Dual role of Nrf2/HO-1 pathway in Z-ligustilide-induced ferroptosis against AML cells.

BACKGROUND: The scarcity of drugs targeting AML cells poses a significant challenge in AML management. Z-Ligustilide (Z-LIG), a phthalide compound, shows promising pharmacological potential as a candidate for AML therapy. However, its precise selective mechanism remains unclear. PURPOSE: In order to assess the selective inducement effects of Z-LIG on ferroptosis in AML cells and explore the possible involvement of the Nrf2/HO-1 pathway in the regulation of ferroptosis. METHODS: Through in vitro cell proliferation and in vivo tumor growth tests, the evaluation of Z-LIG's anticancer activity was conducted. Ferroptosis was determined by the measurement of ROS and lipid peroxide levels using flow cytometry, as well as the observation of mitochondrial morphology. To analyze the iron-related factors, western blot analysis was employed. The up-regulation of the Nrf2/HO-1 axis was confirmed through various experimental techniques, including CRISPR/Cas9 gene knockout, fluorescent probe staining, and flow cytometry. The efficacy of Z-LIG in inducing ferroptosis was further validated in a xenograft nude mouse model. RESULTS: Our study revealed that Z-LIG specifically triggered lipid peroxidation-driven cell death in AML cells. Z-LIG downregulated the total protein and nuclear entrance levels of IRP2, resulting in upregulation of FTH1 and downregulation of TFR1. Z-LIG significantly increased the susceptibility to ferroptosis by upregulating ACSL4 levels and simultaneously suppressing the activity of GPX4. Notably, the Nrf2/HO-1 pathway displayed a twofold impact in the ferroptosis induced by Z-LIG. Mild activation suppressed ferroptosis, while excessive activation promoted it, mainly driven by ROS-induced labile iron pool (LIP) accumulation in AML cells, which was not observed in normal human cells. Additionally, Nrf2 knockout and HO-1 knockdown reversed iron imbalance and mitochondrial damage induced by Z-LIG in HL-60 cells. Z-LIG effectively inhibited the growth of AML xenografts in mice, and Nrf2 knockout partially weakened its antitumor effect by inhibiting ferroptosis. CONCLUSION: Our study presents biological proof indicating that the selective initiation of ferroptosis in leukemia cells is credited to the excessive activation of the Nrf2/HO-1 pathway triggered by Z-LIG.

Exogenous methionine contributes to reversing the resistance of Streptococcus suis to macrolides.

Streptococcus suis (S. suis) has been increasingly recognized as a porcine zoonotic pathogen that threatens the health of both pigs and humans. Multidrug-resistant Streptococcus suis is becoming increasingly prevalent, and novel strategies to treat bacterial infections caused by these organisms are desperately needed. In the present study, an untargeted metabolomics analysis showed that the significant decrease in methionine content and the methionine biosynthetic pathway were significantly affected by the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis in drug-resistant S. suis. The addition of L-methionine restored the bactericidal activity of macrolides, doxycycline, and ciprofloxacin on S. suis in vivo and in vitro. Further studies showed that the exogenous addition of methionine affects methionine metabolism by reducing S-adenosylmethionine synthetase activity and the contents of S-adenosylmethionine, S-adenosyl homocysteine, and S-ribose homocysteine. Methionine can decrease the total methylation level and methylesterase activity in multidrug resistant S. suis. The drug transport proteins and efflux pump genes were significantly downregulated in S. suis by exogenous L-methionine. Moreover, the exogenous addition of methionine can reduce the survival of S. suis by affecting oxidative stress and metal starvation in bacteria. Thus, L-methionine may influence the development of resistance in S. suis through methyl metabolism and metal starvation. This study provides a new perspective on the mitigation of drug resistance in S. suis.IMPORTANCEBacterial antibiotic resistance has become a severe threat to human and animal health. Increasing the efficacy of existing antibiotics is a promising strategy against antibiotic resistance. Here, we report that L-methionine enhances the efficacy of macrolides, doxycycline, and ciprofloxacin antibiotics in killing Streptococcus suis, including multidrug-resistant pathogens. We investigated the mechanism of action of exogenous methionine supplementation in restoring macrolides in Streptococcus suis and the role of the methionine cycle pathway on methylation levels, efflux pump genes, oxidative stress, and metal starvation in Streptococcus suis. It provides a theoretical basis for the rational use of macrolides in clinical practice and also identifies a possible target for restoring drug resistance in Streptococcus suis.

