Chinese herbal medicine and acupuncture for insomnia in stroke patients: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Insomnia is highly prevalent in stroke patients; however, there is no ideal intervention. This systematic review examined the effect and safety of Chinese herbal medicine (CHM) and acupuncture on sleep in adults with stroke. METHODS: Six databases were searched from inception to June 2023 to identify randomised controlled trials (RCTs). The primary outcome was Pittsburgh Sleep Quality Index (PSQI) scores. Risk of bias and evidence quality was assessed. A pairwise random-effect meta-analysis was performed. RESULTS: A total of 54 RCTs published in 55 articles were finally included in the systematic review, including 35 of CHM and 19 of acupuncture therapies. Compared with placebo/sham procedure, CHM and acupuncture were more effective in improving PSQI scores. The evidence of moderate quality suggested that CHM outperformed benzodiazepine drugs (BZDs) while it presented an effect similar to that of non-BZDs in improving sleep quality. CHM and acupuncture also provided additional benefits to the patients treated with pharmacological agents alone. However, the evidence specific to individual CHM prescriptions lay in various factors and methodological quality, and the evidence on the comparative effectiveness between acupuncture and other therapies was conflicting or limited. CONCLUSIONS: Overall, CHM and acupuncture used alone or in combination with pharmacotherapy can safely improve sleep in stroke patients with insomnia. In the future, RCTs on outstanding CHM prescriptions and the comparative effectiveness research between acupuncture and other therapies are needed. REGISTRATION: PROSPERO No. CRD42020194029 and No. CRD42020194030.

Antitumor effects of polydopamine coated hydroxyapatite nanoparticles and its mechanism: Mitochondria-targeted ROS and calcium channels.

Nano hydroxyapatite (nHA) has been acknowledged for its inhibition efficiency on tumor cells and its excellent biocompatibility for normal tissue and cells. However, the low inhibitory efficiency of tumor cells and the ambiguous inhibitory mechanism limited its further application. In this work, four kinds of nHA with different sizes was prepared, and the one with the highest inhibition efficiency on 4T1 cells was screened as a substrate for developing the nanoparticles coated with polydopamine (PDA) coating, which was named nHA-PDA. Both in vivo and in vitro experiments were employed, and the results showed significantly higher inhibitory activity against 4T1 cells and 4T1-bared tumors by nHA-PDA. Further investigation revealed that the oxidative stress induced by PDA results in a large Reactive Oxygen Species (ROS) accumulation, thus triggering the mitochondria-dependent apoptosis pathway ROS-JNK/MAPK and inducing the cascade reaction of inhibiting the anti-apoptosis protein-Bcl-2 expression and activating the expression of the critical genes in apoptosis signaling pathway (caspase 3 and caspase 9). Besides, the significant increase of intracellular [Ca2+] may also be an essential reason for the damage of mitochondria, eventually leading to apoptosis.

Photo-methanification of aquatic dissolved organic matters with different origins under aerobic conditions: Non-negligible role of hydroxyl radicals.

Lingering inconsistencies in the global methane (CH4) budget and ambiguity in CH4 sources and sinks triggered efforts to identify new CH4 formation pathways in natural ecosystems. Herein, we reported a novel mechanism of light-induced generation of hydroxyl radicals (•OH) that drove the production of CH4 from aquatic dissolved organic matters (DOMs) under ambient conditions. A total of five DOM samples with different origins were applied to examine their potential in photo-methanification production under aerobic conditions, presenting a wide range of CH4 production rates from 3.57 × 10-3 to 5.90 × 10-2 nmol CH4 mg-C-1 h-1. Experiments of •OH generator and scavenger indicated that the contribution of •OH to photo-methanificaiton among different DOM samples reached about 4∼42 %. In addition, Fourier transform infrared spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry showed that the carbohydrate- and lipid-like substances containing nitrogen-bonded methyl groups, methyl ester, acetyl groups, and ketones, were the potential precursors for light-induced CH4 production. Based on the experimental results and simulated calculations, the contribution of photo-methanification of aquatic DOMs to the diffusive CH4 flux across the water-air interface in a typical eutrophic shallow lake (e.g., Lake Chaohu) ranged from 0.1 % to 18.3 %. This study provides a new perspective on the pathways of CH4 formation in aquatic ecosystems and a deeper understanding on the sources and sinks of global CH4.

