Clinical practice guideline for acupuncture and moxibustion: Allergic rhinitis.

Acupuncture is one of the most effective complementary therapies for allergic rhinitis (AR) and has been recommended by several clinical practice guidelines (CPGs) for AR. However, these CPGs mentioned acupuncture without making recommendations for clinical implementation and therapeutic protocols, therefore limiting the applicability of acupuncture therapies for AR. Hence, for the benefit of acupuncture practitioners around the world, the World Federation of Acupuncture-moxibustion Societies have initiated a project to develop the CPG for the use of acupuncture and moxibustion to treat AR. This CPG was developed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, referring to the principles of the World Health Organization Handbook for Guideline Development. During the development of the CPG, the guideline development group (GDG) played an important role. The clinical questions, recommendations and therapeutic protocols were all formulated by the GDG using the modified Delphi method. The CPG contains recommendations for 15 clinical questions about the use of acupuncture and moxibustion interventions. These include one strong recommendation for the intervention based on high-quality evidence, three conditional recommendations for either the intervention or standard care, and 11 conditional recommendations for the intervention based on very low quality of evidence. The CPG also provides one filiform needle acupuncture protocol and five moxibustion protocols extracted based on the protocols presented in randomized controlled trials reviewed by the GDG. Please cite this article as: Du SH, Chen S, Wang SZ, Wang GQ, Du S, Guo W, Xie XL, Peng BH, Yang C, Zhao JP. Clinical practice guideline for acupuncture and moxibustion: Allergic rhinitis. J Integr Med. 2024; Epub ahead of print.

Cnidii Fructus: A traditional Chinese medicine herb and source of antiosteoporotic drugs.

BACKGROUND: Osteoporosis (OP) is a prevalent chronic metabolic bone disease for which limited countermeasures are available. Cnidii Fructus (CF), primarily derived from Cnidium monnieri (L.) Cusson., has been tested in clinical trials of traditional Chinese medicine for the management of OP. Accumulating preclinical studies indicate that CF may be used against OP. MATERIALS AND METHODS: Comprehensive documentation and analysis were conducted to retrieve CF studies related to its main phytochemical components as well as its pharmacokinetics, safety and pharmacological properties. We also retrieved information on the mode of action of CF and, in particular, preclinical and clinical studies related to bone remodeling. This search was performed from the inception of databases up to the end of 2022 and included PubMed, China National Knowledge Infrastructure, the National Science and Technology Library, the China Science and Technology Journal Database, Weipu, Wanfang, the Web of Science and the China National Patent Database. RESULTS: CF contains a wide range of natural active compounds, including osthole, bergapten, imperatorin and xanthotoxin, which may underlie its beneficial effects on improving bone metabolism and quality. CF action appears to be mediated via multiple processes, including the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK), Wnt/ß-catenin and bone morphogenetic protein (BMP)/Smad signaling pathways. CONCLUSION: CF and its ingredients may provide novel compounds for developing anti-OP drugs.

Vitamin D delays intervertebral disc degeneration and improves bone quality in ovariectomized rats.

Known to be involved in bone-cartilage metabolism, Vitamin D (VD) may play a role in human's disc pathophysiology. Given that postmenopausal women are prone to suffer VD deficiency and intervertebral disc degeneration (IDD), this study is intended to investigate whether VD can delay IDD in ovariectomized rats by improving bone microstructure and antioxidant stress. Female Sprague-Dawley rats were randomly allocated into four groups: sham, oophorectomy (OVX)+VD deficiency (VDD), OVX, and OVX+VD supplementation (VDS). In vivo, after a 6-month intervention, imaging and pathology slice examinations showed that IDD induced by OVX was significantly alleviated in VDS and deteriorated by VDD. The expressions of aggrecan and Collagen II in intervertebral disc were reduced by OVX and VDD, and elevated by VDS. Compared with the OVX+VDD and OVX group vertebrae, OVX+VDS group vertebrae showed significantly improved endplate porosity and lumbar bone mineral density with increased percent bone volume and trabecular thickness. Furthermore, 1α,25(OH)2D3 restored the redox balance (total antioxidant capacity, ratio of oxidized glutathione/glutathione) in the disc. The cocultivation of 1α,25(OH)2D3 and nucleus pulposus cells (NPCs) was conducted to observe its potential ability to resist excessive oxidative stress damage induced by H2O2. In vitro experiments revealed that 1α,25(OH)2D3 reduced the senescence, apoptosis, and extracellular matrix degradation induced by H2O2 in NPCs. In conclusion, VDS exhibits protective effects in OVX-induced IDD, partly by regulating the redox balance and preserving the microstructure of endplate. This finding provides a new idea for the prevention and treatment of IDD.

