Zhen-Wu-Tang ameliorates lupus nephritis by diminishing renal tissue-resident memory CD8+ T cells via suppressing IL-15/STAT3 pathway.

Zhen-Wu-Tang (ZWT), a conventional herbal mixture, has been recommended for treating lupus nephritis (LN) in clinic. However, its mechanisms of action remain unknown. Here we aimed to define the immunological mechanisms underlying the effects of ZWT on LN and to determine whether it affects renal tissue-resident memory T (TRM) cells. Murine LN was induced by a single injection of pristane, while in vitro TRM cells differentiated with IL-15/TGF-ß. We found that ZWT or mycophenolate mofetil treatment significantly ameliorated kidney injury in LN mice by decreasing 24-h urine protein, Scr and anti-dsDNA Ab. ZWT also improved renal pathology and decreased IgG and C3 depositions. In addition, ZWT down-regulated renal Desmin expression. Moreover, it lowered the numbers of CD8+ TRM cells in kidney of mice with LN while decreasing their expression of TNF-α and IFN-γ. Consistent with in vivo results, ZWT-containing serum inhibited TRM cell differentiation induced by IL-15/TGF-ß in vitro. Mechanistically, it suppressed phosphorylation of STAT3 and CD122 （IL2/IL-15Rß）expression in CD8+ TRM cells. Importantly, ZWT reduced the number of total F4/80+CD11b+ and CD86+, but not CD206+, macrophages in the kidney of LN mice. Interestingly, ZWT suppressed IL-15 protein expression in macrophages in vivo and in vitro. Thus, we have provided the first evidence that ZWT decoction can be used to improve the outcome of LN by reducing CD8+ TRM cells via inhibition of IL-15/IL-15R /STAT3 signaling.

Salvianolic acid B attenuates membranous nephropathy by activating renal autophagy via microRNA-145-5p/phosphatidylinositol 3-kinase/AKT pathway.

The abnormal proliferation and inflammatory response of the mesangial cells play a crucial role in the progression of membranous nephropathy (MN). Herein, this study aimed to investigate the therapeutic effect of Salvianolic acid B (SalB) on MN-induced mesangial abnormalities and its underlying mechanisms. MN models were established in cationic bovine serum albumin-induced Sprague-Dawley rats and lipopolysaccharide-induced human mesangial cells (HMCs). Following SalB and microRNA-145-5p antagomir treatment, kidney function was investigated by 24-hours urine protein, serum creatinine, and blood urea nitrogen. Pathological changes of kidney were investigated by Periodic acid Schiff staining. CD68 and IgG were detected by immunofluorescence in glomerulus. Mesangial autophagosomes were observed by transmission electron microscope. MicroRNA-145-5p inhibitor, mimic, LY294002, and SalB were used to treat with HMCs. In kidney and HMCs, IL-1 ß, IL-2, IL-6, TNF-α and microRNA-145-5p was detected by quantitative real-time PCR. Phosphatidylinositol 3-kinase (PI3K), phosphorylated AKT, AKT, beclin1, and microtubule-associated protein light chain 3 (LC3) levels were detected by Western blot. HMCs proliferation and cycle were detected by Cell Counting Kit-8 and flow cytometry. LC3 were detected by LC3-dual-fluorescent adenovirus in HMCs. Our results showed that SalB significantly ameliorated kidney function and pathological changes. Furthermore, it significantly alleviated proliferation, inflammation and activated autophagy in mesangial cells. Moreover, microRNA-145-5p antagomir accentuated MN while microRNA-145-5p inhibitor and LY294002 encouraged proliferation and inflammation through PI3K/AKT pathway in HMCs. Collectively, our study demonstrated that SalB activated renal autophagy to reduce cell proliferation and inflammation of MN, which was mediated by microRNA-145-5p to inhibit PI3K/AKT pathway, and ultimately attenuated MN.

Human hand as a powerless and multiplexed infrared light source for information decryption and complex signal generation.

With the increasing pursuit of intelligent systems, the integration of human components into functional systems provides a promising route to the ultimate human-compatible intelligent systems. In this work, we explored the integration of the human hand as the powerless and multiplexed infrared (IR) light source in different functional systems. With the spontaneous IR radiation, the human hand provides a different option as an IR light source. Compared to engineered IR light sources, the human hand brings sustainability with no need of external power and also additional level of controllability to the functional systems. Besides the whole hand, each finger of the hand can also independently provide IR radiation, and the IR radiation from each finger can be selectively diffracted by specific gratings, which helps the hand serve as a multiplexed IR light source. Considering these advantages, we show that the human hand can be integrated into various engineered functional systems. The integration of hand in an encryption/decryption system enables both unclonable and multilevel information encryption/decryption. We also demonstrate the use of the hand in complex signal generation systems and its potential application in sign language recognition, which shows a simplified recognition process with a high level of accuracy and robustness. The use of the human hand as the IR light source provides an alternative sustainable solution that will not only reduce the power used but also help move forward the effort in the integration of human components into functional systems to increase the level of intelligence and achieve ultimate control of these systems.

