Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

BACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

Combination of bone marrow mesenchymal stem cells and moxibustion restores cyclophosphamide-induced premature ovarian insufficiency by improving mitochondrial function and regulating mitophagy.

BACKGROUND: Premature ovarian insufficiency (POI) is a major cause of infertility. In this study, we aimed to investigate the effects of the combination of bone marrow mesenchymal stem cells (BMSCs) and moxibustion (BMSCs-MOX) on POI and evaluate the underlying mechanisms. METHODS: A POI rat model was established by injecting different doses of cyclophosphamide (Cy). The modeling of POI and the effects of the treatments were assessed by evaluating estrous cycle, serum hormone levels, ovarian weight, ovarian index, and ovarian histopathological analysis. The effects of moxibustion on BMSCs migration were evaluated by tracking DiR-labeled BMSCs and analyzing the expression of chemokines stromal cell-derived factor 1 (Sdf1) and chemokine receptor type 4 (Cxcr4). Mitochondrial function and mitophagy were assessed by measuring the levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), ATP, and the mitophagy markers (Drp1, Pink1, and Parkin). Furthermore, the mitophagy inhibitor Mdivi-1 and the mitophagy activator CCCP were used to confirm the role of mitophagy in Cy-induced ovarian injury and the underlying mechanism of combination therapy. RESULTS: A suitable rat model of POI was established using Cy injection. Compared to moxibustion or BMSCs transplantation alone, BMSCs-MOX showed improved outcomes, such as reduced estrous cycle disorders, improved ovarian weight and index, normalized serum hormone levels, increased ovarian reserve, and reduced follicle atresia. Moxibustion enhanced Sdf1 and Cxcr4 expression, promoting BMSCs migration. BMSCs-MOX reduced ROS levels; upregulated MMP and ATP levels in ovarian granulosa cells (GCs); and downregulated Drp1, Pink1, and Parkin expression in ovarian tissues. Mdivi-1 significantly mitigated mitochondrial dysfunction in ovarian GCs and improved ovarian function. CCCP inhibited the ability of BMSCs-MOX treatment to regulate mitophagy and ameliorate Cy-induced ovarian injury. CONCLUSIONS: Moxibustion enhanced the migration and homing of BMSCs following transplantation and improves their ability to repair ovarian damage. The combination of BMSCs and moxibustion effectively reduced the excessive activation of mitophagy, which helped prevent mitochondrial damage, ultimately improving ovarian function. These findings provide a novel approach for the treatment of pathological ovarian aging and offer new insights into enhancing the efficacy of stem cell therapy for POI patients.

Application of clinical value assessment of treatment protocols in guideline development: taking the WFAS Clinical Practice Guideline of Acupuncture and Moxibustion for Migraine as an example. / 治疗方案临床价值评估在指南制定中的应用.

To enhance the clinical applicability of guidelines and provide more effective guidance for clinical practice, a clinical value assessment was conducted during the development of the World Federation of Acupuncture-Moxibustion Societies (WFAS) Clinical Practice Guideline of Acupuncture and Moxibustion for Migraine, which involved the evaluation of 59 acupuncture and moxibustion treatment protocols from randomized controlled trials (RCTs). This article introduced the methodology, content and results of the clinical value assessment of RCT-based acupuncture and moxibustion treatment protocols, which involved the integration of historical and contemporary medical evidence and expert consensus. It served as a methodological reference for the future development of acupuncture and moxibustion clinical practice guidelines.

Myricetin suppresses TGF-ß-induced epithelial-to-mesenchymal transition in ovarian cancer.

