Therapeutic analysis of laser moxibustion for different KL graded knee osteoarthritis.

BACKGROUND: Our previous studies showed that laser moxibustion may be effective in alleviating the symptoms of knee osteoarthritis. However, the therapeutic effect in patients with different Kellgren-Lawrence (KL) grades is still unclear. We aimed to compare the efficacy of laser moxibustion in the treatment of knee osteoarthritis with different KL grades. METHODS: A total of 392 symptomatic KOA patients with different KL grades were randomly assigned to the laser treatment or sham laser control group (1:1). The patients received laser moxibustion treatment or sham treatment 3 times a week for 4 weeks. Outcomes were measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores and Visual Analog Scale (VAS) scores, and the primary outcome measurement was the change in WOMAC pain scores from baseline to week 4. RESULTS: Among 392 randomized participants, 364 (92.86%) completed the trial. Participants with KL grades 2, 3, and 4 had significantly higher pain, functional, and total WOMAC scores than those with KL grade 1. Spearman correlation test results showed a positive correlation between KL grade and WOMAC pain, function, stiffness scores, and WOMAC total scores. That is, the higher the KL grade, the higher the WOMAC pain, function, stiffness, and WOMAC total scores. After 4 weeks of treatment, patients with KL grades 2 and 3 had significantly higher improvement scores in pain, function, and total scores than those with KL grade 1, whereas those with KL grade 2 had significantly higher improvement scores in stiffness than those with KL grade 1. Patients with KL grade 4 showed no significant effects after laser moxibustion treatment. CONCLUSION: Laser moxibustion is effective for pain reduction and functional improvement in the treatment of KOA with KL grades 2 and 3.

Assessing the necessity of screening ≤5 Mb segmental aneuploidy in routine PGT for aneuploidies.

RESEARCH QUESTION: Does routine clinical practice require an increase in the resolution of preimplantation genetic testing for aneuploidies (PGT-A) to detect segmental aneuploidies ≤5 Mb? DESIGN: This retrospective study analysed 963 trophectoderm biopsies from 346 couples undergoing PGT between 2019 and 2023. Segmental aneuploidies ≥1 Mb were reported. The characteristics, clinical interpretation and concordance of segmental aneuploidies ≤5 Mb were analysed. RESULTS: The incidence of segmental aneuploidies was 15.1% (145/963) in blastocysts, with segmental aneuploidies of ≤5 Mb accounting for 2.3% (22/963). The size of the segmental aneuploidies showed a skewed distribution. Segmental aneuploidies ≤5 Mb were found to occur more frequently on the q arm of the chromosome, compared with the p arm. Losses of ≤5 Mb segmental aneuploidies were more prevalent than gains, with 17 deletions compared with 5 duplications. Of the segmental aneuploidies, 63.6% (14/22) ≤5 Mb were de novo, and 50.0% (7/14) of de-novo segmental aneuploidies were pathogenic/likely pathogenic (P/LP) copy number variations, accounting for 0.7% of 963 blastocysts. For blastocysts carrying ≤5 Mb segmental aneuploidies, a re-analysis of back-up biopsy samples showed that 35.7% of de-novo segmental aneuploidies (5/14) were not detected in the back-up samples. Cases were reported in which prenatal diagnosis (amniocentesis) revealed the absence of embryonic ≤5 Mb segmental aneuploidies detected at the blastocyst stage. CONCLUSIONS: The incidence of P/LP de-novo ≤5 Mb segmental aneuploidies in human blastocysts is extremely low. There is no compelling need to increase the resolution of PGT-A to 5 Mb in routine clinical practice.

Polymer Fiber Rigid Network with High Glass Transition Temperature Reinforces Stability of Organic Photovoltaics.

Organic photovoltaics (OPVs) need to overcome limitations such as insufficient thermal stability to be commercialized. The reported approaches to improve stability either rely on the development of new materials or on tailoring the donor/acceptor morphology, however, exhibiting limited applicability. Therefore, it is timely to develop an easy method to enhance thermal stability without having to develop new donor/acceptor materials or donor-acceptor compatibilizers, or by introducing another third component. Herein, a unique approach is presented, based on constructing a polymer fiber rigid network with a high glass transition temperature (Tg) to impede the movement of acceptor and donor molecules, to immobilize the active layer morphology, and thereby to improve thermal stability. A high-Tg one-dimensional aramid nanofiber (ANF) is utilized for network construction. Inverted OPVs with ANF network yield superior thermal stability compared to the ANF-free counterpart. The ANF network-incorporated active layer demonstrates significantly more stable morphology than the ANF-free counterpart, thereby leaving fundamental processes such as charge separation, transport, and collection, determining the device efficiency, largely unaltered. This strategy is also successfully applied to other photovoltaic systems. The strategy of incorporating a polymer fiber rigid network with high Tg offers a distinct perspective addressing the challenge of thermal instability with simplicity and universality.