Nano-/micro-scaled hydroxyapatite ceramic construction and the regulation of immune-associated osteogenic differentiation.

Hydroxyapatite (HA) bioceramic is a promising substitute for bone defects, and the surface properties are major factors that influence bioactivity and osteoinductivity. In this study, two kinds of HA bioceramics with nanoscale (n-HA) and microscale (m-HA) surface topography were designed to mimic the natural bone, thus enhancing the stimulation of osteogenic differentiation and revealing the potential mechanism. Compared to m-HA, n-HA owned a larger surface roughness, a stronger wettability, and reduced hardness and indentation modulus. Based on these properties, n-HA could maintain the conformation of vitronectin better than m-HA, which may contribute to higher cellular activities and a stronger promotion of osteogenic differentiation of mesenchymal stem cells (MSCs). Further RNA sequencing analysis compared the molecular expression between n-HA and m-HA. Six hundred twenty-seven differentially expressed genes were identified in MSCs, and 17 upregulated genes and 610 downregulated genes were included when n-HA compared to m-HA. The GO cluster analysis and enriched Kyoto encyclopedia of genes and genome signaling pathways revealed a close correlation with the immune process in both upregulated (chemokine signaling pathway and cytokine-cytokine receptor interaction) and downregulated pathways (osteoclasts differentiation). It suggested that the nanoscale surface topography of HA enhanced the osteoinductivity of MSCs and could not be separated from its regulation of immune function and the retention of adsorbed protein conformation.

A CS-based composite scaffold with excellent photothermal effect and its application in full-thickness skin wound healing.

The development of natural polymer-based scaffolds with excellent biocompatibility, antibacterial activity, and blood compatibility, able to facilitate full-thickness skin wound healing, remains challenging. In this study, we have developed three chitosan (CS)-based porous scaffolds, including CS, CS/CNT (carbon nanotubes) and CS/CNT/HA (nano-hydroxyapatite, n-HA) using a freeze-drying method. All three scaffolds have a high swelling ratio, excellent antibacterial activity, outstanding cytocompatibility and blood compatibility in vitro. The introduction of CNTs exhibited an obvious increase in mechanical properties and exerts excellent photothermal response, which displays excellent healing performance as a wound dressing in mouse full-thickness skin wound model when compared to CS scaffolds. CS/CNT/HA composite scaffolds present the strongest ability to promote full-thickness cutaneous wound closure and skin regeneration, which might be ascribed to the synergistic effect of photothermal response from CNT and excellent bioactivity from n-HA. Overall, the present study indicated that CNT and n-HA can be engineered as effective constituents in wound dressings to facilitate full-thickness skin regeneration.

Gigaohm and Teraohm Resistors in Femtoamp and Picoamp Electrospray Ionization.

The femtoamp electrospray ionization (femtoESI) mode has been shown to exhibit unique characteristics that may facilitate ionization efficiency studies and experiments requiring low ion beam flux. Investigation of femtoESI was hindered by a tiny, applied voltage window of 10-100 V, beyond which ionization currents quickly jumped to nanoamps. This window was difficult to locate because the exact onset voltage fluctuates due to variations in ion source alignments. Large resistors (0.1-100 TΩ) in series effectively expanded the femtoESI applied voltage range, up to 1400 V. By swapping resistors, rapid alternation allows for the comparison of both ESI modes under the same alignment. In peptide mixtures, analytes with lower surface activity are suppressed in the nanoESI mode whereas the femtoESI mode shows signal enhancement of less surface-active species. For protein solutions, there is little change in the charge states generated but the femtoESI mode does show a decrease in the average charge state of protein peaks. Peptides and proteins analyzed in the femtoESI mode also tend to generate higher intensity sodiated peaks over protonated peaks at specific charge states compared with nanoESI mode operation.

Efficacy of acupuncture for cardiopulmonary cerebral resuscitation: A systematic review and meta-analysis.

