Effect and mechanism of acupuncture on airway smooth muscle relaxation during acute asthma attack in rats. / é’ˆåˆºæ¾å¼›å“®å–˜æ€¥æ€§å‘ä½œå¤§é¼ æ°”é“å¹³æ»‘è‚Œçš„ä½œç”¨æœºåˆ¶.

OBJECTIVES: To explore the effect and mechanism of acupuncture at "Feishu" (BL 13) and "Dingchuan" (EX-B 1), and "Kongzui" (LU 6) and "Yuji" (LU 10) for relaxing the airway smooth muscle in the rats during acute asthma attack and compare the effect among the two pairs of acupoints and the acupoints combination. METHODS: Forty SD male rats with SPF grade were randomly divided into a blank group, a model group, a pair-point A group (acupuncture at "Feishu" [BL 13] and "Dingchuan" [EX-B 1]), a pair-point B group (acupuncture at "Kongzui" [LU 6] and "Yuji" [LU 10]) and a point combination group (acupuncture at "Feishu" [BL 13] , "Dingchuan" [EX-B 1], "Kongzui" [LU 6] and "Yuji" [LU 10]), with 8 rats in each group. Except the rats in the blank group, the model of acute asthma attack was induced by ovalbumin (OVA) combined with aluminum hydroxide gel in the rest groups. Started on the 15th day of modeling, except in the blank group and the model group, acupuncture was delivered in the other groups, 30 min in each intervention, once daily, for 14 days. In each group, the latent period of asthma inducing was measured; the lung resistance (LR) and dynamic lung compliance (Cdyn) were determined using lung function detector; the levels of endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in serum and bronchoalveolar lavage fluid (BALF) were measured by ELISA; with Masson staining and electron microscopy adopted, the morphology and ultrastructure of airway smooth muscle of the rats were observed; the mRNA and protein expressions of ET-1 and beta-2 adrenergic receptor (ß2-AR) were detected by quantitative real-time fluorescence and Western blot, respectively. RESULTS: Compared with the blank group, the latent period of asthma inducing was shortened (P<0.05), RL increased and Cdyn decreased (P<0.05) with the different concentrations of methacholine (0.025 mg/kg, 0.05 mg/kg, 0.1 mg/kg, 0.2 mg/kg) in the model group. In the pair-point A group, the pair-point B group and the point combination group, the latent period of asthma inducing was prolonged (P<0.05), RL decreased and Cdyn increased (P<0.05) with different concentrations of methacholine when compared with those in the model group; and the latent period of asthma inducing in the point combination group was longer than that in the pair-point A group (P<0.05). Compared with the blank group, the levels of ET-1, TNF-α and cGMP in the serum and BALF were elevated (P<0.05), and those of cAMP reduced (P<0.05) in the model group. The levels of ET-1, TNF-α and cGMP in the serum and BALF were reduced (P<0.05), and those of cAMP elevated (P<0.05) in the pair-point A group, the pair-point B group and the point combination group when compared with those in the model group. In the blank group, the lung tissue was normal structurally. In the model group, the collagen fibers were proliferated increasingly, the smooth muscle was thickened, the mitochondria were swollen, and their cristae disrupted and reduced massively. In the pair-point B group, the collagen fibers were proliferated, the smooth muscle was thicker compared with that in the blank group, the mitochondria were mildly swollen and their cristae disrupted partially. In the pair-point A group and the point combination group, the lung tissue changes were obviously alleviated in comparison with the model group, the mitochondria were slightly swollen and their cristae disrupted occasionally. Compared with the blank group, the mRNA and protein expression of ET-1 increased and that of ß2-AR decreased in the lung tissue of the model group (P<0.05). In the pair-point A group, the pair-point B group and the point combination group, the mRNA and protein expression of ET-1 was reduced and that of ß2-AR elevated in the lung tissue when compared with those in the model group (P<0.05). In comparison with the pair-point A group, the mRNA expression of ß2-AR was elevated in the point combination group (P<0.05). When compared with the pair-point B group, the mRNA expression of ß2-AR increased, the protein expression of ET-1 decreased (P<0.05) in the point combination group. CONCLUSIONS: Acupuncture at "Feishu" (BL 13) and "Dingchuan" (EX-B 1), "Kongzui" (LU 6) and "Yuji" (LU 10), two pairs of acupoints relieves the airway smooth muscle spasm in the rats during acute asthma attack, which may be related to inhibiting the mRNA and protein expression of ET-1 to reduce the excretion of ET-1 and TNF-α; while enhancing the mRNA and protein expression of ß2-AR to balance the levels of cAMP and cGMP. The effect is optimal when acupuncture is delivered at two pairs of acupoints simultaneously.

The Potential Value of Paraspinal Nerve Block (PVB) in Percutaneous Nephrolithotomy (PCNL) Compared with General Anesthesia and Epidural Anesthesia.