Key indexes and the emerging tool for tumor microenvironment editing.

Many cancer management approaches including immunotherapies can not achieve desirable therapeutic efficacies if targeting tumors alone or could not effectively reach tumor cells. The concept of tumor microenvironment and its induced gene reprogramming have largely extended our current understandings on the determinants of tumor initiation/progression and fostered our hope in establishing first-line therapies targeting cancer microenvironment or adjuvant therapies enhancing the efficacies of existing oncotherapeutic modalities such as immunotherapies for efficient cancer management. This review identifies key indexes of tumor microenvironment, i.e., hypoxia, acidosis, hypo-nutrition and inflammation, which collectively determine the feature and the fate of adjacent tumor cells, and proposes cold atmospheric plasma, the fourth state of matter that is largely composed of various reactive oxygen and nitrogen species, as a promising tool for tumor microenvironment editing. We propose that cold atmospheric plasma represents an emerging onco-therapeutic strategy alone or complementing existing treatment approaches given its multi-modal nature through tumor microenvironment modulation.

Patterned Surfaces for Solar-Driven Interfacial Evaporation.

Solar-driven interfacial evaporation, as one of the most effective ways to convert and utilize solar energy, has attracted lot of interest recently. Most of the previous research studies, however, mainly focused on nonpatterned solar absorbers by improving the structural and chemical characteristics of the solar absorbers used in the interfacial evaporation systems. In this work, we investigated the influence of patterned surface on the evaporation performance of solar absorbers. The patterned surfaces studied, which include black patterns and white patterns, were achieved by selectively printing carbon black on the air-laid paper. Such a design leads to the lateral temperature differences between adjacent patterns of the solar absorber under solar illumination. The temperature differences result in the lateral heat and mass transfer between those patterns, which can effectively accelerate solar-driven vapor generation. With similar patterns and same coverage of carbon black, the increase in the circumference of the surface patterns leads to the increase in the evaporation performance. Additionally, we found that the evaporation performance can be optimized through the design of surface patterns, which demonstrates the potential in reducing the usage of the light-absorbing materials in the solar absorber. The findings in this work not only expand the understanding of the interfacial evaporation systems but also offer additional guidelines in designing interfacial evaporation systems.

[Risk factors analysis and security application discussion of Polygonum multiflorum based on retrospective study].

In recent years，hepatotoxicity problem of Polygonum multiflorum has caused high attention. Domestic scholars also explored the causes of liver damage caused by it. For example, the establishment of guideline for diagnosis and treatment of herb-induced liver injury, and the theory about relationship between hepatocyte toxicity and chemical composition, solvents, processing, use and pathological basis of patients and so on. To try to combine theory with practice，author analyzed risk factors about the case reports of P. multiflorum causing liver damage, and made some suggestions on P. multiflorum about individualized application, drug selection and requirements for taking. This for providing reference for the safe use of P. multiflorum.

Sodium P-aminosalicylic acid inhibits sub-chronic manganese-induced neuroinflammation in rats by modulating MAPK and COX-2.

Excessive manganese (Mn) accumulation in the brain may induce an extrapyramidal disorder known as manganism. Inflammatory processes play a critical role in neurodegenerative diseases. Therapeutically, non-steroidal anti-inflammatory drugs or analogous anti-inflammatory therapies have neuroprotective effects. As a non-steroidal anti-inflammatory drug, p-aminosalicylic acid (PAS) has anti-inflammatory effects, which are mediated by decreased prostaglandins E2 (PGE2) levels. The aim of the current study was to investigate whether PAS-Na treatment prevents Mn-induced behavioral changes and neuroinflammation in vivo. Male Sprague-Dawley rats were intraperitoneally (i.p.) injected with MnCl2·4H2O (15mg/kg) for 12 weeks, followed by 6 weeks PAS-Na treatment. Sub-chronic Mn exposure increased Mn levels in the whole blood, cortex, hippocampus and thalamus, and induced learning and memory deficits, concomitant with astrocytes activation in the cortex, hippocampus and thalamus. Moreover inflammatory cytokine levels in serum and brain of Mn-treated group were increased, including IL-1ß, IL-6, TNF-αand PGE2, especially in the hippocampus and thalamus. Furthermore, sub-chronic Mn exposure also increased inflammatory cytokines and COX-2 in transcription levels concomitant with increased MAPK signaling and COX-2 in the same selected brain regions. PAS-Na treatment at the highest doses also decreased Mn levels in the whole blood and selected brain tissues, and reversed the Mn-induced learning and memory deficits. PAS-Na inhibited astrocyte activation as well as the Mn-induced increase in inflammatory cytokine levels, reducing p38, ERK MAPK pathway and COX-2 activity. In contrast PAS-Na had no effects on the JNK MAPK pathway. These data establish the efficacy of PAS-Na not only as a chelating agent to mobilize whole blood Mn, but also as an anti-inflammatory agent.