Background: Ovarian cancer (OC) is the second most common gynecological malignancy and has a high mortality rate. The current chemotherapeutic drugs have the disadvantages of drug resistance and side effects. Myricetin, a kind of natural compound, has the advantages of easy extraction, low price, and fewer side effects. Multiple studies have demonstrated the anti-cancer properties of myricetin. However, its impact on OC is still unknown and needs further investigation. Therefore, this study aimed to elucidate the mechanism by which myricetin suppresses transforming growth factor-ß (TGF-ß) -induced epithelial-to-mesenchymal transition (EMT) in OC through in vivo and in vitro experiments. Methods: In vitro experiments were conducted to evaluate the effects of myricetin on cell proliferation and apoptosis using CCK8 assay, plate clonal formation assay, and flow cytometry. Western blot was employed to evaluate the expression levels of caspase-3, PARP, and the MAPK/ERK and PI3K/AKT signaling pathways. Wound healing, transwell, western blot and immunofluorescence assay were used to detect TGF-ß-induced cell migration, invasion, EMT and the levels of Smad3, MAPK/ERK, PI3K/AKT signaling pathways. Additionally, a mouse xenograft model was established to verify the effects of myricetin on OC in vivo. Results: Myricetin inhibited OC proliferation through MAPK/ERK and PI3K/AKT signaling pathways. Flow cytometry and western blot analyses demonstrated that myricetin promoted apoptosis by increasing the expression of cleaved-PARP and cleaved-caspase-3 and the ratio of Bax/Bcl-2 in OC. Furthermore, myricetin suppressed the TGF-ß-induced migration and invasion by transwell and wound healing assays. Mechanistically, western blot indicated that myricetin reversed TGF-ß-induced metastasis through Smad3, MAPK/ERK and PI3K/AKT signaling pathway. In vivo, myricetin significantly repressed OC progression and liver and lung metastasis. Conclusion: Myricetin exhibited inhibitory effects on OC progression and metastasis both in vivo and in vitro. And it also reversed TGF-ß-induced EMT through the classical and non-classical Smad signaling pathways.

Focus on the performance enhancement of micro/nanomotor-based biosensors.

Micro/nanomotors (MNMs) emerge as a vital candidate for biosensing due to its nano-size structure, high surface-to-area ratio, directional mobility, biocompatibility, and ease of functionalization, therefore being able to detect objects with high efficiency, precision, and selectivity. The driving mode, nanostructure, materials property, preparation technique, and biosensing applications have been thoroughly discussed in publications. To promote the MNMs-based biosensors from in vitro to in vivo, it is necessary to give a comprehensive discussion from the perspective of sensing performances enhancement. However, until now, there is few reviews dedicated to the systematic discussion on the multiple performance enhancement schemes and the current challenges of MNMs-based biosensors. Bearing it in mind and based on our research experience in this field, we summarized the enhancement methods for biosensing properties such as sensitivity, selectivity, detection time, biocompatibility, simplify system operation, and environmental availability. We hope that this review provides the readers with fundamental understanding on performance enhancement schemes for MNMs-based biosensors.

Effectiveness of Acupuncture for Prophylactic Treatment of Migraine: A Systematic Review and Bayesian Network Meta-Analysis.

It is aimed to evaluate the effectiveness and provide evidence-based medical support for acupuncture as a prophylactic treatment for migraines. Randomized controlled trials (RCTs) from inception to April 2022 are included in 14 databases. Pairwise meta-analysis is conducted using STATA software V14.0, while Windows Bayesian Inference Using Gibbs Sampling (WinBUGS V.1.4.3) is applied to generate Bayesian Network Meta-analysis (NMA) using Markov chain Monte Carlo algorithm. Forty RCTs are included, with 4405 participants. The effectiveness of six acupuncture techniques, three types of prophylactic drugs, and psychotherapy are compared and ranked. Acupuncture outperformed prophylactic drugs in terms of diminishing visual analog scale (VAS) score, migraine attack frequency, and days during the treatment and at the 12-week follow-up. At the 12-week follow-up, the effectiveness of various interventions is ranked as follows: manual acupuncture (MA) > electroacupuncture (EA) > calcium antagonists (CA) in reducing VAS score; MA > EA > CA in reducing migraine attack frequency; MA > EA > ß-receptor blocker and CA in reducing headache attack days. Acupuncture is a promising treatment for migraine prevention. The best option of acupuncture for improving various migraine outcomes has changed over time. However, the quality of included trials and NMA inconsistency limited the credibility of the conclusion.

Depletion of stearoyl-CoA desaturase (scd) leads to fatty liver disease and defective mating behavior in zebrafish.

Stearyl coenzyme A desaturase (SCD), also known as delta-9 desaturase, catalyzes the rate-limiting step in the formation of monounsaturated fatty acids. In mammals, depletion or inhibition of SCD activity generally leads to a decrease in triglycerides and cholesteryl esters. However, the endogenous role of scd in teleost fish remains unknown. Here, we generated a zebrafish scd mutant (scd-/-) to elucidate the role of scd in lipid metabolism and sexual development. Gas chromatography-mass spectrometry (GC-MS) showed that the scd-/- mutants had increased levels of saturated fatty acids C16:0 and C18:0, and decreased levels of monounsaturated fatty acids C16:1 and C18:1. The mutant fish displayed a short stature and an enlarged abdomen during development. Unlike Scd-/- mammals, the scd-/- zebrafish showed significantly increased fat accumulation in the whole body, especially in the liver, leading to hepatic mitochondrial dysfunction and severe cell apoptosis. Mechanistically, srebf1, a gene encoding a transcriptional activator related to adipogenesis, acc1 and acaca, genes involved in fatty acid synthesis, and dgat2, a key gene involved in triglyceride synthesis, were significantly upregulated in mutant livers to activate fatty acid biosynthesis and adipogenesis. The scd-/- males exhibited defective natural mating behavior due to defective genital papillae but possessed functional mature sperm. All defects in the scd-/- mutants could be rescued by ubiquitous transgenic overexpression of scd. In conclusion, our study demonstrates that scd is indispensable for maintaining lipid homeostasis and development of secondary sexual characteristics in zebrafish.