Correlation between Anxiety, Depression, and Intestinal Flora in Breast Cancer Patients: Based on 16S rRNA Sequence Analysis.

Objective: To explore intestinal flora differences in species diversity, community structure, and abundance of breast cancer and non-breast cancer populations with anxiety and depression and the corresponding group without anxiety and depression by 16S rRNA high-throughput sequencing technology. Method: Breast cancer and non-breast cancer participants were recruited based on the inclusion and exclusion criteria as the research subjects. The study employed the anxiety self-assessment scale and the depression self-rating scale in the questionnaire survey to collect data. Results: The scores of anxiety and depression of the four groups are as follows: In the breast cancer with anxiety and/or depression (BCAD) group, the anxiety score is 58.80 ± 5.27 and the depression score is 59.60 ± 4.94. In the breast cancer without anxiety and/or depression (BCWAD) group, the anxiety score is 36.53 ± 4.52 and the depression score is 38.20 ± 3.78. In the non-breast cancer group with anxiety and/or depression (HAD) group, the anxiety score is 57.87 ± 4.53 and the depression score is 59.13 ± 5.24. In the non-breast cancer group without anxiety and depression (HWAD) group, the anxiety score is 35.13 ± 5.28 and the depression score is 32.33 ± 4.37. Conclusion: The intestinal flora of the breast cancer patients is significantly different from those of non-breast cancer patients, suggesting that there is an internal relationship between the changes in the intestinal flora and the occurrence and development of breast cancer. People with anxiety and depression without breast cancer show changes in their intestinal flora, suggesting that the changes of the intestinal flora can indeed trigger anxiety and depression. For the breast cancer patients with anxiety and depression, the intestinal flora shows a decrease in diversity and abundance, suggesting that the intestinal flora of the breast cancer patients with anxiety and depression undergo further changes. Thus the intestinal flora can become a new tool for monitoring, preventing, and treating the breast cancer and negative emotions.

α-Ketoglutaric acid ameliorates intervertebral disk degeneration by blocking the IL-6/JAK2/STAT3 pathway.

Intervertebral disk degeneration (IVDD) is the major cause of low back pain. Alpha-ketoglutaric acid (α-KG), an important intermediate in energy metabolism, has various functions, including epigenetic regulation, maintenance of redox homeostasis, and antiaging, but whether it can ameliorate IVDD has not been reported. Here, we examined the impacts of long-term administration of α-KG on aging-associated IVDD in adult rats. In vivo and in vitro experiments showed that α-KG supplementation effectively ameliorated IVDD in rats and the senescence of nucleus pulposus cells (NPCs). α-KG supplementation significantly attenuated senescence, apoptosis, and matrix metalloproteinase-13 (MMP-13) protein expression, and it increased the synthesis of aggrecan and collagen II in IL-1ß-treated NPCs. In addition, α-KG supplementation reduced the levels of IL-6, phosphorylated JAK2 and STAT3, and the nuclear translocation of p-STAT3 in IL-1ß-induced degenerating NPCs. The effects of α-KG were enhanced by AG490 in NPCs. The underlying mechanism may involve the inhibition of JAK2/STAT3 phosphorylation and the reduction of IL-6 expression. Our findings may help in the development of new therapeutic strategies for IVDD.NEW & NOTEWORTHY Alpha-ketoglutaric acid (α-KG) exerted its protective effect on nucleus pulposus cells' (NPCs) degeneration by inhibiting the senescence-associated secretory phenotype and extracellular matrix degradation. The possible mechanism may be associated with negatively regulating the JAK2/STAT3 phosphorylation and the decreased IL-6 expression, which could be explained by a blockage of the positive feedback control loop between IL-6 and JAK2/STAT3 pathway.

[Dong's extraordinary point needling technique combined with medication for postoperative complications of anal fistula: a randomized controlled trial].