Objective: To analyze the potential value of paraspinal nerve block (PVB) in percutaneous nephrolithotomy (PCNL) and to compare it with general anesthesia and epidural anesthesia. Methods: 120 patients undergoing PCNL surgery in Shanghai Jiao Tong University Affiliated Sixth People's Hospital from January 2021 to June 2022 were selected and divided into PVB anesthesia group, general anesthesia group, and epidural anesthesia group according to different anesthesia methods, with 40 cases in each group. The anesthesia index (anesthesia operation time, anesthetic effect time, anesthesia time), the vital signs (heart rate, mean arterial pressure), postoperative pain [visual analog scale (VAS)], stress response index (cortisol and noradrenaline), the incidence of adverse reactions (nausea and vomiting, lethargy, dizziness, skin itching, bradycardia) were compared among the three groups. Results: The operation time of the anesthesia in the PVB anesthesia group was 5.72±1.25, which was significantly lower than that in the the general (7.95±1.15) and epidural anesthesia groups(8.23±1.43), and the differences were statistically significant (P = .000). The time of onset of anesthesia in the PVB anesthesia group was 6.63±1.87, which was significantly lower than that in the the general (9.84±2.41) and epidural anesthesia groups(10.14±2.89), and the differences were statistically significant (P = .000).The heart rate during percutaneous puncture and intraoperative lithotripsy in the PVB anesthesia group was statistically lower than in the general and epidural anesthesia groups (P < .05). The mean arterial pressure 20 minutes after anesthesia and at the end of operation in the PVB anesthesia group was higher than that in the general anesthesia group, and the mean arterial pressure during percutaneous puncture and intraoperative lithotomy was lower than that in the general anesthesia group (P < .05). The VAS scores of the PVB anesthesia group at 2, 6, 12, 24, and 48 hours after the operation were lower than those of general and epidural anesthesia groups (P < .05). The incidence of adverse reactions was 5.00% (2/40) in the PVB anesthesia group and 35.00% (14/40) in the general anesthesia group, which was lower than that of 27.50% (11/40) in the epidural anesthesia group. (P < .05). Conclusion: The potential value of PVB in PCNL is high is better than that of general anesthesia and epidural anesthesia, anesthesia can shorten operation time and work time, extend the time of anesthesia to maintain, and be helpful to the intraoperative vital signs in patients with stable, mild postoperative pain and stress, low incidence of adverse reactions, efficacy and safety are good, can be introduced.

Licorice flavonoid ameliorates ethanol-induced gastric ulcer in rats by suppressing apoptosis via PI3K/AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is the dry roots and rhizomes of Glycyrrhiza uralensis Fisch., Glycyrrhiza glabra L. and Glycyrrhiza inflata Bat., which was first recorded in Shengnong's herbal classic. Licorice flavonoid (LF) is the main compound isolated from licorice with an indispensable action in treating gastric ulcer (GU). However, the underlying mechanisms need to be further explored. AIM OF THE STUDY: This study aimed to investigate and further elucidate the mechanisms of LF against ethanol-induced GU using an integrated approach. MATERIALS AND METHODS: The anti-GU effects of LF were evaluated in an ethanol-induced gastric injury rat model. Then, the metabolomics approach was applied to explore the specific metabolites and metabolic pathways. Next, the network pharmacology combined with metabolomics strategy was employed to predict the targets and pathways of LF for GU. Finally, these predictions were validated by molecular docking, RT-qPCR, and western blotting. RESULTS: LF had a positive impact on gastric injury and regulated the expression of GU-related factors. Upon serum metabolomics analysis, 25 metabolic biomarkers of LF in GU treatment were identified, which were primarily involved in amino acid metabolism, carbohydrate metabolism, and other related processes. Subsequently, a "components-targets-metabolites" network was constructed, revealing six key targets (HSP90AA1, AKT1, MAPK1, EGFR, ESR1, PIK3CA) that may be associated with GU treatment. More importantly, KEGG analysis highlighted the importance of the PI3K/AKT pathway including key targets, as a critical route through which LF exerted its anti-GU effects. Molecular docking analyses confirmed that the core components of LF exhibited a strong affinity for key targets. Furthermore, RT-qPCR and western blotting results indicated that LF could reverse the expression of these targets, activate the PI3K/AKT pathway, and ultimately reduce apoptosis. CONCLUSION: LF exerted a gastroprotective effect against gastric ulcer induced by ethanol, and the therapeutic mechanism may involve improving metabolism and suppressing apoptosis through the PI3K-AKT pathway.

Label-free and highly-sensitive detection of calcium ions using a silicon-on-sapphire light-addressable potentiometric sensor.