Sodium p-Aminosalicylic Acid Reverses Sub-Chronic Manganese-Induced Impairments of Spatial Learning and Memory Abilities in Rats, but Fails to Restore γ-Aminobutyric Acid Levels.

Excessive manganese (Mn) exposure is not only a health risk for occupational workers, but also for the general population. Sodium para-aminosalicylic acid (PAS-Na) has been successfully used in the treatment of manganism, but the involved molecular mechanisms have yet to be determined. The present study aimed to investigate the effects of PAS-Na on sub-chronic Mn exposure-induced impairments of spatial learning and memory, and determine the possible involvements of γ-aminobutyric acid (GABA) metabolism in vivo. Sprague-Dawley male rats received daily intraperitoneal injections MnCl2 (as 6.55 mg/kg Mn body weight, five days per week for 12 weeks), followed by daily subcutaneous injections of 100, 200, or 300 mg/kg PAS-Na for an additional six weeks. Mn exposure significantly impaired spatial learning and memory ability, as noted in the Morris water maze test, and the following PAS-Na treatment successfully restored these adverse effects to levels indistinguishable from controls. Unexpectedly, PAS-Na failed to recover the Mn-induced decrease in the overall GABA levels, although PAS-Na treatment reversed Mn-induced alterations in the enzyme activities directly responsible for the synthesis and degradation of GABA (glutamate decarboxylase and GABA-transaminase, respectively). Moreover, Mn exposure caused an increase of GABA transporter 1 (GAT-1) and decrease of GABA A receptor (GABAA) in transcriptional levels, which could be reverted by the highest dose of 300 mg/kg PAS-Na treatment. In conclusion, the GABA metabolism was interrupted by sub-chronic Mn exposure. However, the PAS-Na treatment mediated protection from sub-chronic Mn exposure-induced neurotoxicity, which may not be dependent on the GABA metabolism.

Sodium P-Aminosalicylic Acid Improved Manganese-Induced Learning and Memory Dysfunction via Restoring the Ultrastructural Alterations and γ-Aminobutyric Acid Metabolism Imbalance in the Basal Ganglia.

Excessive intake of manganese (Mn) may cause neurotoxicity. Sodium para-aminosalicylic acid (PAS-Na) has been used successfully in the treatment of Mn-induced neurotoxicity. The γ-aminobutyric acid (GABA) is related with learning and memory abilities. However, the mechanism of PAS-Na on improving Mn-induced behavioral deficits is unclear. The current study was aimed to investigate the effects of PAS-Na on Mn-induced behavioral deficits and the involvement of ultrastructural alterations and γ-aminobutyric acid (GABA) metabolism in the basal ganglia of rats. Sprague-Dawley rats received daily intraperitoneally injections of 15 mg/kg MnCl2.4H2O, 5d/week for 4 weeks, followed by a daily back subcutaneously (sc.) dose of PAS-Na (100 and 200 mg/kg), 5 days/week for another 3 or 6 weeks. Mn exposure for 4 weeks and then ceased Mn exposure for 3 or 6 weeks impaired spatial learning and memory abilities, and these effects were long-lasting. Moreover, Mn exposure caused ultrastructural alterations in the basal ganglia expressed as swollen neuronal with increasing the electron density in the protrusions structure and fuzzed the interval of neuropil, together with swollen, focal hyperplasia, and hypertrophy of astrocytes. Additionally, the results also indicated that Mn exposure increased Glu/GABA values as by feedback loops controlling GAT-1, GABAA mRNA and GABAA protein expression through decreasing GABA transporter 1(GAT-1) and GABA A receptor (GABAA) mRNA expression, and increasing GABAA protein expression in the basal ganglia. But Mn exposure had no effects on GAT-1 protein expression. PAS-Na treatment for 3 or 6 weeks effectively restored the above-mentioned adverse effects induced by Mn. In conclusion, these findings suggest the involvement of GABA metabolism and ultrastructural alterations of basal ganglia in PAS-Na's protective effects on the spatial learning and memory abilities.

Sodium para-aminosalicylate protected cultured basal ganglia astrocytes from manganese-induced DNA damages and alteration of amino acid neurotransmitter levels.