Development and validation of a deep eutectic solvent-assisted liquid-liquid extraction method for simultaneous quantification of six steroid hormones in serum by liquid chromatography-tandem mass spectrometry.

Steroid hormones have been reported to be associated with endocrine system diseases. This paper proposes a novel procedure of deep eutectic solvent (DES)-assisted liquid-liquid extraction (LLE) to extract six steroid hormones (including cortisone, cortisol, androstenedione, testosterone, 17-hydroxyprogesterone, and progesterone) from serum coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of five types of L-proline, choline chloride, and citric acid-based DESs were tailored; the DES from L-proline and ethylene glycol at a molar ratio of 1:4 with 20 % acetonitrile was selected as the best-fit assisted solvent for the six steroid hormones compared with other DESs. The parameters for extraction by selected DES were optimized using Box-Behnken design (BBD), and the optimal extraction conditions are 200 µL of acetonitrile, 100 µL of the sample, and 80 µL of DES. Under optimum conditions, the method has good linear calibration ranges (between 0.07 ng mL-1 and 600 ng mL-1), correlation coefficients of determination (r2>0.99), and low limits of quantification (between 0.02 and 0.60 ng mL-1). The extraction recoveries were in the range of 81.84-114.43 %, and the intra-day and inter-day relative standard deviations (RSDs) were less than 10 %.In general, the DES-LC-MS/MS method is a simple and environmentally-friendly method, which can be complementary to the presently available methods for determining steroid hormones in serum.

The clinical efficacy of Zuqing Xu "Wuduling" powder for snake injury on the swelling of the affected limb bitten by Agkistrodon halys.

To determine the clinical efficacy of Zuqing Xu 'Wuduling' powder for snake injury on the swelling of the affected limb bitten by Agkistrodon halys. Sixty-five patients with Agkistrodon halys bite were assigned to a treatment group (n = 35) or control group (n = 30). The treatment group was additionally given 'Wuduling' powder dressing locally based on the therapy to the control group with conventional Western medicine. Clinical efficacy and improvement of traditional Chinese medicine symptoms and signs in the two groups were evaluated. The treatment group showed a notably higher cure rate than the control group. After 3 days of therapy, the swelling and pain of the affected limb in the treatment group were greatly alleviated. Additionally, after 7 days of therapy, the swelling and pain of the affected limb in the treatment group were more greatly alleviated, and those in the control group were also alleviated. The comparison of the two groups during the same period showed more obvious alleviation of swelling and pain in the treatment group than that in the other. Moreover, the treatment group experienced notably shorter disappearing time of swelling and pain than the control group. After treatment, the levels of CRP, TBIL, Cr, ALT, AST, BUN, CK, LDH and CK-MB in both groups declined notably, with notably lower levels of them in the treatment group than those in the other. Zuqing Xu 'Wuduling' powder for snake injury can substantially alleviate the swelling and local pain of affected limbs bitten by Agkistrodon halys.

Comparative and phylogeny analysis of Asarum caudigerum and A. cardiophyllum complete chloroplast genomes / 药学学报

The complete chloroplast genome of medicinal plant Asarum caudigerum Hance and its close relative A. cardiophyllum Franchet were sequenced using Illumina Hiseq technology, and assembled, annotated, and characterized by bioinformatic methods in this study. Then phylogenetic analysis of the complete chloroplast genomes of A. caudigerum, A. cardiophyllum, and twelve published species was conducted. The results indicated that the chloroplast genomes ranged from 186 215-186 985 bp in length, with a large single copy (LSC, 89 445-90 169 bp) and two inverted repeats (IRa/IRb, 48 387-48 408 bp). The overall GC content was 37.4%-37.5%. A total of 144 chloroplast genes were annotated, including 98 protein coding genes, 38 tRNA genes and 8 rRNA genes. In addition, complex genomic rearrangements were detected in the chloroplast genome of Asarum. Meanwhile, visual evaluation of the discrete type of the sequence indicated that the variation level of non-coding region was higher than that of coding region. Phylogenetic analyses suggested that A. caudigerum and A. cardiophyllum were clustered into a single clade and A. cardiophyllum, A. sieboldii var. seoulense, A. misandrum and A. maculatum were clustered into another single branch. These two clade were sister species. This study provides a scientific basis for the identification, phylogenetic relationship, molecular breeding of Asarum species.