Background: Cerebral resuscitation is one of the main therapeutic aims in the treatment of cardiac arrest (CA) patients who experience a return of spontaneous circulation (ROSC). However, the therapeutic effects of current treatments are not ideal. The purpose of this study was to evaluate the efficacy of neurological function of acupuncture combined with conventional cardiopulmonary cerebral resuscitationthe (CPCR) for patients after ROSC. Methods: Seven electronic databases and other related websites were searched to identify studies on acupuncture combined with conventional CPCR for patients after ROSC. R software was used to conduct a meta-analysis, and the outcomes that could not be pooled were analyzed using a descriptive analysis. Results: Seven RCTs involving 411 participants who had experienced ROSC were eligible for inclusion. The main acupoints were Neiguan (PC6), Shuigou (DU26), Baihui (DU20), Yongquan (KI1), and Sanyinjiao (SP6). Compared to conventional CPCR, acupuncture combined with conventional CPCR led to significantly higher Glasgow Coma Scale (GCS) scores on day 3 (mean difference (MD)=0.89, 95% CI: 0.43, 1.35, I2 = 0%), day 5 (MD = 1.21, 95% CI: 0.27, 2.15; I2 = 0%), and day 7 (MD = 1.92, 95% CI: 1.35, 2.50; I2 = 0%). Conclusion: Acupuncture-assisted conventional CPCR may have a potential role in improving neurological function in CA patients after ROSC, but the certainty of evidence is very low and more high-quality studies are required. Protocol registration: This review was registered at the International Prospective Registry of Systematic Reviews (PROSPERO): CRD42021262262.

Ultra-low current electrospray ionization of chloroform solution for the analysis of perfluorinated sulfonic acids.

RATIONALE: Femtoamp and picoamp electrospray ionization (ESI) characteristics of a nonpolar solvent were explored. The direct ESI mass spectrometry analysis of chloroform extract solution enabled rapid analysis of perfluorinated sulfonic acid analytes in drinking water. METHODS: Neat chloroform solvent and extracts were directly used in a typical wire-in ESI setup using micrometer emitter tips. Ionization currents were measured with femtoamp sensitivity while ramping the spray voltage from 0 to -5000 V. Methanol was used as a comparison to illustrate the characteristics of electrospraying chloroform. The effects of spray voltage and inlet temperature were studied. A liquid-liquid extraction workflow was developed to analyze perfluorooctanoate sulfonate (PFOS) in drinking water using an ion-trap mass spectrometer. RESULTS: The ionization onset of chloroform solution was 41 ± 17 fA at 300 V. The ionization current gradually increased with voltage while remaining below 100 pA when using voltages up to -5000 V. The ion signal of PFOS was significantly enhanced to improve the limit of detection (LoD) to 25 ppt in chloroform. Coupled with a liquid-liquid extraction workflow, LoD of 0.38-5.1 ppt and a quantitation range of 5-400 ppt were achieved for perfluorinated sulfonic compounds in 1-ml water samples. CONCLUSIONS: Femtoamp and picoamp modes expand the solvent compatibility range of ESI and can enable quantitative analysis in parts per trillion (ppt) concentrations.

DNA Nanoclusters Combined with One-Shot Radiotherapy Augment Cancer Immunotherapy Efficiency.

Immunotherapy shows immense promise for improving cancer treatment. Combining immunotherapy with radiotherapy provides a conspicuous advantage due to its enhanced abscopal effect. However, established immune tolerance mechanisms in the tumor microenvironment can hamper the generation of a sufficient abscopal effect. Herein, a type of DNA nanocluster (DNAnc) that is self-assembled by a CpG-ODNs-loaded Y-shaped double-stranded DNA vector based on the unique complementary base-pairing rules is designed. The unique structure of DNAnc makes it load more than ≈8125.5 ± 822.5 copies of CpG ODNs within one single nanostructure, which effectively increases resistance to nuclease degradation and elevates the efficiency of repolarizing macrophages to an M1-like phenotype. Mechanistic studies reveal that more DNAncs are endocytosed by macrophages in the cancer tissue and repolarized macrophages to elicit a robust abscopal effect with the accumulation of macrophages induced by radiotherapy, generating potent, long-term, and durable antitumor immunity for the inhibition of tumor metastasis and the prevention of tumor recurrence, which provides a novel strategy to boost cancer immunotherapy.