OBJECTIVE: To observe the effect of Dong's extraordinary point needling technique on postoperative complications of anal fistula. METHODS: A total of 241 patients undergoing anal fistula surgery were randomly divided into an observation group (121 cases, 3 cases dropped off) and a control group (120 cases, 2 cases dropped off). The patients in the control group were treated with intramuscular injection of compound diclofenac sodium injection and oral administration of tamsulosin hydrochloride sustained release capsules. In addition to the treatment in the control group, the patients in the observation group were treated with Daoma needling technique at the "Sanqi points" (Qimen point, Qijiao point, and Qizheng point) combined with Dongqi needling technique at "Sanhuang points" (sub-Tianhuang point, Dihuang point, Renhuang point), with each session lasting 30 min. The treatment in the two groups both started on the first day after surgery, and was given once daily for 14 consecutive days. Visual analog scale (VAS) score was compared between the two groups on postoperative day 1, 7, and 14; bladder residual urine volume, spontaneous voiding volume, and urinary catheterization frequency were assessed after treatment on postoperative day 1; and anorectal dynamic indexes (anal canal resting pressure, rectal resting pressure, maximum squeeze pressure of the anal canal, and minimum rectal sensory threshold) were evaluated before surgery and on postoperative day 4. Clinical efficacy was assessed in both groups one month after surgery. RESULTS: On postoperative day 7 and 14, the VAS scores of both groups were lower than those on postoperative day 1 (P<0.05), and the VAS scores in the observation group were lower than those in the control group (P<0.05). The bladder residual urine volume and urinary catheterization frequency in the observation group were lower than those in the control group (P<0.05), while the spontaneous voiding volume was higher than that in the control group (P<0.05). On postoperative day 4, the anal canal resting pressure, maximum squeeze pressure of the anal canal, and the minimum rectal sensory threshold were lower than preoperative values (P<0.05), while the rectal resting pressure was higher than preoperative value (P<0.05) in both groups. The anal canal resting pressure, maximum squeeze pressure of the anal canal, and minimum rectal sensory threshold were lower than those in the control group, and the rectal resting pressure was higher than that in the control group (P<0.05). The effective rate was 93.2% (110/118) in the observation group, which was higher than 84.7% (100/118) in the control group (P<0.05). CONCLUSION: Dong's extraordinary point needling technique could reduce postoperative pain, alleviate urinary retention, and improve defecation in patients undergoing anal fistula surgery.

First principal observation documenting the three-dimensional uptake of cadmium and spatial distribution of cadmium hydroxyapatite mineral in bone char.

The 3-D matrix scale ion-exchange mechanism was explored for high-capacity cadmium (Cd) removal using bone chars (BC) chunks (1-2 mm) made at 500 °C (500BC) and 700 °C (700BC) in aqueous solutions. The Cd incorporation into the carbonated hydroxyapatite (CHAp) mineral of BC was examined using a set of synchrotron-based techniques. The Cd removal from solution and incorporation into mineral lattice were higher in 500BC than 700BC, and the diffusion depth was modulated by the initial Cd concentration and charring temperature. A higher carbonate level of BC, more pre-leached Ca sites, and external phosphorus input enhanced Cd removal. The 500BC showed a higher CO32-/PO43- ratio and specific surface area (SSA) than the 700BC, providing more vacant sites by dissolution of Ca2+. In situ observations revealed the refilling of sub-micron pore space in the mineral matrix because of Cd incorporation.The X-ray nanodiffraction (XND) analyses revealed that Cd was mainly removed from water by incorporation into the mineral lattice of 500BC via ion exchange, rather than surface sorption and precipitation, and the mineral phase was transformed from hydroxyapatite (HAp) to cadmium hydroxyapatite (Cd-HAp). The Rietveld's refinement of X-ray diffraction (XRD) data resolved up to 91% of the crystal displacement of Ca2+ by Cd2+. The specific phase and stoichiometry of the new Cd-HAp mineral was dependent on the level of ion exchange. This mechanistic study confirmed that 3-D ion exchange was the most important path for heavy metal removal from aqueous solution and immobilization in BC mineral matrix, and put forward a novel and sustainable remediation strategy for Cd removal in wastewater and soil clean-up.

Targeting Ferroptosis in Cancer by Natural Products: An Updated Review.