BACKGROUND: Ionic calcium (Ca2+) plays a crucial role in maintaining normal physiological and biochemical functions within the human body. Detecting the concentration of Ca2+ is of utmost significance for various purposes, including disease screening, cellular metabolism research, and evaluating drug effectiveness. However, current detection approaches such as fluorescence and colorimetry face limitations due to complex labeling techniques and the inability to track changes in Ca2+ concentration. In recent years, extensive research has been conducted in this field to explore label-free and efficient approaches. RESULTS: In this study, a novel light-addressed potentiometric sensor (LAPS) using silicon-on-sapphire technology, has been successfully developed for Ca2+ sensing. The Ca2+-sensitive LAPS achieved a wide-range detection of Ca2+, ranging from 10-2 M to 10-7 M, with an impressive detection limit of 100 nM. These advancements are attributed to the ultra-thin silicon layer, silicon dioxide layer, and solid-state silicon rubber sensitive membrane around 6 µm. Furthermore, the sensor demonstrated the ability to dynamically monitor fluctuations in Ca2+ concentration ranging from 10-9 M to 10-2 M within a solution. Its remarkable selectivity, specificity, and long-term stability have facilitated its successful application in the detection of Ca2+ in human serum and urine. SIGNIFICANCE AND NOVELTY: This work presents a Ca2+-sensitive sensor that combines a low detection limit and a wide detection range. The development represents the emergence of a label-free and rapid Ca2+ detection tool with immense prospects in home-based health monitoring, community disease screening, as well as cellular metabolism, and drug screening evaluations.

[Analysis on Driving Factors, Reduction Potential, and Environmental Effect of Inorganic Fertilizer Input in Chongqing].

In this study, we sought to quantify the effect of planting structure change on fertilizer input and environmental cost in Chongqing and develop scientific and rational strategies for chemical fertilizer reduction. Based on the crop fertilizer quota standard and large sample farmer survey data under the medium productivity level in Chongqing, we evaluated and analyzed the application reduction potential and environmental benefits of fertilizer with the difference method and life cycle assessment. The results showed that:① since Chongqing became a municipality directly under the central government (1997), Chongqing crop planting structure had greatly changed, and the proportion of food crop (rice, corn, wheat, bean, and potato) decreased by 21%. The area of fruits and vegetables increased from 3.36×105 hm2 to 1.05×106 hm2, and their proportion increased by 20%. ② Nearly 55% of fertilizers had been consumed by vegetable (37%) and citrus production systems, and 11%, 12%, and 12% of fertilizers were consumed by rice, corn, and potato, respectively. ③ The total fertilizer reduction of the Chongqing planting industry could reach up to 1.69×105 tons during the period of "the 14th Five-Year Plan," with a fertilizer reduction potential of 18.6%. The fertilizer reduction potential (reduction amount) of rice, corn, citrus, and vegetables would reach 0.3% (2.9×102 tons), 12% (1.45×104 tons), 21% (3.65×104 tons), and 30% (1.18×105 tons), respectively. On the other hand, the rape system was insufficient in phosphorus potassium fertilizers, and the corn tended to be insufficient in potash fertilizer. ④ The current production level was low, and the nitrogen loss, greenhouse gas emissions, and eutrophication potential in the planting industry of Chongqing reached 1.81×105 tons (N), 1.43×107 tons (CO2-eq), and 1.74×105 tons (PO4-eq). With the increase in the realization degree of the crop quota standard (60%-100%), the reactive nitrogen loss, greenhouse gas emissions, and eutrophication potential decreased by 14.9%-24.9%, 10.1%-16.7%, and 13.8%-23%, respectively. The structure of the planting industry in Chongqing significantly changed, the total fertilizer consumption in Chongqing tended to decline gradually, and the fertilization intensity of commercial crops stayed at a high level. The agricultural fertilizer reduction potential and the reactive nitrogen and greenhouse gas emission reduction potential were large, especially for citrus and vegetable production systems. However, it is also necessary to pay attention to insufficient corn potash fertilizer and rape phosphorus potassium fertilizer investment and carry out collaborative promotion of fertilizer reduction.

Dual-wavelength responsive CuS@COF nanosheets for high-performance photothermal/photodynamic combination treatments.

Photothermal therapy (PTT) makes it difficult to achieve good performance on tumor treatments due to insufficient photothermal conversion efficiency, etc. Combining PTT with photodynamic therapy (PDT) and other therapeutic tools can significantly enhance the tumor-killing ability and has been widely used in the development of therapeutic platforms. Copper sulfide nanoparticle (CuS NP) photothermal reagents have the advantages of low toxicity and simple synthesis; therefore, combining CuS NPs with PDT photosensitizers is an effective strategy to construct a PTT/PDT combination therapeutic platform. However, PDT photosensitizers and photothermal agents generally assembled through hydrophobic interaction, suffer from low coating efficiency or the risk of drug leakage, thus seriously restricting their applications. To address these challenges, CuS NPs with excellent photothermal conversion performance were selected as the core material to prepare CuS@COF nanosheets through a dual-ligand assistant strategy with 4,7-bis(4-aminophenyl)-2,1,3-benzothiadiazole (BTD) and 2,4,6-trihydroxybenzene-1,3,5-tricarbaldehyde (TP). As a PTT/PDT combination therapeutic platform, CuS@COF nanosheets possess a porous TP-BDT-based COF shell, and it can sufficiently contact oxygen to provide high singlet oxygen (1O2) yield under 505 nm laser irradiation. Upon illumination with a 1064 nm laser, CuS@COF nanosheets can effectively convert the photon energy into thermal energy with a photothermal conversion efficiency of 63.4%. The results of the CCK8 experiment showed that the phototoxicity of the PTT/PDT combination treatment reached 85.1%, which was much higher than the effect of a single treatment. It was also confirmed in vivo that the tumor inhibition effect of the PDT/PTT combination treatment group was much greater than that of the single treatment group.