Porous BCP ceramics with nanoscale whisker structure accelerate bone regeneration by regulating inflammatory response.

Inflammation-induced by biomaterials is a critical event to determine the success and efficiency of tissue repair. Macrophages are a major population that participates the biomaterial induced inflammation. The response of macrophages depends on the characteristics of biomaterials, thus causing a cascade reaction in subsequent biological processes. In this study, porous biphase calcium phosphate (BCP) ceramics with the different surface structures were constructed to compare the effect of surface structure on bone generation potential, and further reveal the inflammation-involved mechanism. Our results demonstrated that macrophages on three ceramics showed distinct morphologies and spreading areas. The nanoscale whisker structure did induce more bone generation in the mice thigh muscle. The in vitro result revealed that nanoscale whisker structure could drive macrophage polarization towards M1-like phenotype, indicated by a higher expression of pro-inflammatory specific markers (iNOS and CCR7), and mass secretion of TNF-α. Further research indicated that additional TNF-α could promote the osteogenic differentiation of mesenchymal stem cells (MSCs). However, excess addition of TNF-α showed an opposite effect on the osteogenic differentiation of MSCs by initiating the NF-κB signaling pathway, which suppresses the osteogenesis process.

Multidimensional control of therapeutic human cell function with synthetic gene circuits.

Synthetic gene circuits that precisely control human cell function could expand the capabilities of gene- and cell-based therapies. However, platforms for developing circuits in primary human cells that drive robust functional changes in vivo and have compositions suitable for clinical use are lacking. Here, we developed synthetic zinc finger transcription regulators (synZiFTRs), which are compact and based largely on human-derived proteins. As a proof of principle, we engineered gene switches and circuits that allow precise, user-defined control over therapeutically relevant genes in primary T cells using orthogonal, US Food and Drug Administration-approved small-molecule inducers. Our circuits can instruct T cells to sequentially activate multiple cellular programs such as proliferation and antitumor activity to drive synergistic therapeutic responses. This platform should accelerate the development and clinical translation of synthetic gene circuits in diverse human cell types and contexts.

High-performance multiplex drug-gated CAR circuits.

Chimeric antigen receptor (CAR) T cells can revolutionize cancer medicine. However, overactivation, lack of tumor-specific surface markers, and antigen escape have hampered CAR T cell development. A multi-antigen targeting CAR system regulated by clinically approved pharmaceutical agents is needed. Here, we present VIPER CARs (versatile protease regulatable CARs), a collection of inducible ON and OFF switch CAR circuits engineered with a viral protease domain. We established their controllability using FDA-approved antiviral protease inhibitors in a xenograft tumor and a cytokine release syndrome mouse model. Furthermore, we benchmarked VIPER CARs against other drug-gated systems and demonstrated best-in-class performance. We showed their orthogonality in vivo using the ON VIPER CAR and OFF lenalidomide-CAR systems. Finally, we engineered several VIPER CAR circuits by combining various CAR technologies. Our multiplexed, drug-gated CAR circuits represent the next progression in CAR design capable of advanced logic and regulation for enhancing the safety of CAR T cell therapy.

The role of acupuncture and moxibustion in the treatment, prevention, and rehabilitation of patients with COVID-19: A scoping review.

Introduction: This study aims to summarize the available evidence and guideline/consensus recommendations for acupuncture and moxibustion in the treatment, prevention and rehabilitation of patients with coronavirus disease 2019 (COVID-19). Methods: A scoping review was performed. Eight electronic databases and other related websites were searched. All studies related to acupuncture and moxibustion for COVID-19 were considered. Descriptive analysis was applied to analyze the all included studies and guideline recommendations. Results: We ultimately included 131 eligible studies. The main topics of the included studies were the treatment (82.4%) and prevention (38.9%) of COVID-19. The most included studies were literature reviews (65, 49.6%), protocols of systematic reviews (20, 15.3%), and guidelines and consensuses (18, 13.7%). The 18 (13.7%) COVID-19 guidelines and consensuses included 47 recommendations on acupuncture and moxibustion, which focused on the treatment (21/47, 44.7%), rehabilitation (17/47, 36.2%) and prevention (6, 12.8%) of COVID-19 patients. Zusanli (ST36), Feishu (BL13), Guanyuan (RN4) were recommended mostly for the treatment, rehabilitation and prevention respectively. Conclusion: Acupuncture and moxibustion are effective in the treatment of COVID-19 patients to some extent. However, more high-quality of clinical trials still needed to determine the feasibility of acupuncture and moxibustion in COVID-19 patients to better guide clinical practice. Study registration: Open Science Framework Registries (Registration DOI: 10.17605/OSF.IO/Z35WN; https://osf.io/z35wn).