Ferroptosis is a new cell death process characterized by massive iron accumulation and lipid peroxidation. Emerging evidence demonstrates that ferroptosis plays a crucial role in the development and progression of tumorigenesis. Targeting it is a potentially effective cancer prevention and treatment strategy in the clinic. A comprehensive review of molecular mechanisms of targeting ferroptosis in cancer by natural products needs to be re-summarized and updated due to the advances in research. We searched and reviewed relevant literature through the database Web of Science, mainly focusing on the regulatory effects of natural products and their active compounds in treating or preventing cancer by regulating ferroptosis. A total of 62 kinds of natural products and their active compounds were reported to exert antitumor effects via causing ferroptosis of cancer cells by regulating the System Xc--GPX4 axis and lipid, mitochondrial, and iron metabolism. Natural products have advantages in improving chemotherapy's therapeutic effects by causing cancer cell ferroptosis through their polypharmacological actions. These molecular mechanisms of ferroptosis regulation by natural products will pave the way for developing natural antitumor drugs based on regulating ferroptosis.

Genome-Wide Identification and Analysis Uncovers the Potential Role of JAZ and MYC Families in Potato under Abiotic Stress.

As key regulators of the Jasmonates (JAs) signal transduction pathway, JAZ protein, and MYC transcription factors are imperative for plant response to external environmental changes, growth, and development. In this study, 18 StJAZs and 12 StMYCs were identified in potatoes. Their chromosomal position, phylogenetic development, gene structure, and promoter cis-acting parts of the StJAZ genes were analyzed. In addition, Protein-Protein Interaction (PPI) network analysis of StJAZ and StMYC gene families and yeast two-hybrid assay demonstrated that five StMYCs can interact with 16 StJAZs, which provides new insights into the operation mechanism of StJAZs and StMYCs in JA signal response. Moreover, we explored the expression profiles of StJAZs and StMYCs genes in different tissues and during abiotic stresses by RNA-seq data. Based on the PPI network and transcriptome data, the genes StJAZ11, StJAZ16, and StMYC6 were chosen for further qRT-PCR study under salt or mannitol treatment. Under mannitol-induced drought or salinity treatment, the expression patterns of StMYC6, StJAZ11, and StJAZ16 were different, indicating that the JAZ protein and MYC transcription factor may be engaged in the response of potatoes to abiotic stress, which opened up a new research direction for the genetic improvement of potatoes in response to environmental stress.

[Bombyx Batryticatus extract promotes microglia polarization to improve neuron injury and behaviors of cerebral ischemia/reperfusion rats].

This study aims to investigate the effect of Bombyx Batryticatus extract(BBE) on behaviors of rats with global cerebral ischemia reperfusion(I/R) and the underlying mechanism. The automatic coagulometer was used to detect the four indices of human plasma coagulation after BBE intervention for quality control of the extract. Sixty 4-week-old male SD rats were randomized into sham operation group(equivalent volume of normal saline, ip), model group(equivalent volume of normal saline, ip), positive drug group(900 IU·kg~(-1) heparin, ip), and low-, medium-, and high-dose BBE groups(0.45, 0.9, and 1.8 mg·g~(-1)·d~(-1) BBE, ip). Except the sham operation group, rats were subjected to bilateral common carotid artery occlusion followed by reperfusion(BCCAO/R) to induce I/R. The administration lasted 7 days for all the groups. The behaviors of rats were examined by beam balance test(BBT). Morphological changes of brain tissue were observed based on hematoxylin-eosin(HE) staining. Immunofluorescence method was used to detect common leukocyte antigen(CD45), leukocyte differentiation antigen(CD11b), and arginase-1(Arg-1) in cerebral cortex(CC). The protein expression of interleukin-1ß(IL-1ß), interleukin-4(IL-4), interleukin-6(IL-6), and interleukin-10(IL-10) was detected by enzyme-linked immunosorbent assay(ELISA). The non-targeted metabonomics was employed to detect the levels of metabolites in plasma and CC of rats after BBE intervention. The results of quality control showed that the BBE prolonged the activated partial thromboplastin time(APTT), prothrombin time(PT), and thrombin time(TT) of human plasma, which was similar to the anticoagulation effect of BBE obtained previously. The results of behavioral test showed that the BBT score of the model group increased compared with that of the sham operation group. Compared with the model group, BBE reduced the BBT score. As for the histomorphological examination, compared with the sham operation group, the model group showed morphological changes of a lot of nerve cells in CC. The nerve cells with abnormal morphology in CC decreased after the intervention of BBE compared with those in the model group. Compared with the sham operation group, the model group had high average fluorescence intensity of CD45 and CD11b in the CC. The average fluorescence intensity of CD11b decreased and the average fluorescence intensity of Arg-1 increased in CC in the low-dose BBE group compared with those in the model group. The average fluorescence intensity of CD45 and CD11b decreased and the average fluorescence intensity of Arg-1 increased in medium-and high-dose BBE groups compared with those in the model group. The expression of IL-1ß and IL-6 was higher and the expression of IL-4 and IL-10 was lower in the model group than in the sham operation group. The expression of IL-1ß and IL-6 was lower and the expression of IL-4 and IL-10 was higher in the low-dose, medium-dose, and high-dose BBE groups than in the model group. The results of non-targeted metabonomics showed that 809 metabolites of BBE were identified, and 57 new metabolites in rat plasma and 45 new metabolites in rat CC were found. BBE with anticoagulant effect can improve the behaviors of I/R rats, and the mechanism is that it promotes the polarization of microglia to M2 type, enhances its anti-inflammatory and phagocytic functions, and thus alleviates the damage of nerve cells in CC.