Licorice flavonoid alleviates gastric ulcers by producing changes in gut microbiota and promoting mucus cell regeneration.

Licorice flavonoid (LF) is the main component of Glycyrrhizae Radix et Rhizoma, a "medicine food homology" herbal medicine, which has anti-digestive ulcer activity, but the mechanism in anti-gastric ulcer (GU) remains to be elucidated. In this study, we manifested that LF increased the viability of human gastric mucosal epithelial (GES-1) cells, attenuated ethanol (EtOH)-induced manifestations, reduced histological injury, suppressed inflammation, and restored gastric mucosal barrier in GU rats. After LF therapy, the EtOH-induced gut dysbiosis was partly modulated, and short-chain fatty acids (SCFAs) like butyric acid, propionic acid, and valeric acid were found in higher concentrations. We discovered that the majority of genera that increased in the GU group had a negative correlation with SCFAs in the intestinal tract. In addition, LF-upregulated SCFAs boosted mucus secretion in the gastric epithelium and the expression of mucoprotein (MUC) 5AC and MUC6, particularly the MUC5AC in the gastric foveola. Moreover, LF triggered the EGFR/ERK signal pathway which promoted gastric mucus cell regeneration. Therefore, the findings indicated that LF could inhibit inflammation, promote mucosal barrier repair and angiogenesis, regulate gut microbiota and SCFA metabolism; more importantly, promote epithelial proliferation via activation of the EGFR/ERK pathway, exerting a protective and regenerative effect on the gastric mucosa.

[Effects of acupuncture on pulmonary function and airway smooth muscle spasm in asthma rats].

OBJECTIVE: To observe the effects of acupuncture at "Kongzui" (LU 6) and "Yuji" (LU 10) on the latent period of inducing asthma, pulmonary function and the expression of endothelin-1 (ET-1) and metallothionein-2 (MT-2) in asthma rats, and to explore the possible mechanism of acupuncture in alleviating airway smooth muscle spasm and improving the acute attack of asthma. METHODS: A total of 40 male SD rats of SPF-grade were randomly divided into a normal group, a model group, a medication group and an acupuncture group, 10 rats in each group. Except for the normal group, ovalbumin sensitization method was used to establish the asthma model in the other 3 groups. Salbutamol nebulization was adopted in the medication group, while acupuncture was applied at bilateral "Kongzui" (LU 6) and "Yuji" (LU 10) in the acupuncture group. The intervention was given once a day for 14 days in the two groups. The latent period of inducing asthma and pulmonary function were observed, the levels of ET-1 and tumor necrosis factor (TNF)-α in serum and bronchoalveolar lavage fluid (BALF) were detected by ELISA method, the morphology of the airway was observed by Masson staining, the ultrastructure of the airway smooth muscle was observed by transmission electron microscopy, the mRNA and protein expression of ET-1 and MT-2 in lung tissue was detected by real-time PCR and Western blot methods. RESULTS: Compared with the normal group, in the model group, the latent period of inducing asthma was shortened (P<0.01); the airway resistance (RL) was increased while the dynamic compliance (Cdyn) was decreased (P<0.01, P<0.05); the levels of ET-1 and TNF-α in serum and BALF were increased (P<0.01); collagen fibers and collagen depositions were found around the bronchi, airway smooth muscle was thickened, the cell damage was severe and mitochondria were swollen; the mRNA and protein expression of ET-1 was increased while the mRNA and protein expression of MT-2 was decreased (P<0.01). Compared with the model group, in the acupuncture group, the latent period of inducing asthma was prolonged (P<0.05), the RL was decreased while the Cdyn was increased (P<0.01, P<0.05). Compared with the model group, in the medication group and the acupuncture group, the levels of ET-1 and TNF-α in serum and BALF were decreased (P<0.01, P<0.05); collagen fibers and collagen depositions around the bronchi were reduced, the thickened airway smooth muscle was lightened, the cell damage was improved; the mRNA and protein expression of ET-1 was decreased while the mRNA and protein expression of MT-2 was increased (P<0.01). Compared with the medication group, the mRNA expression of MT-2 was increased in the acupuncture group (P<0.05). CONCLUSION: Acupuncture at "Kongzui" (LU 6) and "Yuji" (LU 10) can improve the pulmonary function and alleviate the airway smooth muscle spasm in rats with asthma. Its mechanism may be related to the down-regulation of ET-1 expression and up-regulation of MT-2 expression.

p-Synephrine ameliorates alloxan-induced diabetes mellitus through inhibiting oxidative stress and inflammation via suppressing the NF-kappa B and MAPK pathways.