Mechanism of Reactive Oxygen/Nitrogen Species in Liver Ischemia-Reperfusion Injury and Preventive Effect of Chinese Medicine.

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.

Toxicity of the sunscreen UV filter benzophenone-3 (OBZ) to the microalga Selenastrum capricornutum: An insight into OBZ's damage to photosynthesis and respiration.

Oxybenzone (OBZ; benzophenone-3, CAS# 131-57-7), as a new pollutant and ultraviolet absorbent, shows a significant threat to the survival of phytoplankton. This study aims to explore the acute toxic effects of OBZ on the growth of the microalga Selenastrum capricornutum, as well as the mechanisms for its damage to the primary metabolic pathways of photosynthesis and respiration. The results demonstrated that the concentrations for 50 % of maximal effect (EC50) of OBZ for S. capricornutum were 9.07 mg L-1 and 8.54 mg L-1 at 72 h and 96 h, respectively. A dosage of 4.56 mg L-1 OBZ significantly lowered the photosynthetic oxygen evolution rate of S. capricornutum in both light and dark conditions for a duration of 2 h, while it had no effect on the respiratory oxygen consumption rate under darkness. OBZ caused a significant decline in the efficiency of photosynthetic electron transport due to its damage to photosystem II (PSII), thereby decreasing the photosynthetic oxygen evolution rate. Over-accumulated H2O2 was produced under light due to the damage caused by OBZ to the donor and acceptor sides of PSII, resulting in increased peroxidation of cytomembranes and inhibition of algal respiration. OBZ's damage to photosynthesis and respiration will hinder the conversion and reuse of energy in algal cells, which is an important reason that OBZ has toxic effects on S. capricornutum. The present study indicated that OBZ has an acute toxic effect on the microalga S. capricornutum. In the two most important primary metabolic pathways in algae, photosynthesis is more sensitive to the toxicity of OBZ than respiration, especially in the dark.

Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study.

OBJECTIVE: To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients. METHODS: This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias. RESULTS: A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001). CONCLUSIONS: In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285).

An all-in-one tetrazine reagent for cysteine-selective labeling and bioorthogonal activable prodrug construction.

The prodrug design strategy offers a potent solution for improving therapeutic index and expanding drug targets. However, current prodrug activation designs are mainly responsive to endogenous stimuli, resulting in unintended drug release and systemic toxicity. In this study, we introduce 3-vinyl-6-oxymethyl-tetrazine (voTz) as an all-in-one reagent for modular preparation of tetrazine-caged prodrugs and chemoselective labeling peptides to produce bioorthogonal activable peptide-prodrug conjugates. These stable prodrugs can selectively bind to target cells, facilitating cellular uptake. Subsequent bioorthogonal cleavage reactions trigger prodrug activation, significantly boosting potency against tumor cells while maintaining exceptional off-target safety for normal cells. In vivo studies demonstrate the therapeutic efficacy and safety of this prodrug design approach. Given the broad applicability of functional groups and labeling versatility with voTz, we foresee that this strategy will offer a versatile solution to enhance the therapeutic range of cytotoxic agents and facilitate the development of bioorthogonal activatable biopharmaceuticals and biomaterials.

A synergistically antimicrobial and antioxidant hyaluronic acid hydrogel for infected wounds.

Bacterial infections during wound healing impede the healing process and trigger local or systemic inflammatory reactions. Consequently, there is an urgent need to develop a new material with antimicrobial and antioxidant properties to promote infected wound healing. A synergistically antimicrobial and antioxidant hyaluronic acid hydrogel (HMn) is prepared by employing MnO2 nanosheets into 4ARM-PEG5000-SH crosslinked methacrylated hyaluronic acid (HAMA) network. The coordination between sulfhydryl groups of 4ARM-PEG5000-SH and MnO2 nanosheets ensures entrapment of the nanosheets within the hydrogel, while the interaction between 4ARM-PEG5000-SH and HAMA results in facile gelation through thiol-ene click reaction. MnO2 nanosheets exhibit strong photothermal properties and reactive oxygen species (ROS) scavenging abilities, while hyaluronic acid promotes wound healing. When subjected to near-infrared (NIR) irradiation, the HMn achieves a bactericidal rate of 95.24 % for Staphylococcus aureus and nearly 100 % for Escherichia coli. In animal experiments, treatment with the HMn under NIR irradiation results in the best wound healing outcomes. Both in vitro and vivo biocompatible assays demonstrate that the HMn has rarely cell cytotoxicity and tissue damage. The HMn is easy to prepare and has good biocompatibility as well as efficient antibacterial and antioxidant properties, providing a novel method for the treatment of infected wounds.