Traditional Chinese Medicine for Post-stroke Sleep Disorders: The Evidence Mapping of Clinical Studies.

Background and Purpose: Recently, there are a number of clinical studies on traditional Chinese medicine (TCM) for post-stroke sleep disorders (PSSDs). This study aimed to map the current clinical studies and identify gaps to inform future study agendas. Methods: PubMed, Embase, Cochrane Library, and Chinese databases, including SinoMed, CNKI, and Wanfang, were searched for clinical studies on PSSDs treated with TCM from their inception to September 2021. Evidence sources, number of studies, types of PSSDs, intervention categories, effectiveness, and quality assessment were graphically displayed. Results: The evidence map involved 810 clinical studies, of which the earliest report was dated back to 1993, and an advanced growth of the whole evidence was observed in 2012. Randomized controlled trials (RCTs) were the most common type of study design (78.15%), and post-stroke insomnia was the most common type of sleep disorders (65.80%). The benefits of Chinese herbal medicine (CHM) and acupuncture therapies for post-stroke insomnia have been widely reported in RCTs (81.60% and 75.38%, respectively). However, the benefits of CHM interventions were assessed using a global approach rather than being based on a specific formula, and the highest level of evidence supporting the effectiveness of acupuncture therapies was of low methodological quality. In addition, evidence from primary studies was insufficient in the areas of TCM for post-stroke sleep-related breathing disorders (SBDs) and Chinese mind-body exercises for post-stroke insomnia. Conclusions: PSSDs treated with TCM have been widely assessed in clinical studies. For better evidence translation, clinical trials on specific CHM interventions and high-quality systematic reviews on acupuncture for post-stroke insomnia should be conducted. For a better solution to clinical questions, TCM on SBDs after stroke and the benefits of Chinese mind-body exercises for post-stroke insomnia should be explored in future clinical studies.

A responsive fluorescent probe for detecting and imaging pyruvate kinase M2 in live cells.

In this study, we designed and tested fluorescent probe zy-2 for specific and responsive imaging of pyruvate kinase M2 (PKM2), which can be excited by 419 nm light. A 17-fold enhancement in the responsive emission upon zy-2's binding to PKM2 was observed, imaging of which was successfully recorded in a time- and concentration-dependent manner in PKM2-positive cells. Thus, we obtained a responsive fluorescent probe for the specific and sensitive detection of PKM2, which is innovative in design and applicable to the detection of cancer cells.

Organic matter biomarker and 13C NMR characteristics of soil and sediment standard reference materials from China.

Soil and sediment organic matter (OM) in terrestrial environments represent two critical organic carbon pools on Earth and are likely subject to distinct degrees of oxidation and modification. However, few studies have identified critical molecular-level characteristics that differentiate soil and sediment OM from various climate zones. Using biomarkers and solid-state 13C nuclear magnetic resonance (NMR) spectroscopy analyses, we studied the OM characteristics of 11 soil and 7 sediment standard reference materials (SRMs) originating from various geographical locations in China. Results showed significantly higher concentrations of lignin phenols in sediment OM than in soil OM, which may result from protection by higher contents of CaO and less microbial degradation in sediments. Nevertheless, the relative abundances of solvent-extractable lipids (alkanes, alkanols, and alkanoic acids) and ester-bound cutin and suberin biomarkers did not differ significantly between soil and sediment SRMs. The concentrations of lignin biomarkers decreased with increasing weathering degree of the soil, while cutin biomarkers increased with mean annual temperature and precipitation. This phenomenon was not observed in sediment SRMs. This study reveals the distinct OM characteristics between Chinese soil and sediment SRMs and provides fundamental data for future studies to link OM characteristics and functions.