[Regulatory effect of five-element music therapy of traditional Chinese medicine for suboptimal health status of liver stagnation and spleen deficiency based on the temperature changes of acupoints].

OBJECTIVE: To observe the effect of five-element music therapy of traditional Chinese medicine (TCM) on the clinical symptoms and the quality of life in the patients with suboptimal health status (SHS) of liver stagnation and spleen deficiency and explore the corresponding specificity changes in the temperature of acupoints when zangfu functions are of dysfunction and recovered to be balanced, separately. METHODS: Sixty patients with SHS of liver stagnation and spleen deficiency were randomized into an observation group and a control group, 30 cases in each one. In the control group, the conventional health education was provided. In the observation group, on the base of the therapeutic regimen as the control group, the patients received the five-element music therapy to pacify the liver qi and strengthen the spleen functions, once every two days, 30 min each time, 3 treatments a week. The course of treatment consisted of 4 weeks. Before and after treatment, the TCM syndrome score and the MOS 36-item short form healthy survey (SF-36) score were compared between the two groups and the clinical therapeutic effect was evaluated. Using infrared thermal imaging, the temperature at the acupoints of the affected organs (liver, spleen), the related organs (gallbladder, stomach) and the other non-related zangfu organs (pericardium, lung) was detected before and after treatment in the two groups. RESULTS: After treatment, the TCM syndrome scores were reduced when compared with those before treatment in the two groups (P<0.01, P<0.05); the reduction in the observation group was larger than that of the control group (P<0.01). The score of each domain for the SF-36 in the observation group and the score of role-emotional domain in the control group were all increased when compared with the scores before treatment (P<0.01, P<0.05); and the score of each domain for the SF-36 in the observation group was higher than that in the control group (P<0.01). The total effective rate was 66.7% (20/30) in the observation group, which was higher than 10.0% in the control group (3/30, P<0.05). In the observation group, the temperature of the yuan-primary point, the back-shu point and the front-mu point related to the liver, as well as those related to the gallbladder after treatment was reduced when compared with the temperature before treatment; and the changes were larger than those of the control group (P<0.01). The temperature of the yuan-primary point, the back-shu point and the front-mu point related to the spleen, as well as the back-shu point and the front-mu point related to the stomach in the observation group was increased when compared with the temperature before treatment (P<0.01); and the changes were larger than those of the control group (P<0.01). For the temperature of the non-specific points related to the liver and spleen, as well as the yuan-primary point, the back-shu point and the front-mu point related to the pericardium and the lung, there was no significant differences when compared with the temperature at the above-mentioned acupoints before and after treatment (P>0.05). CONCLUSION: TCM five-element music therapy associated with the conventional health education may effectively relieve the clinical symptoms and improve the quality of life in the patients with suboptimal health status of liver stagnation and sleep deficiency; and the therapeutic effect is better than the simple health education. The changes in the temperature of acupoints may reflect the functional regulation of the related zangfu organs in the body.

Effects of Simo decoction on gastric motility of diabetic rats.