Oxidative stress and inflammation play important roles in the development of diabetes mellitus. p-Synephrine, the primary pharmacologically active protoalkaloid in Citrus species, has been popularly consumed as a dietary supplement for weight loss management. However, the effects of p-synephrine on diabetes mellitus and the action mechanisms have not been clearly elucidated. In this study, the in vitro antioxidant effects of p-synephrine were evaluated. The data showed that p-synephrine treatment exhibited significant scavenging effects against DPPH, ABTS and OH radicals and showed high reducing power. Diabetic mice were developed by alloxan injection, followed by p-synephrine administration to investigate its hypoglycemic effects in vivo. The results showed that p-synephrine intervention significantly prevented alloxan-induced alteration in body weight, organ indexes, serum uric acid content and serum creatinine content. Meanwhile, p-synephrine application significantly improved the lipid profiles, superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) contents in the serum and kidneys of diabetic mice and reduced the malondialdehyde (MDA) content in the serum of diabetic mice. Further assays suggested that p-synephrine treatment improved alloxan-induced decreases of glucose tolerance and insulin sensitivity. Also, p-synephrine supplementation altered histopathological changes in the kidneys and interscapular brown adipose tissues in diabetic mice. In addition, p-synephrine administration inhibited renal inflammation through suppressing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) gene expression levels, as well as CD45 expression levels. The anti-inflammatory effects were probably involved in the regulation of nuclear factor-κB (NF-κB) activation and mitogen-activated protein kinase (MAPK) phosphorylation. In conclusion, p-synephrine application significantly ameliorated alloxan-induced diabetes mellitus by inhibiting oxidative stress via suppressing the NF-κB and MAPK pathways.

Analysis of water quality indexes and their relationships with vegetation using self-organizing map and geographically and temporally weighted regression.

Natural vegetation has been proved to promote water purification in previous studies, while the relevant laws has not been excavated systematically. This research explored the relationships between vegetation cover and water quality indexes in Liaohe River Basin in China combined with self-organizing map (SOM) and geographically and temporally weighted regression (GTWR) innovatively and systematically based on the distributing heterogeneity of water quality conditions. Results showed that the central and northeast regions of the study area had serious organic and nutrient pollution, which needed targeted treatment. And SOM verified that high vegetation coverage with retention potential of organic and inorganic pollutants as well as nutrients improved water quality to some degree, while the excessive discharges of pollutants still had serious threats to nearby water environment despite the purification function of vegetation. GTWR indicated that the waterside vegetation was beneficial for dissolved oxygen increasing and contributed to the decreasing of organic pollutants and inorganic pollutants with reducibility. Natural vegetation also obsorbed nutrients like TN and TP to some degree. However, the retential potential of nitrogen and organic pollutants became not obvious when there were heavy pollution, which demonstrated that pollution sources should be controlled despite the purification function of vegetation. This study implied that natural vegetation purified water quality to some degree, while this function could not be revealed when there was too heavy pollution. These findings underscore that the pollutant discharge should be controlled though the natural vegetation in ecosystem promoted the purification of water bodies.

Impacts of land uses on spatio-temporal variations of seasonal water quality in a regulated river basin, Huai River, China.

Land use impacts from agriculture, industrialization, and human population should be considered in surface water quality management. In this study, we utilized an integrated statistical analysis approach mainly including a seasonal Mann-Kendall test, clustering analysis, self-organizing map, Boruta algorithm, and positive matrix factorization to the assessment of the interactions between land use types and water quality in a typical catchment in the Huai River Basin, China, over seven years (2012-2019). Spatially, water quality was clustered into three groups: upstream, midstream, and downstream/mainstream areas. The water quality of upstream sites was better than of mid-, down-, and mainstream. Temporally, water quality did not change significantly during the study period. However, the temporal variation in water quality of up-, down-, and mainstream areas was more stable than in the midstream. The interactions between land use types and water quality parameters at the sub-basin scale varied with seasons. Increasing forest/grassland areas could substantially improve the water quality during the wet season, while nutrients such as phosphorus from cropland and developed land was a driver for water quality deterioration in the dry season. Water area was not a significant factor influencing the variations of ammonia nitrogen (NH3-N) and total phosphorus (TP) in the wet or dry season, due to the intensive dams and sluices in study area. The parameters TP, and total nitrogen (TN) were principally linked with agricultural sources in the wet and dry seasons. The parameters NH3-N in the dry season, and chemical oxygen demand (CODCr) in the wet season were mainly associated with point source discharges. Agricultural source, and urban point source discharges were the main causes of water quality deterioration in the study area. Collectively, these results highlighted the impacts of land use types on variations of water quality parameters in the regulated basin.