Clinical Evidence on the Use of Chinese Herbal Medicine for Acute Infectious Diseases: An Overview of Systematic Reviews.

Background: Acute infectious diseases constitute the most prevalent public health emergency (PHE) in China. Chinese herbal medicine (CHM) has long been used in the treatment of acute infections, but the overall evidence of its benefit and harm has not been comprehensively and systematically evaluated. Methods: We searched CBM, CNKI, Wanfang, PubMed, Cochrane Library, embase and preprint platforms to retrieve systematic reviews (SRs) on CHM for acute infectious. Participants with COVID-19, SARS, H1N1, tuberculosis, bacillary dysentery, mumps, herpangina, hand-foot-and-mouth disease (HFMD), and other acute infectious diseases were included. Interventional group consisting of patients treated with CHM combined with Western medicine or CHM alone. The AMSTAR 2 tool was used to assess the methodological quality of the retrieved studies. Information on interventions, control measures and outcomes of the included studies was extracted, and meta-analyses were qualitatively synthesized. Results: A total of 51 SRs and meta-analyses were eligible for this overview, including 19 for COVID-19, 11 for hand-foot-and-mouth disease, 8 for severe acute respiratory syndrome (SARS), 4 for tuberculosis, 3 for mumps, 2 for bacillary dysentery, 2 for H1N1 influenza and 2 for herpangina. Six systematic reviews were of high quality, all of which were on the use of CHM for COVID-19; 24 were of moderate quality; 10 were of low quality; and 11 were of very low quality. CHM appeared to have potential benefits in improving clinical symptoms and signs for most infections with an acceptable safety profile, and the clinical evidence of the benefits of CHM for acute respiratory infections such as COVID-19, SARS and H1N1 seems more sufficient than that for other acute infections. Conclusion: Overall, CHM, both decoction and Chinese patent medicine, used alone or in combination with conventional medicine may offer potential benefits to relieving symptoms of people with acute respiratory infections. Full reporting of disease typing, staging, and severity, and intervention details is further required for a better evidence translation to the responses for PHE. Future CHM research should focus mainly on the specific aspects of respiratory infections such as its single use for mild infections, and the adjunct administration for sever infections, and individual CHM prescriptions for well-selected outcomes should be prioritized.

Conducting and characterizing femto flow electrospray ionization.

Femto flow electrospray ionization (ESI) with flow rates ranging from 240 fL min-1 to the low pico level (<10 pL min-1) was conducted and measured using a submicron emitter tip and relay ESI configuration. Signature analyte ion current intensities and profiles were observed. The obtained flow rate and ionization current enabled size calculation for initial charged nanodroplets.

A Hybrid PSO-SVM Model Based on Safety Risk Prediction for the Design Process in Metro Station Construction.

Incorporating safety risk into the design process is one of the most effective design sciences to enhance the safety of metro station construction. In such a case, the concept of Design for Safety (DFS) has attracted much attention. However, most of the current research overlooks the risk-prediction process in the application of DFS. Therefore, this paper proposes a hybrid risk-prediction framework to enhance the effectiveness of DFS in practice. Firstly, 12 influencing factors related to the safety risk of metro construction are identified by adopting the literature review method and code of construction safety management analysis. Then, a structured interview is used to collect safety risk cases of metro construction projects. Next, a developed support vector machine (SVM) model based on particle swarm optimization (PSO) is presented to predict the safety risk in metro construction, in which the multi-class SVM prediction model with an improved binary tree is designed. The results show that the average accuracy of the test sets is 85.26%, and the PSO-SVM model has a high predictive accuracy for non-linear relationship and small samples. The results show that the average accuracy of the test sets is 85.26%, and the PSO-SVM model has a high predictive accuracy for non-linear relationship and small samples. Finally, the proposed framework is applied to a case study of metro station construction. The prediction results show the PSO-SVM model is applicable and reasonable for safety risk prediction. This research also identifies the most important influencing factors to reduce the safety risk of metro station construction, which provides a guideline for the safety risk prediction of metro construction for design process.