BACKGROUND: To investigate the effects of simo decoction (SMD) on the gastric motility of diabetic rats. METHODS: Diabetic rats were gavaged with various doses of SMD (0.15, 1.5, and 3.0 ml/kg/d) or saline, and their blood glucose levels and body weight were monitored. Gastric emptying and antral motility were assessed by phenol red retention and contractions of antral strips, respectively. The levels of substance P (SP), vasoactive intestinal peptide (VIP), and neurogenic nitric oxide synthase (nNOS) in the gastric antrum were determined by real-time polymerase chain reaction and Western blot. RESULTS: Gastric emptying was delayed in diabetic rats (p < 0.01 vs. non-diabetic controls) but accelerated after SMD administration (p < 0.01). The contractions of antral strips were reduced in diabetic rats (p < 0.01 vs. non-diabetic controls) but improved after SMD intervention (p < 0.05). The mRNA expressions of SP, VIP, and nNOS in diabetic rats were downregulated compared with non-diabetic controls (all p < 0.01). Simo decoction treatment did not affect the expression of these factors in diabetic rats. The protein levels of SP, VIP, and nNOS in diabetic rats were decreased (p < 0.01), increased (p < 0.01), and comparable (p > 0.05), respectively, in comparison with non-diabetic controls. Simo decoction administration increased SP protein expression (p < 0.01) and decreased the levels of VIP (p < 0.01) and nNOS (p < 0.01) in diabetic rats. CONCLUSIONS: Simo decoction improved gastric dysmotility of diabetic rats possibly by upregulating SP and downregulating VIP and nNOS.

Antifungal and Antibiofilm In Vitro Activities of Ursolic Acid on Cryptococcus neoformans.

Ursolic acid (UA) exists in a variety of medicinal plants. UA exhibits antimicrobial activity against several microorganisms; however, little is known regarding the potential antifungal effect of UA on Cryptococcus neoformans (C. neoformans). The antifungal and antibiofilm activities of UA on C. neoformans H99 were evaluated in this study. Minimum inhibitory concentration (MIC) of UA against C. neoformans H99 was determined by microdilution technique, and its action mode was elucidated by clarifying the variations in cell membrane integrity, capsule, and melanin production. Moreover, the inhibition and dispersal effects of UA on biofilm formation and mature biofilms by C. neoformans H99 were evaluated using crystal violet (CV) assay, optical microscopy, field emission scanning electron microscopy and confocal laser scanning microscopy. The results indicated that the MIC value of UA against C. neoformans H99 was 0.25 mg/mL. UA disrupted the cell membrane integrity, inhibited the capsule and melanin production of C. neoformans H99 in a concentration-dependent manner. Further, UA presented the inhibitory effect on biofilm formation and dispersed mature biofilms, as well as compromised the cell membrane integrity of C. neoformans H99 cells within biofilms. Together, these results indicate that UA might be a potential therapeutic option for the treatment of C. neoformans-related infections.

[Anti-pneumonia targets and mechanism of Xiaoer Xiaoji Zhike Oral Liquid].

This study aims to identify the anti-pneumonia targets of Xiaoer Xiaoji Zhike Oral Liquid(XXZL) with "target fishing" strategy and investigate the related signaling pathways, thereby clarifying the anti-pneumonia mechanism of XXZL. To be specific, the magnetic nanoparticles cross-linked with XXZL extract were prepared based on the photochemical activity of benzophenone, which were then used to capture the target proteins from the lysate of tissue with lipopolysaccharide(LPS)-induced pneumonia in mice. Then, the target proteins were identified by liquid chromatography-tandem mass spectrometry(LC-MS/MS). The signaling pathways and interactions of target proteins were explored with KEGG and STRING analysis on Cytoscape, and the possible biological functions of the target proteins were verified by immunohistochemistry(IHC) and RT-PCR. The result showed that LC-MS/MS identified 62 potential anti-pneumonia targets of XXZL in the lungs. The targets were involved in Ras signaling pathway, mitophagy, leukocyte transendothelial migration, mitogen-activated protein kinase(MAPK) signaling pathway, platelet activation, and actomyosin structure organization, which were closely related to inflammation, pulmonary microcirculation, pulmonary fibrosis, and energy metabolism. XXZL up-regulated the content of CD31, and heat shock protein 60(HSP60) and ATP5 b mRNA expression, down-regulated interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), COL1 A1 content, and alleviated fibrosis, which suggested the obvious effects of XXZL such as anti-inflammation, pulmonary microcirculation improvement, pulmonary fibrosis inhibition, and energy metabolism regulation. This study explained the anti-pneumonia mechanism of XXZL from targets, which can serve as a reference for the clinical application of the prescription.

Carbon Quantum Dots-Based Nanozyme from Coffee Induces Cancer Cell Ferroptosis to Activate Antitumor Immunity.