Nose-to-brain delivery of nanotherapeutics: Transport mechanisms and applications.

The blood-brain barrier presents a key limitation to the administration of therapeutic molecules for the treatment of brain disease. While drugs administered orally or intravenously must cross this barrier to reach brain targets, the unique anatomical structure of the olfactory system provides a route to deliver drugs directly to the brain. Entering the brain via receptor, carrier, and adsorption-mediated transcytosis in the nasal olfactory and trigeminal regions has the potential to increase drug delivery. In this review, we introduce the physiological and anatomical structures of the nasal cavity, and summarize the possible modes of transport and the relevant receptors and carriers in the nose-to-brain pathway. Additionally, we provide examples of nanotherapeutics developed for intranasal drug delivery to the brain. Further development of nanoparticles that can be applied to intranasal delivery systems promises to improve drug efficacy and reduce drug resistance and adverse effects by increasing molecular access to the brain. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease.

Regulating nitrogen/sulfur terminals on 3D porous Ti3C2 MXene with enhanced reaction kinetics toward high-performance alkali metal ion storage.

In this paper, we have developed a simple and efficient sulfur-amine chemistry strategy to prepare a three-dimensional (3D) porous Ti3C2Tx composite with large amounts of N and S terminal groups. The well-designed 3D macroporous architecture presents enlarged interlayer spacing, large specific surface area, and unique porous structure, which successfully solves the re-stacking issue of MXene during storage and electrode fabrication. It is the amount of concentrated hydrochloric acid added to the S-EDA (ethylenediamine)/MXene colloidal suspension that is critical to the formation of 3D morphology. In addition, N and S terminals on MXene could improve the adsorption ability of K+. Owing to the synergistic effect of the structure design and terminal modification, the N, S codoped three-dimensional porous Ti3C2Tx (3D-NSPM) material shows a high surface capacitive contribution and rapid diffusion kinetics for K+ and Na+. As a result, the as-prepared 3D-NSPM delivers high reversible capacity (237 and 273 mAh g-1 at 0.1 A g-1 for PIBs and SIBs, respectively), superb cycling stability (84.9% capacity retention after 10,000 cycles at 1 A g-1 in PIBs and 74.0% capacity retention after 2200 cycles at 1 A g-1 in SIBs), and excellent rate capability (111 and 196 mAh g-1 at 5 A g-1 for PIBs and SIBs, respectively), which are superior to other MXene-based anodes for PIBs and SIBs. Moreover, the described strategy provides a new insight for constructing the 3D porous structure from 2D building blocks beyond MXene.

Experiences of returning to work in patients with schizophrenia after treatment: A longitudinal qualitative study.

BACKGROUND: Returning to work (RTW) has always been regarded as one of the important indicators to evaluate the therapeutic effect of patients with schizophrenia. The existing studies on RTW in patients with schizophrenia are mostly focused on intervention measures, and the qualitative research on RTW is very limited. The purpose of this study was to evaluate the experience of the RTW after treatment in patients with schizophrenia. METHOD: A longitudinal qualitative study was conducted involving 24 patients with schizophrenia in China. The interviews were held at three time-points during their RTW process, (1) when patients had improved and were close to discharge, (2) within 1 month post-discharge, and (3) 6 months post-discharge. The interview recordings were transcribed by the research team, and transcripts were independently analyzed by two independent coders using reflexive thematic analysis. RESULTS: A total of 24 patients with schizophrenia participated in 72 personal interviews. The thematic framework based on the experience of patients with schizophrenia reveals a three-phases of the process of RTW: improved, being at a loss, and job crisis. The study identified one theme of the first phase: the expectation and optimism. Two themes in the second phase: (1) psychological distress of upcoming work; (2) expectation of assistance pre-work. And four themes in the third phase: (1) tremendous pressure of RTW; (2) lack of medical and social support; (3) social status and interpersonal relationships change; and (4) high level of financial pressure. CONCLUSION: The experience of RTW is a dynamic process with great challenges in each phase, patients with schizophrenia have been deeply affected by what they have experienced. There is an urgent need to ensure that existing community and social support is integrated into daily care to support patients with schizophrenia to RTW successful. The findings of this study also suggest relevant departments and employers should be aware of the barriers to RTW for patients with schizophrenia, and take certain measures to change the current situation.