[From the body-mind holism to psychosomatic medicine: theory and practice of acupuncture and moxibustion].

The traditional life concept of "body-mind holism" in Chinese medicine has drawn a special attention with the development of modern psychosomatic medicine. The "body-mind holism" is valuable in the guidance for clinical acupuncture practice, but, it is only remained on the theoretical significance by the medical masters in the past dynasties. In the paper, based on the understanding of Huangdi Neijing (Yellow Emperor's Internal Classic), the similarities and differences are compared between the body-mind theory and psychosomatic medicine. In association with clinical observation, from three aspects, i.e. body-mind pathogenesis, acupoint detection and observing the mind, and body-mind treatment, the guidance of "body-mind holism" is explored for the clinical diagnosis and treatment of acupuncture and moxibustion; the referents of "body" and "mind" are clarified in views of disease, diagnosis and treatment; and the treatment strategies of acupuncture and moxibustion are discussed in the perspective of "body-mind holism".

Simiao San alleviates hyperuricemia and kidney inflammation by inhibiting NLRP3 inflammasome and JAK2/STAT3 signaling in hyperuricemia mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Simiao San (SmS), a famous traditional Chinese formula, is clinically used to treat patients with hyperuricemia (HUA). However, its mechanism of action on lowering uric acid (UA) and inhibiting inflammation still deserves further investigation. AIM OF THE STUDY: To examine the effect and its possible underlying mechanism of SmS on UA metabolism and kidney injury in HUA mouse. MATERIALS AND METHODS: The HUA mouse model was constructed with the combined administration of both potassium oxalate and hypoxanthine. The effects of SmS on UA, xanthine oxidase (XOD), creatinine (CRE), blood urea nitrogen (BUN), interleukin-10 (IL-10), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by ELISA or biochemical assays. Hematoxylin and eosin (H&E) was used to observe pathological alterations in the kidneys of HUA mice. The expression levels of organic anion transporter 1 (OAT1), recombinant urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), nucleotide binding domain and leucine rich repeat pyrin domain containing 3 (NLRP3), Cleaved-Caspase 1, apoptosis-associated speck like protein (ASC), nuclear factor kappa-B (NF-κB), IL-6, janus kinase 2 (JAK2), phosphor (P)-JAK2, signal transducers and activators of transcription 3 (STAT3), P-STAT3, suppressor of cytokine signaling 3 (SOCS3) were examined by Western blot and/or immunohistochemical (IHC) staining. The major ingredients in SmS were identified by a HPLC-MS assay. RESULTS: HUA mouse exhibited an elevation in serum levels of UA, BUN, CRE, XOD, and the ratio of urinary albumin to creatinine (UACR), and a decline in urine levels of UA and CRE. In addition, HUA induces pro-inflammatory microenvironment in mouse, including an increase in serum levels of IL-1ß, IL-6, and TNF-α, and renal expressions of URAT1, GULT9, NLRP3, ASC, Cleaved-Caspase1, P-JAK2/JAK2, P-STAT3/STAT3, and SOCS3, and a decrease in serum IL-10 level and renal OAT1 expression as well as a disorganization of kidney pathological microstructure. In contrast, SmS intervention reversed these alterations in HUA mouse. CONCLUSION: SmS could alleviate hyperuricemia and renal inflammation in HUA mouse. The action mechanisms behind these alterations may be associated with a limitation of the NLRP3 inflammasome and JAK2/STAT3 signaling pathways.