Licochalcone B induces DNA damage, cell cycle arrest, apoptosis, and enhances TRAIL sensitivity in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a highly fatal disease recognized as a growing global health crisis. Traditional Chinese herbal medicines have been used to treat patients with cancer for many years in China. This study investigated the effects of licochalcone B (LCB), a flavonoid compound isolated from the root of Glycyrrhiza uralensis Fisch., on cell proliferation, DNA damage and TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in HCC cells. Our results showed that LCB inhibited cell proliferation and induced DNA damage, cell cycle arrest and apoptosis. Treatment with LCB significantly inhibited the Akt/mTOR pathway and activated endoplasmic reticulum (ER) stress and mitogen-activated protein kinase (MAPK) signaling pathway. Moreover, combined treatment with LCB and TRAIL yielded evident enhancements in the viability reduction and apoptosis. LCB upregulated death receptor 4 (DR4) and death receptor 5 (DR5) protein in a concentration- and time-dependent manner. The knockdown of DR5 significantly suppressed TRAIL-induced cleavage of PARP, which was enhanced by LCB. Treatment with an extracellular-regulated kinase (ERK) inhibitor (PD98059) or c-Jun N-terminal kinase (JNK) inhibitor (SP600125) markedly reduced the LCB-induced upregulation of DR5 expression and attenuated LCB-mediated TRAIL sensitization. In summary, LCB exhibits cytotoxic activity through modulation of the Akt/mTOR, ER stress and MAPK pathways in HCC cells and effectively enhances TRAIL sensitivity through the upregulation of DR5 expression in ERK- and JNK-dependent manner. Combination therapy with LCB and TRAIL may be an alternative treatment strategy for HCC.

A holistic assessment of spatiotemporal variation, driving factors, and risks influencing river water quality in the northeastern Qinghai-Tibet Plateau.

The Qinghai-Tibet Plateau (QTP) is the source for many of the most important rivers in Asia. It is also an essential ecological barrier in China and has the characteristic of regional water conservation. Given this importance, we analyzed the spatiotemporal distribution patterns and trends of 10 water quality parameters. These measurements were taken monthly from 67 monitoring stations in the northeastern QTP from 2015 to 2019. To evaluate water quality trends, major factors influencing water quality, and water quality risks, we used a series of analytical approaches including Mann-Kendall test, Boruta algorithm, and interval fuzzy number-based set-pair analysis (IFN-SPA). The results revealed that almost all water monitoring stations in the northeastern QTP were alkaline. From 2015 to 2019, the water temperature and dissolved oxygen of most monitoring stations were significantly reduced. Chemical oxygen demand, permanganate index, five-day biochemical oxygen demand, total phosphorus, and fluoride all showed a downward trend across this same time frame. The annual average total nitrogen (TN) concentration fluctuation did not significantly decrease across the measured time frame. Water quality index (WQI-DET) indicated bad or poor water quality in the study area; however, water quality index without TN (WQI-DET') reversed the water quality value. The difference between the two indexes suggested that TN was a significant parameter affecting river water quality in the northeastern QTP. Both Spearman correlation and Boruta algorithm show that elevation, urban land, cropland, temperature, and precipitation influence the overall water quality status in the northeastern QTP. The results showed that between 2015 and 2019, most rivers monitored had a relatively low risk of degradation in water quality. This study provides a new perspective on river water quality management, pollutant control, and risk assessment in an area like the QTP that has sensitive and fragile ecology.

Mechanisms and influencing factors of yttrium sorption on paddy soil: Experiments and modeling.

High-technology rare earth elements (REEs) as emerging contaminants have potentially hazardous risks for human health and the environment. Investigating the sorption of REEs on soils is crucial for understanding their migration and transformation. This study evaluated the sorption mechanisms and influencing factors of the rare earth element yttrium (Y) on paddy soil via integrated batch sorption experiments and theoretical modeling analysis. Site energy distribution theory (SEDT) combined with kinetics, thermodynamics, and isotherm sorption models were applied to illustrate the sorption mechanism. In addition, the effects of phosphorus (P), solution pH, particle size of soil microaggregates, and initial Y content on the sorption processes were evaluated by self-organizing map (SOM) and Boruta algorithm. The sorption kinetic behavior of Y on paddy soil was more consistent with the pseudo-second-order model. Thermodynamic results showed that the Y sorption was a spontaneous endothermic reaction. The generalized Langmuir model well described the isotherm data of Y sorption on heterogeneous paddy soil and soil microaggregates surface. The maximum sorption capacity of Y decreased with increasing soil particle size, which may be related to the number of sorption sites for Y on paddy soil and soil microaggregates, as confirmed by SEDT. The heterogeneity of sorption site energy for Y was the highest in the original paddy soil compared with the separated soil microaggregates. The SOM technique and Boruta algorithm highlighted that the initial concentration of Y and coexisting phosphorus played essential roles in the sorption process of Y, indicating that the addition of phosphate fertilizer may be an effective way to reduce the Y bioavailability in paddy soil in practice. These results can provide a scientific basis for the sustainable management of soil REEs and a theoretical foundation for the remediation of REEs-contaminated soils.