Carbon quantum dots (CQDs) offer huge potential due to their enzymatic properties as compared to natural enzymes. Thus, discovery of CQDs-based nanozymes with low toxicity from natural resources, especially daily food, implies a promising direction for exploring treatment strategies for human diseases. Here, we report a CQDs-based biocompatible nanozyme prepared from chlorogenic acid (ChA), a major bioactive natural product from coffee. We found that ChA CQDs exhibited obvious GSH oxidase-like activities and subsequently promoted cancer cell ferroptosis by perturbation of GPX4-catalyzed lipid repair systems. In vivo, ChA CQDs dramatically suppressed the tumor growth in HepG2-tumor-bearing mice with negligible side toxicity. Particularly, in hepatoma H22-bearing mice, ChA CQDs recruited massive tumor-infiltrating immune cells including T cells, NK cells, and macrophages, thereby converting "cold" to "hot" tumors for activating systemic antitumor immune responses. Taken together, our study suggests that natural product-derived CQDs from coffee can serve as biologically safe nanozymes for anticancer therapeutics and may aid the development of nanotechnology-based immunotherapeutic.

[Analysis of curative effect of ultrasonic hyperthermia combined with TPF chemotherapy on 19 elderly with advanced oral squamous cell carcinoma].

PURPOSE: To evaluate the efficacy and safety of ultrasound hyperthermia combined with TPF chemotherapy for advanced oral squamous cell carcinoma in the elderly. METHODS: Nineteen elderly patients who had definite pathological diagnosis were enrolled in this clinical trail from June 2017 to January 2020. Docetaxel (75 mg/m2) + cisplatin (75 mg/m2) were given on the 1st day , and 5,Fu (750 mg/m2) on the 1st to 5th day of the cycle. Five times of hyperthermia were performed in the course of chemotherapy, respectively on the l, 3, 5, 7 and 9 days after the beginning of chemotherapy. All patients received 2 cycles of thermo -chemotherapy. Statistical analysis was performed using SPSS 20.0 software package. Kaplan-Meire method was used to calculate survival rate. RESULTS: According to the efficacy evaluation standard for solid tumor (version 1.0), complete response (CR) was seen in 3 cases, partial response (PR) was seen in 10 cases, stable disease(SD) was seen in 5 cases，progressive disease(PD) was seen in 1 case. The overall responding rate was 68.4%. The median follow-up time was 36 months(8-48 months), and the 2-year overall survival rates were 63.2%. No serious adverse reactions were observed. CONCLUSIONS: Ultrasound hyperthermic therapy combined with chemotherapy has a synergistic anti-tumor effect on patients with advanced oral squamous cell carcinoma, which is safe and effective, and is worthy of becoming another choice of tumor treatment.

The chromosome-scale reference genome of Rubus chingii Hu provides insight into the biosynthetic pathway of hydrolyzable tannins.

Rubus chingii Hu (Fu-Pen-Zi), a perennial woody plant in the Rosaceae family, is a characteristic traditional Chinese medicinal plant because of its unique pharmacological effects. There are abundant hydrolyzable tannin (HT) components in R. chingii that provide health benefits. Here, an R. chingii chromosome-scale genome and related functional analysis provide insights into the biosynthetic pathway of HTs. In total, sequence data of 231.21 Mb (155 scaffolds with an N50 of 8.2 Mb) were assembled into seven chromosomes with an average length of 31.4 Mb, and 33 130 protein-coding genes were predicted, 89.28% of which were functionally annotated. Evolutionary analysis showed that R. chingii was most closely related to Rubus occidentalis, from which it was predicted to have diverged 22.46 million years ago (Table S8). Comparative genomic analysis showed that there was a tandem gene cluster of UGT, carboxylesterase (CXE) and SCPL genes on chromosome 02 of R. chingii, including 11 CXE, eight UGT, and six SCPL genes, which may be critical for the synthesis of HTs. In vitro enzyme assays indicated that the proteins encoded by the CXE (LG02.4273) and UGT (LG02.4102) genes have tannin hydrolase and gallic acid glycosyltransferase functions, respectively. The genomic sequence of R. chingii will be a valuable resource for comparative genomic analysis within the Rosaceae family and will be useful for understanding the biosynthesis of HTs.