Motion detection and direction recognition in a photonic spiking neural network consisting of VCSELs-SA.

Motion detection and direction recognition are two important fundamental visual functions among the many cognitive functions performed by the human visual system. The retina and visual cortex are indispensable for composing the visual nervous system. The retina is responsible for transmitting electrical signals converted from light signals to the visual cortex of the brain. We propose a photonic spiking neural network (SNN) based on vertical-cavity surface-emitting lasers with an embedding saturable absorber (VCSELs-SA) with temporal integration effects, and demonstrate that the motion detection and direction recognition tasks can be solved by mimicking the visual nervous system. Simulation results reveal that the proposed photonic SNN with a modified supervised algorithm combining the tempotron and the STDP rule can correctly detect the motion and recognize the direction angles, and is robust to time jitter and the current difference between VCSEL-SAs. The proposed approach adopts a low-power photonic neuromorphic system for real-time information processing, which provides theoretical support for the large-scale application of hardware photonic SNN in the future.

Ability of Spalangia endius (Hymenoptera: Pteromalidae) to Parasitize Bactrocera dorsalis (Diptera: Tephritidae) after Switching Hosts.

We studied the parasitism capacity of Spalangia endius as a pupal parasite of Bactocera dorsalis after switching hosts. We used pupae of B. dorsalis and M. domestica as the hosts and studied parasitism by S. endius in the laboratory. The parasitism capacities were compared at different host densities and different parasitoid ages. The two functional responses of S. endius fitted a Holling Type II equation. More M. domestica were parasitized than B. dorsalis at all the densities. The ability of S. endius to control M. domestica was α/Th (parasitism capacity) = 32.1950, which was much stronger than that of control B. dorsalis, which was α/Th = 4.7380. The parasitism rate of wasps that had parasitized B. dorsalis had decreased by the emergence time of parasitoids. These results suggest that the parasitoid-pest ratio should be 1:25 to maintain a relatively stable parasitism rate for control of B. dorsalis. The S. endius colony reared on M. domestica successfully controlled a low-density population of B. dorsalis in the lab. We provide evidence suggesting that the parasitism capacity of S. endius needs to be improved.

Behavioral response of Panonychus citri (McGregor) (Acari: Tetranychidae) to synthetic chemicals and oils.

BACKGROUND: Panonychus citri (McGregor) (Acari: Tetranychidae) population outbreaks after the citrus plantation's chemical application is a common observation. Dispersal behavior is an essential tool to understand the secondary outbreak of P. citri population. Therefore, in the current study, the dispersal activity of P. citri was observed on the leaf surfaces of Citrus reticulata (Rutaceae) treated with SYP-9625, abamectin, vegetable oil, and EnSpray 99. METHOD: Mites were released on the first (apex) leaf of the plant (adaxial surface) and data were recorded after 24 h. The treated, untreated, and half-treated data were analyzed by combining the leaf surfaces (adaxial right, adaxial left, abaxial right, and abaxial left). All experiments were performed in open-air environmental conditions. RESULTS: The maximum number of mites was captured on the un-treated or half-treated surfaces due to chemicals repellency. Chemical bioassays of the free-choice test showed that all treatments significantly increased the mortality of P. citri depending on application method and concentration. A significant number of mites repelled away from treated surfaces and within treated surfaces except adaxial left and abaxial right surfaces at LC30. In the no-choice test, SYP-9625 gave maximum mortality and dispersal by oils than others. No significant differences were observed within the adaxial and abaxial except abaxial surface at LC30. Therefore, the presence of tested acaricides interferes with P. citri dispersal within leaf surfaces of plantations depending on the mites released point and a preferred site for feeding.

Intervention for reducing anxiety during screening mammography: A protocol for systematic review and meta-analysis.