Gender-specific effects of prenatal mixed exposure to serum phthalates on neurodevelopment of children aged 2-3 years:the Guangxi Birth Cohort Study.

Phthalates have been shown to have adverse effects on neurodevelopment, which may be gender-specific. However, the association between prenatal mixed exposure to phthalates and children's neurodevelopment remains inconsistent. We measured 15 prenatal serum phthalate levels and evaluated children's neurodevelopmental indicators using Gesell Developmental Schedule (GDS) (n = 750). Generalized linear regression was fitted to examine the association. Among boys, mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) had adverse effects on gross motor [odds ratio (OR): 7.38, 95% confidence interval (CI):1.42, 38.46]. For gross motor in boys, joint effect was discovered between mono-2-ethylhexyl phthalate (MEHP) and MEHHP. Moreover, synergistic effects were found for MEHP with vanadium and cadmium, and antagonistic effects for MEHP with magnesium, calcium, titanium, iron, copper, selenium, rubidium, and strontium. We did not find statistically significant relationships in girls. In the 1st trimester, adverse effects were identified between mono-2-ethyl-5-oxoyhexyl phthalate (MEOHP) and adaptation (P = 0.024), and monomethyl phthalate (MMP) with social area (P = 0.017). In the 2nd trimester, MEHHP had adverse effects on social area (P = 0.035). In summary, we found boys may be more vulnerable to the neurotoxicity than girls in gross motor, and we also discovered the detrimental effects of phthalates on children's neurodevelopment in the 1st and 2nd trimesters. Therefore, the supplementation of appropriate elements in the 1st and 2nd trimesters may help reduce the adverse effects of phthalates on children's neurodevelopment, especially among boys.

Salidroside Ameliorates Ischemia-Induced Neuronal Injury through AMPK Dependent and Independent Pathways to Maintain Mitochondrial Quality Control.

Salidroside, an active ingredient in Rhodiola rosea, has potent protective activity against cerebral ischemia. However, the mechanisms underlying its pharmacological actions are poorly understood. In this study, we employed a mouse middle cerebral artery occlusion (MCAO) and cellular oxygen and glucose deprivation (OGD) models to test the hypothesis that salidroside may restore mitochondrial quality control in neurons by modulating the relevant signaling. The results indicated that salidroside mitigated almost 40% the ischemia-induced brain infarct volumes in mice and the OGD-decreased viability of neurons to ameliorate the mitochondrial functions. Furthermore, salidroside treatment alleviated the OGD- or ischemia-induced imbalance of mitochondrial fission and fusion, mitophagy and promoted mitochondrial biogenesis in neurons by attenuating the AMPK activity. Moreover, salidroside alleviated 50% the OGD-promoted mitochondrial calcium fluorescence intensity and 5% mitochondria-associated membrane (MAM) area by down-regulating GRP75 expression independent of the AMPK signaling. Finally, similar findings were achieved in primary mouse neurons. Collectively, these data indicate that salidroside effectively restores the mitochondria dynamics, facilitates mitochondrial biogenesis by attenuating the AMPK signaling, and maintains calcium homeostasis in neurons independent of the AMPK activity.

A Novel Selenium Polysaccharide Alleviates the Manganese (Mn)-Induced Toxicity in Hep G2 Cells and Caenorhabditis elegans.

Manganese (Mn) is now known to have a variety of toxicities, particularly when exposed to it in the workplace. However, there are still ineffective methods for reducing Mn's hazardous effects. In this study, a new selenium polysaccharide (Se-PCS) was developed from the shell of Camellia oleifera to reduce Mn toxicity in vitro and in vivo. The results revealed that Se-PCS may boost cell survival in Hep G2 cells exposed to Mn and activate antioxidant enzyme activity, lowering ROS and cell apoptosis. Furthermore, after being treated with Se-PCS, Caenorhabditis elegans survived longer under Mn stress. daf-16, a tolerant critical gene, was turned on. Moreover, the antioxidant system was enhanced as the increase in strong antioxidant enzyme activity and high expression of the sod-3, ctl-2, and gst-1 genes. A variety of mutations were also used to confirm that Se-PCS downregulated the insulin signaling pathway. These findings showed that Se-PCS protected Hep G2 cells and C. elegans via the insulin/IGF-1 signaling pathway and that it could be developed into a promising medication to treat Mn toxicity.