Observation of anti-damping spin-orbit torques generated by in-plane and out-of-plane spin polarizations in MnPd3.

Large spin-orbit torques (SOTs) generated by topological materials and heavy metals interfaced with ferromagnets are promising for next-generation magnetic memory and logic devices. SOTs generated from y spin originating from spin Hall and Edelstein effects can realize field-free magnetization switching only when the magnetization and spin are collinear. Here we circumvent the above limitation by utilizing unconventional spins generated in a MnPd3 thin film grown on an oxidized silicon substrate. We observe conventional SOT due to y spin, and out-of-plane and in-plane anti-damping-like torques originated from z spin and x spin, respectively, in MnPd3/CoFeB heterostructures. Notably, we have demonstrated complete field-free switching of perpendicular cobalt via out-of-plane anti-damping-like SOT. Density functional theory calculations show that the observed unconventional torques are due to the low symmetry of the (114)-oriented MnPd3 films. Altogether our results provide a path toward realization of a practical spin channel in ultrafast magnetic memory and logic devices.

Antimicrobial activity and comparative metabolomic analysis of Priestia megaterium strains derived from potato and dendrobium.

The growth of endophytic bacteria is influenced by the host plants and their secondary metabolites and activities. In this study, P. megaterium P-NA14 and P. megaterium D-HT207 were isolated from potato tuber and dendrobium stem respectively. They were both identified as Priestia megaterium. The antimicrobial activities and metabolites of both strains were explored. For antimicrobial activities, results showed that P. megaterium P-NA14 exhibited a stronger inhibition effect on the pathogen of dendrobium, while P. megaterium D-HT207 exhibited a stronger inhibition effect on the pathogen of potato. The supernatant of P. megaterium P-NA14 showed an inhibition effect only on Staphylococcus aureus, while the sediment of P. megaterium D-HT207 showed an inhibition effect only on Escherichia coli. For metabolomic analysis, the content of L-phenylalanine in P. megaterium P-NA14 was higher than that of P. megaterium D-HT207, and several key downstream metabolites of L-phenylalanine were associated with inhibition of S. aureus including tyrosine, capsaicin, etc. Therefore, we speculated that the different antimicrobial activities between P. megaterium P-NA14 and P. megaterium D-HT207 were possibly related to the content of L-phenylalanine and its metabolites. This study preliminarily explored why the same strains isolated from different hosts exhibit different activities from the perspective of metabolomics.

Point-of-Care Testing of Enzyme Polymorphisms for Predicting Hypnotizability and Postoperative Pain.

Hypnotizability is a stable trait that moderates the benefit of hypnosis for treating pain, but limited availability of hypnotizability testing deters widespread use of hypnosis. Inexpensive genotyping of four single-nucleotide polymorphisms in the catechol-o-methyltransferase (COMT) gene was performed using giant magnetoresistive biosensors to determine if hypnotizable individuals can be identified for targeted hypnosis referrals. For individuals with the proposed optimal COMT diplotypes, 89.5% score highly on the Hypnotic Induction Profile (odds ratio, 6.12; 95% CI, 1.26-28.75), which identified 40.5% of the treatable population. Mean hypnotizability scores of the optimal group were significantly higher than the total population (P = 0.015; effect size = 0.60), an effect that was present in women (P = 0.0015; effect size = 0.83), but not in men (P = 0.28). In an exploratory cohort, optimal individuals also reported significantly higher postoperative pain scores (P = 0.00030; effect size = 1.93), indicating a greater need for treatment.

Genetically predicted selenium concentrations and thyroid function: A two-sample Mendelian randomization study.

