHIPE hierarchical microstructure with interconnected porous morphologies, high porosity, high specific surface area, excellent mechanical properties and suitable swelling properties. Meanwhile, the p(MMA-co-AM)/PVA@PSO hydrogel showed high drug-loading performance and effective PSO release. In addition, both in vitro and in vivo studies showed that the p(MMA-co-AM)/PVA@PSO hydrogel had good biocompatibility and significantly accelerated diabetic wound healing by inhibiting excessive MMP-9 in diabetic wounds, increasing growth factor secretion, improving vascularization, increasing collagen deposition and promoting re-epithelialization. Therefore, this study provided a reliable therapeutic strategy for diabetic wound healing, some theoretical basis and new insights for the rational design and preparation of wound hydrogel dressings with high porosity, high drug-loading performance and excellent mechanical properties.

Carbon Fiber Film with Multi-Hollow Channels to Expedite Oxygen Electrocatalytic Reaction Kinetics for Flexible Zn-Air Battery.

The high oxygen electrocatalytic overpotential of flexible cathodes due to sluggish reaction kinetics result in low energy conversion efficiency of wearable zinc-air batteries (ZABs). Herein, lignin, as a 3D flexible carbon-rich macromolecule, is employed for partial replacement of polyacrylonitrile and constructing flexible freestanding air electrodes (FFAEs) with large amount of mesopores and multi-hollow channels via electrospinning combined with annealing strategy. The presence of lignin with disordered structure decreases the graphitization of carbon fibers, increases the structural defects, and optimizes the pore structure, facilitating the enhancement of electron-transfer kinetics. This unique structure effectively improves the accessibility of graphitic-N/pyridinic-N with oxygen reduction reaction (ORR) activity and pyridinic-N with oxygen evolution reaction (OER) activity for FFAEs, accelerating the mass transfer process of oxygen-active species. The resulting N-doped hollow carbon fiber films (NHCFs) exhibit superior bifunctional ORR/OER performance with a low potential difference of only 0.60 V. The rechargeable ZABs with NHCFs as metal-free cathodes possess a long-term cycling stability. Furthermore, the NHCFs can be used as FFAEs for flexible ZABs which have a high specific capacity and good cycling stability under different bending states. This work paves the way to design and produce highly active metal-free bifunctional FFAEs for electrochemical energy devices.

Enhancing Security in Visible Light Communication: A Tabu-Search-Based Method for Transmitter Selection.

In this paper, we explore the secrecy performance of a visible light communication (VLC) system consisting of distributed light-emitting diodes (LEDs) and multiple users (UEs) randomly positioned within an indoor environment while considering the presence of an eavesdropper. To enhance the confidentiality of the system, we formulate a problem of maximizing the sum secrecy rate for UEs by searching for an optimal LED for each UE. Due to the non-convex and non-continuous nature of this security maximization problem, we propose an LED selection algorithm based on tabu search to avoid getting trapped in local optima and expedite the search process by managing trial vectors from previous iterations. Moreover, we introduce three LED selection strategies with a low computational complexity. The simulation results demonstrate that the proposed algorithm achieves a secrecy performance very close to the global optimal value, with a gap of less than 1%. Additionally, the proposed strategies exhibit a performance gap of 28% compared to the global optimal.

Bioinspired wet adhesive carboxymethyl cellulose-based hydrogel with rapid shape adaptability and antioxidant activity for diabetic wound repair.

Currently, adhesive hydrogels have shown promising effect in chronic diabetic wound repair. However, there are issues and challenges in treating diabetic wounds due to inadequate wet adhesion, unable to fill irregular and deep wounds, and oxidative stress. Herein, a mussel-inspired naturally hydrogel dressing with rapid shape adaptability, wet adhesion and antioxidant abilities for irregular, deep and frequently movement diabetic wounds repair was constructed by comprising catechol modified carboxymethyl cellulose (CMC-DA) and tannic acid. Benefiting from the reversible hydrogen bonding, the resulting hydrogels exhibited injectability, remarkable self-healing ability, rapid shape adaptability and strong tissue adhesion (45.9 kPa), thereby contributing to self-adaptive irregular-shaped wounds or moving joint parts. Especially, the adhesion strength of the hydrogel on wet tissue still remained at 14.9 kPa. Besides, the hydrogels could be easily detached from the skin by ice-cooling that avoided secondary damage caused by dressing change. Remarkably, the hydrogels possessed excellent antioxidant, satisfactory biocompatibility, efficient hemostasis and antibacterial properties. The in vivo evaluation further demonstrated that the hydrogel possessed considerable wound-healing promotion effect by regulating diabetic microenvironment, attributed to that the hydrogel could significantly reduce inflammatory response, alleviate oxidative stress and regulate neovascularization. Overall, this biosafe adhesive hydrogel had great potentials for diabetic wound management.

A potential mechanism clue to the periodic storm from microglia activation and progressive neuron damage induced by paraquat exposure.

Paraquat (PQ), is characterized by neurotoxicity, which increases the potential risk of Parkinson's disease (PD) exposure in the long-term and low doses. Triggering microglia activation and neuroinflammation is deemed an early event resulting in PD. However, the underlying pathogenesis of PD by PQ is not clear yet. In this article, C57BL/6J mice treated with PQ could successfully act out Parkinson-like. In addition, we observed the fluorescence intensity enhancement of Iba-1 activated microglia with released pro-inflammatory, all ahead of both the damage of dopaminergic neurons in the substantia nigra and corpus striatum of the brain. Surprisingly, the injection of minocycline before PQ for many hours not only can effectively improve the neurobehavioral symptoms of mice but inhibit the activation of microglia and the release of pro-inflammatory substances, even controlling the gradual damage and loss of neurons. A further mechanism of minocycline hampered the expression levels of key signaling proteins PI3K, PDK1, p-AKT, and CD11b (the receptor of microglia membrane recognition), while a large number of inflammatory factors. Our results suggested that the CD11b/PI3K/NOX2 pathway may be a clue that microglia-mediated inflammatory responses and neuronal damage in a PQ-induced abnormal behavior Parkinson-like mouse.