Regional association analysis coupled with transcriptome analyses reveal candidate genes affecting seed oil accumulation in Brassica napus.

KEY MESSAGE: Regional association analysis of 50 re-sequenced Chinese semi-winter rapeseed accessions in combination with co-expression analysis reveal candidate genes affecting oil accumulation in Brassica napus. One of the breeding goals in rapeseed production is to enhance the seed oil content to cater to the increased demand for vegetable oils due to a growing global population. To investigate the genetic basis of variation in seed oil content, we used 60 K Brassica Infinium SNP array along with phenotype data of 203 Chinese semi-winter rapeseed accessions to perform a genome-wide analysis of haplotype blocks associated with the oil content. Nine haplotype regions harbouring lipid synthesis/transport-, carbohydrate metabolism- and photosynthesis-related genes were identified as significantly associated with the oil content and were mapped to chromosomes A02, A04, A05, A07, C03, C04, C05, C08 and C09, respectively. Regional association analysis of 50 re-sequenced Chinese semi-winter rapeseed accessions combined with transcriptome datasets from 13 accessions was further performed on these nine haplotype regions. This revealed natural variation in the BnTGD3-A02 and BnSSE1-A05 gene regions correlated with the phenotypic variation of the oil content within the A02 and A04 chromosome haplotype regions, respectively. Moreover, co-expression network analysis revealed that BnTGD3-A02 and BnSSE1-A05 were directly linked with fatty acid beta-oxidation-related gene BnKAT2-C04, thus forming a molecular network involved in the potential regulation of seed oil accumulation. The results of this study could be used to combine favourable haplotype alleles for further improvement of the seed oil content in rapeseed.

Combining quantitative trait locus and co-expression analysis allowed identification of new candidates for oil accumulation in rapeseed.

In crops there are quantitative trait loci (QTLs) in which some of the causal quantitative trait genes (QTGs) have not been functionally characterized even in the model plant Arabidopsis. We propose an approach to delineate QTGs in rapeseed by coordinating expression of genes located within QTLs and known orthologs related to traits from Arabidopsis. Using this method in developing siliques 15 d after pollination in 71 lines of rapeseed, we established an acyl-lipid metabolism co-expression network with 21 modules composed of 270 known acyl-lipid genes and 3503 new genes. The core module harbored 76 known genes involved in fatty acid and triacylglycerol biosynthesis and 671 new genes involved in sucrose transport, carbon metabolism, amino acid metabolism, seed storage protein processes, seed maturation, and phytohormone metabolism. Moreover, the core module closely associated with the modules of photosynthesis and carbon metabolism. From the co-expression network, we selected 12 hub genes to identify their putative Arabidopsis orthologs. These putative orthologs were functionally analysed using Arabidopsis knockout and overexpression lines. Four knockout mutants exhibited lower seed oil content, while the seed oil content in 10 overexpression lines was significantly increased. Therefore, combining gene co-expression network analysis and QTL mapping, this study provides new insights into the detection of QTGs and into acyl-lipid metabolism in rapeseed.

Transcriptome sequencing and metabolome analysis reveal the mechanism of Shuanghua Baihe Tablet in the treatment of oral mucositis / 中国天然药物

Oral mucositis (OM) caused by cancer therapy is the most common adverse reaction in the radiotherapy of head and neck tumors. In severe cases, it can lead to the interruption of treatment, which affects the control of the disease and the quality of life. Shuanghua Baihe Tablet (SBT) is a traditional Chinese medicine (TCM) formula, which is administerd to treat OM in China. It has been clinically effective for more than 30 years, but the underlying mechanism is not completely understood. With the development of multiple omics, it is possible to explore the mechanism of Chinese herbal compound prescriptions. Based on transcriptomics and metabolomics, we explored the underlying mechanism of SBT in the treatment of OM. An OM model of rats was established by 5-FU induction, and SBT was orally administered at dosages of 0.75 and 3 g·kg

Increased thalamic volume and decreased thalamo-precuneus functional connectivity are associated with smoking relapse.