Modified Simiaowan prevents articular cartilage injury in experimental gouty arthritis by negative regulation of STAT3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Simiaowan (MSW) is a traditional Chinese medicine formula that is composed of six herbs. It has been widely used in the treatment of gouty arthritis. AIM OF THE STUDY: This study was designed to investigate the effect of MSW on gouty arthritis and explore the possible mechanisms. MATERIAL AND METHODS: The rat gouty arthritis model was established by intra-articular injection of Monosodium Urate (MSU) crystal, and then treated with MSW for 5 days. The perimeter of the knee joints was measured in a time-dependent manner and serum samples were collected for the detection of TNF-α, IL-1ß, and IL-6 protein levels by ELISA. The protein expressions of MMP-3, TIMP-3, STAT3, and p-STAT3 in cartilage tissues and C28/I2 cells were detected by Western blot, and the levels of proteoglycan in primary chondrocytes and cartilage tissues were determined by toluidine blue staining. In addition, AG490 and IL-6 were used in vitro to explore the function of IL-6/STAT3 pathway in the protective effect of MSU. RESULTS: MSW reduced the joint swelling rate in gouty arthritis model and inhibited MSU induced up-regulation of IL-1ß, TNF-α, and IL-6 protein levels in serum and synovial fluid. IL-1ß induced an increase in p-STAT3 and MMP-3 protein expression in C28/I2 cells, as well as a decrease in TIMP-3. MSW serum inhibited the protein expression changes induced by IL-1ß in vitro. Furthermore, inhibition of STAT3 signaling negated the effect of MSW serum on p-STAT3, MMP-3, and TIMP-3 protein levels in C28/I2 cells. MSW also increased the content of proteoglycan significantly both in vivo and in vitro. CONCLUSION: Our data indicated that MSW protected rats from MSU-induced experimental gouty arthritis and IL-1ß/IL-6/STAT3 pathway played an essential role in the protective effect of MSU against GA.

Study on the related factors of post-herpetic neuralgia in hospitalized patients with herpes zoster in Sichuan Hospital of Traditional Chinese Medicine based on big data analysis.

Although various factors were reported to be related to post-herpetic neuralgia (PHN), studies based on adequate and comprehensive data were absent. Data was extracted from cases of hospitalized patients with herpes zoster in dermatology department, Sichuan hospital of traditional Chinese medicine range from December, 2011 to February, 2018, and then cleaned to build prediction model with TREENET algorithms. Following evaluated the prediction model by ROC and confusion matrix, variables importance ranking and variables dependency analysis were performed, resulting in the importance ranking of factors for PHN and the dependency between factors and PHN. Based on strict inclusion and exclusion criteria, 1303 (571 PHN and 732 normal controls) cases and 2958 indicators were selected. Model evaluation showed high ROC value (training sample = 0.985, test samples = 0.752) and high accuracy value (70.27%), which indicated that the model was predictive. After variables importance ranking and variables dependency analysis, 62 variables in the model were associated with the occurrence of PHN. Our study identified 62 variables related to PHN and revealed that various variables were the important risk factors for PHN, including age, MCHC, sodium and UA.

Optimization of reduced chemical fertilizer use in tea gardens based on the assessment of related environmental and economic benefits.

Chemical fertilizer application is the primary method used to maintain tea yield and quality, but has a negative environmental impact owing to its excessive use. This study sought to assess the environmental and economic benefits of three different chemical fertilizer reduction modes: Single reduction of chemical fertilizer (SRCF), combined application of organic and chemical fertilizer (CAOF), and controlled-release fertilizer substitute (CRFS). Differences in soil nutrient content, NP (NH4+-N, NO3-N and total P) runoff loss, tea yield and quality, and the revenue of tea planting across different fertilizer reduction treatments were then discussed. We also analyzed the coupling effects of these different fertilization modes, fertilization rate and time on soil NP runoff loss, which allowed us to determine the optimum fertilization method based on differences in their respective environmental and economic benefits. Our results revealed differences in soil nutrient content, tea yield and quality, NP runoff loss, and revenue owing to tea planting across the different fertilization treatments. Soil pH after fertilization was significantly lower than before fertilization. CAOF was beneficial and improved soil nutrients as well as tea yield and quality. Of the tested methods, 50% combined application of organic and chemical fertilizer (CAOF2) was the best, as it resulted in the best tea quality and yield. CAOF2 also had the highest revenue. In addition, it was beneficial in reducing NP runoff loss. CRFS was advantageous in its persistent fertilizer efficiency and reduction in NP runoff loss. With CAOF, NP runoff loss was primarily caused by quick-acting chemical fertilizer. With extended time, NP runoff loss caused by fertilization was gradually decreased. Given our analysis of the environmental and economic benefits of different fertilizer reduction methods, CAOF2 emerged in this study as the best fertilizer reduction treatment option.