Interactions between nanoparticles and pathological changes of vascular in Alzheimer's disease.

Emerging evidence suggests that vascular pathological changes play a pivotal role in the pathogenesis of Alzheimer's disease (AD). The dysfunction of the cerebral vasculature occurs in the early course of AD, characterized by alterations in vascular morphology, diminished cerebral blood flow (CBF), impairment of the neurovascular unit (NVU), vasculature inflammation, and cerebral amyloid angiopathy. Vascular dysfunction not only facilitates the influx of neurotoxic substances into the brain, triggering inflammation and immune responses but also hampers the efflux of toxic proteins such as Aß from the brain, thereby contributing to neurodegenerative changes in AD. Furthermore, these vascular changes significantly impact drug delivery and distribution within the brain. Therefore, developing targeted delivery systems or therapeutic strategies based on vascular alterations may potentially represent a novel breakthrough in AD treatment. This review comprehensively examines various aspects of vascular alterations in AD and outlines the current interactions between nanoparticles and pathological changes of vascular.

Nanotechnology for enhanced nose-to-brain drug delivery in treating neurological diseases.

Despite the increasing global incidence of brain disorders, achieving sufficient delivery towards the central nervous system (CNS) remains a formidable challenge in terms of translating into improved clinical outcomes. The brain is highly safeguarded by physiological barriers, primarily the blood-brain barrier (BBB), which routinely excludes most therapeutics from entering the brain following systemic administration. Among various strategies investigated to circumvent this challenge, intranasal administration, a noninvasive method that bypasses the BBB to allow direct access of drugs to the CNS, has been showing promising results. Nanotechnology-based drug delivery systems, in particular, have demonstrated remarkable capacities in overcoming the challenges posed by nose-to-brain drug delivery and facilitating targeted drug accumulation within the brain while minimizing side effects of systemic distribution. This review comprehensively summarizes the barriers of nose-to-brain drug delivery, aiming to enhance our understanding of potential physiological obstacles and improve the efficacy of nasal delivery in future trials. We then highlight cutting-edge nanotechnology-based studies that enhance nose-to-brain drug delivery in three key aspects, demonstrating substantial potential for improved treatment of brain diseases. Furthermore, the attention towards clinical studies will ease the regulatory approval process for nasal administration of nanomedicines targeting brain disease.

A multifunctional composite nanoparticle with antibacterial activities, anti-inflammatory, and angiogenesis for diabetic wound healing.

The treatment of chronic diabetic wounds remains challenging due to the rapid bacterial infection, severe inflammation, and insufficient angiogenesis. To address these challenges, a novel multifunctional composite nanoparticle is developed by co-assembling antisolvent-induced co-assembling silk-fibroin ε-poly-l-Lysine nanoparticles (nSF-EPL) and further assembling nSF-EPL with polydeoxyribonucleotide (PDRN) and exosome derived from human umbilical mesenchymal stem cells (Exo). Owing to the modification of EPL, PDRN and Exo, composite nanoparticles exhibited synergistic antibacterial action, anti-inflammatory and angiogenesis, which can significantly benefit for promoting wound healing. Release results show that the composite nanoparticles exhibit long-term sustained PDRN and Exo release profiles as well as outstanding release efficiency. Furthermore, in vitro studies show that the composite nanoparticles exhibit effective antibacterial activity, thus inducing an anti-inflammatory M2 macrophages phenotype and promoting angiogenesis. In vivo research results of investigations pertaining to diabetic wound healing show that the composite nanoparticles have good anti-inflammatory and angiogenesis capabilities, which can promote granulation tissue formation, collagen deposition, wound tissue epithelialization, and significantly accelerate skin healing. This study presents a promising strategy for the clinical treatment of chronic diabetic wounds.

A bioorthogonal cell sorting strategy for isolation of desired cell phenotypes.

Here we describe a cost-effective and simplified cell sorting method using tetrazine bioorthogonal chemistry. We successfully isolated SKOV3 cells from complex mixtures, demonstrating efficacy in separating mouse lymphocytes expressing interferon and HeLa cells expressing virally transduced green fluorescent protein post-infection.