The thalamus, with the highest density of nicotinic acetylcholine receptor (nAChR) in the brain, plays a central role in thalamo-cortical circuits that are implicated in nicotine addiction. However, little is known about whether the thalamo-cortical circuits are potentially predictive of smoking relapse. In the current study, a total of 125 participants (84 treatment-seeking male smokers and 41 age-matched male nonsmokers) were recruited. Structural and functional magnetic resonance images (MRI) were acquired from all participants. After a 12-week smoking cessation treatment with varenicline, the smokers were then divided into relapsers (n = 54) and nonrelapsers (n = 30). Then, we compared thalamic volume and seed-based thalamo-cortical resting state functional connectivity (rsFC) prior to the cessation treatment among relapsers, nonrelapsers and nonsmokers to investigate the associations between thalamic structure/function and smoking relapse. Increased thalamic volume was detected in smokers relative to nonsmokers, and in relapsers relative to nonrelapsers, especially on the left side. Moreover, decreased left thalamo-precuneus rsFC was detected in relapsers relative to nonrelapsers. Additionally, a logistic regression analysis showed that the thalamic volume and thalamo-precuneus rsFC predicted smoking relapse with an accuracy of 75.7%. These novel findings indicate that increased thalamic volume and decreased thalamo-precuneus rsFC are associated with smoking relapse, and these thalamic measures may be used to predict treatment efficacy of nicotine addiction and serve as a potential biomarker for personalized medicine.

A New Therapy for Vitiligo Using Fire Needles: A Systematic Review of Evidence from 3618 Subjects.

INTRODUCTION: Fire needle therapy has been reported as an effective treatment for vitiligo. However, current clinical evidence has not been systematically evaluated. The aim of this study was to determine whether fire needle therapy is effective and safe for treating vitiligo. METHODS: Seven databases were searched until October 2019 for randomized controlled trials on fire needle therapy, with and without conventional treatments, versus any type of conventional therapy for treating vitiligo. The RevMan 5.3.5 software was used to perform meta-analysis of the included studies. RESULTS: Forty-seven trials comprising 3618 patients were included. Fire needle combined with conventional vitiligo treatments had a higher efficacy (risk ratio (RR): 1.55, 95% confidence interval (CI): 1.46-1.65, P < 0.00001 and RR: 1.41, 95% CI: 1.24-1.61, P < 0.00001, respectively) and a greater effect on restoring the color of the area of the skin lesion (mean difference (MD): 3.40, 95% CI: 2.11-4.69, P < 0.00001), increasing the pigment point of vitiligo (MD: 0.83, 95% CI: 0.54-1.13, P < 0.00001) and improving the cytokine level (MD: 8.10, 95% CI: 6.94-9.27, P < 0.00001) and effectual time (MD: -4.76, 95% CI: -7.33 to -2.19, P=0.0003) than traditional methods. Limb lesions (RR: 1.60, 95% CI: 1.31-1.95, P < 0.00001) were more effectively treated when the treatments included fire needles, whereas the therapeutic effect of fire needles on either the head and neck (RR: 1.13, 95% CI: 0.78-1.64, P=0.52) or torso lesions (RR: 1.22, 95% CI: 0.82-1.81, P=0.33) was not significantly different compared to that without fire needles. No statistically significant differences in adverse effects (RR: 1.15, 95% CI: 0.89-1.49, P=0.28) and recurrence rates (RR: 0.90, 95% CI: 0.17-4.92, P=0.91) during the follow-up period were observed between treatment with and without fire needles. CONCLUSIONS: Fire needle therapy combined with other conventional treatments is useful in treating vitiligo. Further studies with larger sample sizes should be performed to make a conclusive judgment. This trial is registered with CRD42018094918.

A multifunctional platform with single-NIR-laser-triggered photothermal and NO release for synergistic therapy against multidrug-resistant Gram-negative bacteria and their biofilms.