Building Your Future Holographic Mentor: Can We Use Mixed Reality Holograms for Visual Spatial Motor Skills Acquisition in Surgical Education?

Learning surgical skills require critical visual-spatial motor skills. Current learning methods employ costly and limited in-person teaching in addition to supplementation by videos, textbooks, and cadaveric labs. Increasingly limited healthcare resources and in-person training has led to growing concerns for skills acquisition of trainees. Recent Mixed Reality (MR) devices offer an attractive solution to these resource barriers by providing three-dimensional holographic representations of reality that mimic in-person experiences in a portable, individualized, and cost-effective form. We developed and evaluated two holographic MR models to explore the feasibility of visual-spatial motor skill acquisition from a technical development, learning, and usability perspective. In our first, a pair of holographic hands were created and projected in front of the trainee, and participants were evaluated on their ability to learn complex hand motions in comparison to traditional methods of video and apprenticeship-based learning. The second model displayed a 3D holographic model of the middle and inner ear with labeled anatomical structures which users could explore and user experience feedback was obtained. Our studies demonstrated that scores between MR and apprenticeship learning were comparable. All felt MR was an effective learning tool and most noted that the MR models were better than existing didactic methods of learning. Identified advantages of MR included the ability to provide true 3D spatial representation, improved visualization of smaller structures in detail by upscaling the models, and improved interactivity. Our results demonstrate that holographic learning is able to mimic in-person learning for visual-spatial motor skills and could be a new effective form of self-directed apprenticeship learning.

Systematic review of the risk of urolithiasis following parathyroidectomy in patients with primary hyperparathyroidism.

OBJECTIVE: Parathyroidectomy (PTX) is the conclusive therapy for primary hyperparathyroidism (PHPT), but its effect on the risk of urolithiasis is inconclusive. We comprehensively reviewed the currently available research to investigate the impact of PTX on the likelihood of urolithiasis among individuals suffering PHPT. METHODS: Internet-based articles in English language released on Cochrane, PubMed, Scopus, Web of knowledge, and Embase up to September, 2023 were comprehensively reviewed. Each publication in contrast to the incidence, occurrence, or recurrence of urolithiasis after PTX versus medical treatment in PHPT patients was included. The outcome with pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) was examined employing DerSimonian and Laird's model of random effects. To determine the range of the real effect size of a future study in 95% of all populations, a prediction interval (PI) was also established. RESULTS: Finally, ten studies involving 74,190 patients were included. Results from randomized-controlled trials (RCTs) and observational studies (OSs) both revealed that PTX did not substantially lessen the vulnerability of urolithiasis among individuals with PHPT (RCTs: pooled relative risk [RR] 0.42, 95%CI 0.13-1.41, p = 0.163; OSs: pooled RR 1.37, 95%CI 0.96 to 1.97, p = 0.084). The PI (RCT: 0.03 to 5.96; OSs: 0.44-4.20) containing 1.0 suggested the possibility of consistent results in future studies. Subgroup and sensitivity analyses supported the above findings, and no evidence showed publication bias. CONCLUSION: Our analysis from the available RCTs or OSs did not give adequate or exact proof that the average effect of PTX lowers the incidence of urolithiasis among PHPT persons based on the random-effects model. Future research shall take into account the common effect of PTX as well as the prerequisites of preventive stone procedures, which will further help us assess the effectiveness of PTX in reducing kidney calculus comorbidity and develop techniques to avoid stone sequelae in these individuals.

Combatting ageing in dermal papilla cells and promoting hair follicle regeneration using exosomes from human hair follicle dermal sheath cup cells.

Dermal papilla cells (DPCs) undergo premature ageing in androgenetic alopecia and senescent alopecia. As critical components of hair follicle reconstruction, DPCs are also prone to senescence in vitro, resulting in a diminished hair follicle inductivity capacity. Dermal sheath cup cells (DSCCs), a specific subset of hair follicle mesenchymal stem cells, intimately linked to the function of DPCs. The primary objective of this research is to investigate the anti-ageing effect of exosomes derived from DSCCs (ExoDSCCs ) on DPCs. Exosomes were utilized to treat H2 O2 -induced DPCs or long-generation DPCs(P10). Our findings demonstrate that ExoDSCCs(P3) promote the proliferation, viability and migration of senescent DPCs while inhibiting cell apoptosis. The expression of senescence marker SA-ß-Gal were significantly downregulated in senescent DPCs. When treated with ExoDSCCs(P3) , expression of inducibility related markers alkaline phosphatase and Versican were significantly upregulated. Additionally, ExoDSCCs(P3) activated the Wnt/ß-catenin signalling in vitro. In patch assay, ExoDSCCs(P3) significantly promoted hair follicle reconstruction in senescent DPCs. In summary, our work highlights that ExoDSCCs(P3) may restore the biological functions and improve the hair follicle induction ability of senescent DPCs. Therefore, ExoDSCCs(P3) may represent a new strategy for intervening in the ageing process of DPCs, contributing to the prevention of senile alopecia.