BACKGROUND: Mammography is considered a fundamental part of diagnosis in modern health care services. It provides low dose images of normal structures and pathological soft tissues in the breast. Many reports suggested that intervention is playing a positive role in anxiety related to mammography, but there is no high-quality evidence to prove its effects. This paper reports the protocol of a systematic review (SR) and meta-analysis (MA) to clarify effectiveness of intervention during screening mammography. METHODS: A systematic literature search will be performed in the Cochrane Library, PubMed, Embase and Web of Science from inception to July 2020. Randomized controlled trials (RCTs) will be included to evaluate any interventions in the treatment of anxiety related to mammography screening. The main outcome measure is the impact on patient anxiety, and the impact on patient breast cancer worry, the impact on patient satisfaction are the additional outcome measure. Risk of bias assessment of the included RCTs will be carried out using Cochrane Collaboration's tool for RCTs. The Review Manager 5.4 for Windows will be used to perform the MA and generate the result figures. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) will be used to evaluate the quality of evidence. Subgroup analysis and sensitivity analysis will be conducted to assess the robustness of the results. RESULTS: A total of 782 English studies of anxiety related to mammography screening were obtained through search. After preliminary screening, 773 non-conforming studies were excluded. Finally, nine English studies of anxiety related to mammography screening will be included for full-text assessment. We will submit the results of this SR and MA to a peer-reviewed journal for publication. CONCLUSIONS: This study will provide reliable evidence for intervention for reducing anxiety in women receiving screening mammography. INPLASY REGISTRATION NUMBER: INPLASY202070131.

Photonic spiking neural network based on excitable VCSELs-SA for sound azimuth detection.

We propose a photonic spiking neural network (SNN) based on excitable vertical-cavity surface-emitting lasers with an embedded saturable absorber (VCSELs-SA) for emulating the sound azimuth detection function of the brain for the first time. Here, the spike encoding and response properties based on the excitability of VCSELs-SA are employed, and the difference between spike timings of two postsynaptic neurons serves as an indication of sound azimuth. Furthermore, the weight matrix contributing to the successful sound azimuth detection is carefully identified, and the effect of the time interval between two presynaptic spikes is considered. It is found that the weight range that can achieve sound azimuth detection decreases gradually with the increase of the time interval between the sound arriving at the left and right ears. Besides, the effective detection range of the time interval between two presynaptic spikes is also identified, which is similar to that of the biological auditory system, but with a much higher resolution which is at the nanosecond time scale. We further discuss the effect of device variations on the photonic sound azimuth detection. Hence, this photonic SNN is biologically plausible, which has comparable low energy consumption and higher resolution compared with the biological system. This work is valuable for brain-inspired information processing and a promising foundation for more complex spiking information processing implemented by photonic neuromorphic computing systems.

Transcriptome characterization and gene expression analysis related to chemoreception in Trichogramma chilonis, an egg parasitoid.

Chemoreception is critical for the survival of insects. Insects have a variety of behavioral responses, such as mating, host searching and ovipositing, in response to different odor signals detected in their living environment. Trichogramma chilonis, an egg parasitoid, acts as an efficient and effective biocontrol reagent for many agricultural and forestry insect pests in many parts of China. However, little is known about the molecular mechanism of the olfaction-evoked behavior in T. chilonis. In the present study, we conducted transcriptome profiling analysis of T. chilonis based on the Illumina high-throughput sequencing platform in order to explore differences of chemoreception between male and female T. chilonis. In this study, a total of 85 chemosensory genes were identified from transcriptomic data, including 45 odorant receptors (ORs), 22 odorant binding proteins (OBPs), 14 ionotropic receptors (IRs), 2 sensory neuron membrane proteins (SNMPs) and 2 chemosensory proteins (CSPs). From the analysis of the transcriptome, most of the candidate olfactory genes had similar expression levels in males and females, including a few OR and OBP genes (TchiOR38, TchiOR39, TchiOR40, TchiOR41, TchiOR42, TchiOR43, TchiOR44, TchiOR45, TchiOBP1, TchiOBP4, TchiOBP10, TchiOBP12, TchiOBP18 and TchiOBP19) which showed male-biased expression. Some annotated unigenes were chosen randomly to have qRT-PCR, which verified the correctness of analysis of transcriptome in T. chilonis. This is the first study to obtain and identify candidate genes related to chemoreception in T. chilonis. Our work lays a solid foundation for related future research on the chemosensory system of T. chilonis at the molecular level and helps advance the use of T. chilonis as biological control agents.