BACKGROUND: Infectious diseases caused by multidrug-resistant (MDR) bacteria, especially MDR Gram-negative strains, have become a global public health challenge. Multifunctional nanomaterials for controlling MDR bacterial infections via eradication of planktonic bacteria and their biofilms are of great interest. RESULTS: In this study, we developed a multifunctional platform (TG-NO-B) with single NIR laser-triggered PTT and NO release for synergistic therapy against MDR Gram-negative bacteria and their biofilms. When located at the infected sites, TG-NO-B was able to selectively bind to the surfaces of Gram-negative bacterial cells and their biofilm matrix through covalent coupling between the BA groups of TG-NO-B and the bacterial LPS units, which could greatly improve the antibacterial efficiency, and reduce side damages to ambient normal tissues. Upon single NIR laser irradiation, TG-NO-B could generate hyperthermia and simultaneously release NO, which would synergistically disrupt bacterial cell membrane, further cause leakage and damage of intracellular components, and finally induce bacteria death. On one hand, the combination of NO and PTT could largely improve the antibacterial efficiency. On the other hand, the bacterial cell membrane damage could improve the permeability and sensitivity to heat, decrease the photothermal temperature and avoid damages caused by high temperature. Moreover, TG-NO-B could be effectively utilized for synergistic therapy against the in vivo infections of MDR Gram-negative bacteria and their biofilms and accelerate wound healing as well as exhibit excellent biocompatibility both in vitro and in vivo. CONCLUSIONS: Our study demonstrates that TG-NO-B can be considered as a promising alternative for treating infections caused by MDR Gram-negative bacteria and their biofilms.

Baicalin Inhibits Coxsackievirus B3 Replication by Reducing Cellular Lipid Synthesis.

Baicalin is a flavonoid extracted from Scutellariae Radix and shows a variety of biological activities as reducing lipids, diminishing inflammation, and inhibiting bacterial infection. However, there is no report of baicalin against CVB3 infection. In this study, we found that baicalin can reduce viral titer in a dose-dependent manner in vitro at a dose with no direct virucidal effect. Moreover, we revealed that baicalin can also improve survival rate, reduce heart weight/body weight ratio, prevent virus replication, and relieve myocardial inflammation in the acute viral myocarditis mouse model induced by CVB3. Then, in order to explore the mechanism of baicalin inhibiting CVB3 replication, we respectively examined the expression of autophagosome marker LC3-II by Western blot, tested the concentration of free fatty acid (FFA) and cholesterol (CHO) by commercial kits, detected the mRNA levels of fatty acid synthase (Fasn) and acetyl coenzyme a carboxylase (ACC) by RT-PCR, and observed the lipid content of cells by fluorescence staining. The results showed that CVB3 infection increased autophagosome formation and lipid content in HeLa cells, but these changes were significantly blocked by baicalin. Finally, in order to confirm that baicalin inhibits viral replication and reduces autophagosome formation by reducing cellular lipids, we added exogenous palmitate to cell culture supernatants to promote intracellular lipid synthesis and found that palmitate did not alter LC3-II and CVB3/VP1 expression in HeLa cells with or without CVB3 infection. Interestingly, palmitate can reverse the inhibitory effect of baicalin on autophagosome formation and viral replication. In conclusion, our results indicated that lipids play an important role in CVB3 replication, and the effect of baicalin against CVB3 was associated with its ability to reduce cellular lipid synthesis to limit autophagosome formation.

Analysis of the influence of the psychology changes of fear induced by the COVID-19 epidemic on the body: COVID-19.

In this paper, the theory of " Fear injury kidney " in traditional Chinese medicine is systematically reviewed, and it is found that long-term or excessive psychological changes of fear are likely to damage kidney qi and kidney essence. On this basis, the psychological studies of patients, medical staff and the public during the COVID-19 epidemic in China were analyzed, and fear psychology was found to be prevalent among all kinds of people. Modern researches on "Fear injury kidney" have also found that long-term or excessive fear could cause changes in the neuro-endocrine-immune system, which can induce diseases or susceptibility to some diseases. Therefore, during or after the prevalence of COVID-19, different groups of people may have emotional reactions such as stress and fear, which should be paid long-term attention, and the influence of fear on the body cannot be ignored. According to the change rule of psychological state under stress reaction, we should actively respond to and take psychological crisis intervention measures in time to reduce the harm of psychological stress to the body.