OBJECTIVE: The impact of selenium (Se) on human thyroid function remains unclear, with inconsistent results from recent epidemiological studies. Moreover, the observed associations are prone to bias due to potential confounding and reverse causation. Mendelian randomization (MR) analysis facilitates the large minimization of biases produced by environmental and lifestyle influences, providing unconfounded estimates of causal effects using instrumental variables. We aim to examine the association between Se concentrations and human thyroid function using a two-sample MR analysis. DESIGN AND METHODS: Genetic instruments for Se concentrations, including toenail and blood (TAB) and blood Se concentrations, were identified from a genome-wide association study (GWAS) of blood Se (n = 5477) and toenail Se levels (n = 4162). GWAS summary statistics on thyroid phenotypes were downloaded from the ThyroidOmics consortium, including thyroid-stimulating hormone (TSH) (n = 54,288), free thyroxin (FT4) (n = 49,269), hypo (n = 53,423), and hyperthyroidism (n = 51,823). The MR study was conducted using the inverse-variance weighted (IVW) method, supplemented with the weighted median and the mode-based method. RESULTS: Genetically determined TAB Se was negatively associated with FT4 (ß = -.067; 95% confidence interval [CI] = -0.106, -0.028; p = 0.001) using the IVW analyses, as well in the additional analyses using the weighted median and weighted-mode methods. No evidence in heterogeneity, pleiotropy or outlier single-nucleotide polymorphisms was detected (all p > 0.05). Suggestive casual association between increased genetically determined TAB Se concentrations and decreased hypothyroidism risk was found by the IVW method (odds ratio [OR] = 0.847; 95% CI = 0.728, 0.985; p = 0.031). The causal effect of TAB Se on FT4 was observed in women (ß = -.076; 95% CI = -0.129, -0.024; p = 0.004). However, the influence of genetically determined higher Se concentrations on TSH levels and hyperthyroidism revealed insignificance in the primary and sensitivity analyses. CONCLUSIONS: The present MR study indicated that high Se concentration enable the decreasing of FT4 levels, and the effects of Se concentrations on FT4 remain sex-specific.

Alpinetin alleviates osteoporosis by promoting osteogenic differentiation in BMSCs by triggering autophagy via PKA/mTOR/ULK1 signaling.

Osteoporosis, a systemic bone disease that is characterized by a reduction in bone mass and destruction of bone microstructure, is becoming a serious problem worldwide. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into bone-forming osteoblasts, and play an important role in maintaining homeostasis of bone metabolism, thus being a potential therapeutic target for osteoporosis. Although the phytochemical alpinetin (APT) has been reported to possess a variety of pharmacological activities, it is still unclear whether APT can influence the osteogenic differentiation of on BMSCs and if it can improve osteoporosis. In this study, we found that APT treatment was able to enhance osteogenic differentiation levels of human BMSCs in vitro and mouse ones in vivo as revealed by multiple osteogenic markers including increased alkaline phosphatase activity and osteocalcin expression. Mechanistically, the protein kinase A (PKA)/mTOR/ULK1 signaling was involved in the action of APT to enhance the osteogenic differentiation of BMSCs. In addition, oral administration of APT significantly mitigated the bone loss in a dexamethasone-induced mouse model of osteoporosis through strengthening PKA signaling and autophagy. Altogether, these data demonstrate that APT promotes osteogenic differentiation in BMSCs by augmenting the PKA/mTOR/ULK1 autophagy signaling, highlighting its potential therapeutic application for treating osteoporotic diseases.

Optimization for the preparation process of silver nanoparticles and their biological activity. / çº³ç±³é“¶åˆ¶å¤‡å·¥è‰ºä¼˜åŒ–åŠå ¶ç”Ÿç‰©æ´»æ€§.

OBJECTIVES: Recently, the use of biological synthesis of metal nanoparticles has attracted widespread attention. Researchers are trying to find a biological method to synthesize silver nanoparticles with little environmental pollution and easy preparation, and to explore the impact of preparation conditions on the synthesis of silver nanoparticles. This study aims to explore the biological synthesis of silver nanoparticles (AgNPs) with controllable size and good effect and to compare their biological activity with that of AgNPs prepared by chemical method. METHODS: In this study, AgNPs were prepared by biological method with water extract of Tricholomagambosum (WET) and cell-free supernatant of Lactobacillus crispatus (CFS) as reducing agent and protective agent, and silver nitrate solution as precursor. Meanwhile, AgNPs was synthesized by sodium citrate chemical method. The effects of temperature, pH, dosage of extraction solution and light conditions on the biosynthesis of WET-AgNPs and CFS-AgNPs were investigated, and their characteristic of the synthesized WET-AgNPs and CFS-AgNPs were analyzed. Finally, the antibacterial effect, toxicity and selectivity of the 3 different AgNPs were compared. RESULTS: AgNPs were synthesized successfully by the 3 methods with various characteristics. The AgNPs prepared by biological method (WET-AgNPs , CFS-AgNPs) were greatly affected by pH and temperature. The WET-AgNPs and CFS-AgNPs prepared by the biological methods had better antibacterial effect than the AgNPs by the chemical method (all P<0.01). Between them, the WET-AgNPs had a slightly higher antibacterial effect than the CFS-AgNPs. Compared with the AgNPs prepared by chemical method, the toxicity of the WET-AgNPs and CFS-AgNPs to normal cells was lower (both P<0.01), and the cell selectivity of the CFS-AgNPs was better when the concentration was 480 µg/mL. CONCLUSIONS: AgNPs with biological activity can be synthesized from WET and CFS, which have different biological activity compared with the AgNPs prepared by biological method.