Hydrogel-Based Biosensors for Bacterial Infections.

Hydrogels are known to have the advantages such as good biodegradability, biocompatibility, and easy functionalization, making them ideal candidates for biosensors. Hydrogel-based biosensors that respond to bacteria-induced microenvironmental changes such as pH, enzymes, antigens, etc., or directly interact with bacterial surface receptors, can be applied for early diagnosis of bacterial infections, providing information for timely treatment while avoiding antibiotic abuse. Furthermore, hydrogel biosensors capable of both bacteria diagnosis and treatment will greatly facilitate the development of point-of-care monitoring of bacterial infections. In this review, the recent advancement of hydrogel-based biosensors for bacterial infection is summarized and discussed. First, the biosensors based on pH-sensitive hydrogels, bacterial-specific secretions-sensitive hydrogels, and hydrogels directly in contact with bacterial surfaces are presented. Next, hydrogel biosensors capable of detecting bacterial infection in the early stage followed by immediate on-demand treatment are discussed. Finally, the challenges and future development of hydrogel biosensors for bacterial infections are proposed.

A structural color hydrogel for diagnosis of halitosis and screening of periodontitis.

Oral pathogens can produce volatile sulfur compounds (VSCs), which is the main reason for halitosis and indicates the risk of periodontitis. High-sensitivity detection of exhaled VSCs is urgently desired for promoting the point-of-care testing (POCT) of halitosis and screening of periodontitis. However, current detection methods often require bulky and costly instruments, as well as professional training, making them impractical for widespread detection. Here, a structural color hydrogel for naked-eye detection of exhaled VSCs is presented. VSCs can reduce disulfide bonds within the network, leading to expansion of the hydrogel and thus change of the structural color. A linear detection range of 0-1 ppm with a detection limit of 61 ppb can be achieved, covering the typical VSC concentration in the breath of patients with periodontitis. Furthermore, visual and in situ monitoring of Porphyromonas gingivalis responsible for periodontitis can be realized. By integrating the hydrogels into a sensor array, the oral health conditions of patients with halitosis can be evaluated and distinguished, offering risk assessment of periodontitis. Combined with a smartphone capable of color analysis, POCT of VSCs can be achieved, providing an approach for the monitoring of halitosis and screening of periodontitis.

Inhaled SARS-CoV-2 vaccine for single-dose dry powder aerosol immunization.

The COVID-19 pandemic has fostered major advances in vaccination technologies1-4; however, there are urgent needs for vaccines that induce mucosal immune responses and for single-dose, non-invasive administration4-6. Here we develop an inhalable, single-dose, dry powder aerosol SARS-CoV-2 vaccine that induces potent systemic and mucosal immune responses. The vaccine encapsulates assembled nanoparticles comprising proteinaceous cholera toxin B subunits displaying the SARS-CoV-2 RBD antigen within microcapsules of optimal aerodynamic size, and this unique nano-micro coupled structure supports efficient alveoli delivery, sustained antigen release and antigen-presenting cell uptake, which are favourable features for the induction of immune responses. Moreover, this vaccine induces strong production of IgG and IgA, as well as a local T cell response, collectively conferring effective protection against SARS-CoV-2 in mice, hamsters and nonhuman primates. Finally, we also demonstrate a mosaic iteration of the vaccine that co-displays ancestral and Omicron antigens, extending the breadth of antibody response against co-circulating strains and transmission of the Omicron variant. These findings support the use of this inhaled vaccine as a promising multivalent platform for fighting COVID-19 and other respiratory infectious diseases.

Intranasal mask for protecting the respiratory tract against viral aerosols.

The spread of many infectious diseases relies on aerosol transmission to the respiratory tract. Here we design an intranasal mask comprising a positively-charged thermosensitive hydrogel and cell-derived micro-sized vesicles with a specific viral receptor. We show that the positively charged hydrogel intercepts negatively charged viral aerosols, while the viral receptor on vesicles mediates the entrapment of viruses for inactivation. We demonstrate that when displaying matched viral receptors, the intranasal masks protect the nasal cavity and lung of mice from either severe acute respiratory syndrome coronavirus 2 or influenza A virus. With computerized tomography images of human nasal cavity, we further conduct computational fluid dynamics simulation and three-dimensional printing of an anatomically accurate human nasal cavity, which is connected to human lung organoids to generate a human respiratory tract model. Both simulative and experimental results support the suitability of intranasal masks in humans, as the likelihood of viral respiratory infections induced by different variant strains is dramatically reduced.