Sodium para-aminosalicylate (PAS-Na) was first applied successfully in clinical treatment of two manganism patients with good prognosis. However, the mechanism of how PAS-Na protects against Mn-induced neurotoxicity is still elusive. The current study was conducted to explore the effects of PAS-Na on Mn-induced basal ganglia astrocyte injury, and the involvement of amino acid neurotransmitter in vitro. Basal ganglia astrocytes were exposed to 500 µM manganese chloride (MnCl2) for 24 hr, following by 50, 150, or 450 µM PAS-Na treatment for another 24 hr. MnCl2 significantly decreased viability of astrocytes and induced DNA damages via increasing the percentage of tail DNA and Olive tail moment of DNA. Moreover, Mn interrupted amino acid neurotransmitters by decreasing Gln levels and increasing Glu, Gly levels. In contrast, PAS-Na treatment reversed the aforementioned Mn-induced toxic effects on basal ganglia astrocytes. Taken together, our results demonstrated that excessive Mn exposure may induce toxic effects on basal ganglia astrocytes, while PAS-Na could protect basal ganglia astrocytes from Mn-induced neurotoxicity.

The influence of manganese treatment on the distribution of metal elements in rats and the protection by sodium para-amino salicylic acid.

Manganese (Mn) overexposure induced neurological damages, which could be potentially protected by sodium para-aminosalicylic acid (PAS-Na). In this study, we systematically detected the changes of divalent metal elements in most of the organs and analyzed the distribution of the metals in Mn-exposed rats and the protection by PAS-Na. Sprague Dawley (SD) rats received intraperitoneal injections of 15mg/kg MnCl2·4H2O (5d/week for 3 weeks), followed by subcutaneous (back) injections of PAS-Na (100 and 200mg/kg, everyday for 5 weeks). The concentrations of Mn and other metal elements [Iron (Fe), Copper (Cu), Zinc (Zn), Magnesium (Mg), Calcium (Ca)] in major organs (liver, spleen, kidney, thighbone and iliac bone, cerebral cortex, hippocampus and testes) and blood by Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). The results showed that Mn overexposure significantly increased Mn in most organs, Fe and Zn in liver, Fe and Mg in blood; however decreased Fe, Cu, Zn, Mg and Ca in cortex, Cu and Zn in kidney, Cu and Mg in iliac bone, and Zn in blood. In contrast, PAS-Na treatment restored most changes particularly in cortex. In conclusion, excessive Mn exposure disturbed the balance of other metal elements but PAS-Na post-treatments could restore these alterations.

Sodium Para-aminosalicylic Acid Protected Primary Cultured Basal Ganglia Neurons of Rat from Manganese-Induced Oxidative Impairment and Changes of Amino Acid Neurotransmitters.

Manganese (Mn), an essential trace metal for protein synthesis and particularly neurotransmitter metabolism, preferentially accumulates in basal ganglia. However, excessive Mn accumulation may cause neurotoxicity referred to as manganism. Sodium para-aminosalicylic acid (PAS-Na) has been used to treat manganism with unclear molecular mechanisms. Thus, we aim to explore whether PAS-Na can inhibit Mn-induced neuronal injury in basal ganglia in vitro. We exposed basal ganglia neurons with 50 µM manganese chloride (MnCl2) for 24 h and then replaced with 50, 150, and 450 µM PAS-Na treatment for another 24 h. MnCl2 significantly decreased cell viability but increased leakage rate of lactate dehydrogenase and DNA damage (as shown by increasing percentage of DNA tail and Olive tail moment). Mechanically, Mn reduced glutathione peroxidase and catalase activity and interrupted amino acid neurotransmitter balance. However, PAS-Na treatment reversed the aforementioned Mn-induced toxic effects. Taken together, these results showed that PAS-Na could protect basal ganglia neurons from Mn-induced neurotoxicity.

[Summary and analysis of safety warning on clinical application of anti-cold Chinese patent medicine preparations].

In China, many surveys have shown that most people do not have a correct understanding about cold and administration of anti-cold Chinese patent medicine preparations. The author conducted a systematic summary and analysis on the actual application of anti-cold Chinese patent medicine preparations as well as the warning on safe application of anti-cold Chinese patent medicine preparations in Clinical Medication Information of China Pharmacopoeia, in the expectation of reducing the blind application of anti-cold Chinese patent medicine preparations and providing traditional Chinese medicine pharmacists new ideas in monitoring the safe application of exterior syndrome-relieving Chinese patent medicine preparations.

[Study on microwave processing technology of achyranthis bidentatae radix by orthogonal design].

OBJECTIVE: To study the microwave processing method of Achyranthis Bidentatae Radix processed with wine. METHODS: The content of total saponins, oleanolic acid and ß-ecdysterone were determined as the indices to get the optimal microwave processing technology by orthogonal design. RESULTS: The best technology of Achyranthis Bidentatae Radix processed with wine were:the amount of vinegar was 20%, moistening time was 60 min, with 60% microwave heating for 3 min. CONCLUSION: This method is simple, practical, scientific and easy to control.