[Variation Characteristics of Surface Water Quality in China in Recent Years].

Based on data from 839 comparable sections (sites) of the national surface water environmental quality monitoring network from 2012 to 2020, the variation tendency of surface water environmental quality over the past nine years was analyzed. The results showed that the environmental quality of surface water in China has continuously improved, the proportion of Grade Ⅰ-Ⅲ water quality increased steadily, and the proportion of inferior Grade Ⅴ water quality decreased in succession. The annual average concentration of ammonia nitrogen, total phosphorus, and permanganate index all showed a decreasing trend annually; compared with those in 2012, the three indicator concentrations respectively declined 75.9%, 48.2%, and 17.5% by 2020. In Guangxi, Hainan, and Ningxia, the proportion of Grade Ⅰ-Ⅲ water quality sections was maintained at 100%, whereas Hubei and Jiangxi showed a consecutive decreasing trend, and the other provinces showed a consecutive increasing trend. In Guangxi, Hainan, Ningxia, Hunan, and Fujian, the proportion of inferior Grade Ⅴ water quality sections remained at 0, and the other provinces showed a decreasing trend yearly. The annual average concentration of total phosphorus in Guangxi and Jiangxi and the permanganate index in Hubei, Hainan, and Liaoning increased annually, whereas that in the other provinces decreased to varying degrees. The proportion of Grade Ⅰ-Ⅲ water quality sections in Ten Major basins showed a fluctuating upward trend. The proportion of inferior Grade Ⅴ water quality in the Zhejiang and Fujian Slice Rivers was maintained at 0, and the other river basins showed a fluctuating and declining trend. The annual average of the main pollution indicators all decreased to varying degrees. In 2020, 53% of 32 important lakes were eutrophic, which increased 12% compared to that in 2012. On the whole, surface water quality has generally improved in China during the past nine years; especially since the 13th Five-Year Plan period, remarkable achievements have been made in the prevention and control of water pollution. However, there are differences among various provinces and basins, the improvement in water environmental quality is unbalanced and uncoordinated, water resources are distributed unevenly, and the eutrophication trend of lakes and reservoirs is not optimistic. In the future, water resources, water environment, and water ecology should be overall managed, and great attention should be focused on precise pollution control and ecological restoration of surface water.

Abnormal transcriptome-wide DNA demethylation induced by folate deficiency causes neural tube defects.

Neural tube defect (NTDs) is one of the most common and serious fetal and neonatal birth defects. Neural tube closure (NTC) is an exquisitely coordinated process and this procedure is influenced by both genetic and environmental factor. Folic acid (FA) supplementation is an effective for prevention of a proportion of NTDs, however, the mechanism remains unclear. In this study, our data demonstrated genome-wide enrichment of 5-hydroxymethylcytosine (5hmC) modification on active transcriptional start sites (TSS) and decreased 5-methylcytosine (5mC) binding to TSS under folate deficiency in mESCs (mouse embryonic stem cells). Furthermore, folate deficiency promoted 5hmC enrichment enhancer histone 3 lysine 27 acetylation (H3K27ac) binding to Shh pathway genes in mESCs. Upregulation of Shh target genes was observed in mouse brain tissue under low levels of maternal serum folate, along with increased expression of 5-methylcytosine dioxygenase Tet1 levels. Taken together, we found that folate deficiency promoted DNA demethylation and enriched 5hmC through recruitment of H3K27ac to activate the Shh signaling pathway. These results suggest that the 5hmC modification increases concomitantly with a positive correlation to Shh gene expression in folate deficiency-induced mouse NTDs.