[Chaihu Sanshen Capsules protect rats from myocardial ischemia reperfusion injury via PKCßâ ¡/NOX2/ROS signaling pathway].

This study aims to explore the pathogenesis of myocardial ischaemia reperfusion injury(MIRI) based on oxidative stress-mediated programmed cell death and the mechanism and targets of Chaihu Sanshen Capsules in treating MIRI via the protein kinase Cß(PKCßⅡ)/NADPH oxidase 2(NOX2)/reactive oxygen species(ROS) signaling pathway. The rat model of MIRI was established by the ligation of the left anterior descending branch. Rats were randomized into 6 groups: sham group, model group, clinically equivalent-, high-dose Chaihu Sanshen Capsules groups, N-acetylcysteine group, and CGP53353 group. After drug administration for 7 consecutive days, the area of myocardial infarction in each group was measured. The pathological morphology of the myocardial tissue was observed by hematoxylin-eosin(HE) staining. The apoptosis in the myocardial tissue was observed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL). Enzyme-linked immunosorbent assay(ELISA) was employed to measure the le-vels of indicators of myocardial injury and oxidative stress. The level of ROS was detected by flow cytometry. The protein and mRNA levels of the related proteins in the myocardial tissue were determined by Western blot and real-time quantitative PCR(RT-qPCR), respectively. Compared with the sham group, the model group showed obvious myocardial infarction, myocardial structural disorders, interstitial edema and hemorrhage, presence of a large number of vacuoles, elevated levels of myocardial injury markers, myocardial apoptosis, ROS, and malondialdehyde(MDA), lowered superoxide dismutase(SOD) level, and up-regulated protein and mRNA le-vels of PKCßⅡ, NOX2, cysteinyl aspartate specific proteinase-3(caspase-3), and acyl-CoA synthetase long-chain family member 4(ACSL4) in the myocardial tissue. Compared with the model group, Chaihu Sanshen Capsules reduced the area of myocardial infarction, alleviated the pathological changes in the myocardial tissue, lowered the levels of myocardial injury and oxidative stress indicators and apoptosis, and down-regulated the mRNA and protein levels of PKCßⅡ, NOX2, caspase-3, and ACSL4 in the myocardial tissue. Chaihu Sanshen Capsules can inhibit oxidative stress and programmed cell death(apoptosis, ferroptosis) by regulating the PKCßⅡ/NOX2/ROS signaling pathway, thus mitigating myocardial ischemia reperfusion injury.

Advancements in the research of immune checkpoint inhibitors for the treatment of advanced esophageal squamous cell carcinoma.

Esophageal cancer (EC) has a high mortality rate and poor prognosis. Most patients are diagnosed at an advanced stage or with distant metastasis, making surgery impossible. Traditional curative radiotherapy and chemotherapy have limited efficacy. In recent years, with the development of clinical trials, immune checkpoint inhibitors (ICIs) have shown promising results in treating advanced and metastatic esophageal squamous cell carcinoma (ESCC) patients. ICIs have gradually become a primary therapeutic approach for EC. This review summarizes and provides an overview of the current research status and progress of ICIs in the treatment of advanced ESCC patients.

Green investing in China's air cargo industry: Opportunities and challenges for sustainable transportation.

Aviation cargo remains vital in the economic activities to transported goods from one place to another. The developed and developing countries mainly consider the transaction routes for air transportation for safe and quickest mode. Chinese economy is attracting the global World through its exports. The country's air cargo system is mainly reliant on gasoline and petroleum-based fuels, which harms the country's green transportation agenda. The high use of fuel combustions in the aviation sector needed greenfield investment that helps to use green energy as an alternative sustainable fuel. Further, sustainable aviation insurance and financial coverage are needed to mitigate the adverse negative externalities from air cargo operations. Based on the crucial facts, the study used air cargo operations, transportation fuel combustions, private investment in the transportation and insurance coverage in the pollution damage function for the China economy using data from 1975 to 2020. The research employed a non-linear ARDL Bounds testing strategy to break down the sequence of variables into dynamic positive and negative multipliers. Positive shocks in air freight, insurance services, and greenfield investment have been shown to reduce carbon emissions immediately and over the long term. In the short term, carbon damages are exacerbated by the negative shocks resulting from the use of transportation fuel and the availability of insurance. Moreover, both the positive and negative shocks associated with transportation fuel combustions and air transportation freights contribute to a rise in carbon damage. The variance decomposition analysis validated the asymmetric correlations between the aforementioned variables in the intertemporal environment. Based on the findings, negative shocks from total fuel combustions are expected to impose the greatest carbon damages over the next decade, followed by insurance services and air freight operations. The study concludes that air cargo operations need to be sustainable transacting routes fueled by biofuel energy sources, greenfield investment, and sustainable aviation insurance coverage to achieve the 'green is clean' transportation agenda.

Ethyl 2-[(tert-but-oxy-carbon-yl)amino]-thia-zole-5-carboxyl-ate.

In the crystal of the title compound, C(11)H(16)N(2)O(4)S, molecules are linked via pairs of N-H⋯N hydrogen bonds to form inversion dimers. The dimers are linked by a weak C-H⋯O interaction to form chains propagating along direction [100].

Chai-Hu-San-Shen Capsule Ameliorates Ventricular Arrhythmia Through Inhibition of the CaMKII/FKBP12.6/RyR2/Ca2+ Signaling Pathway in Rats with Myocardial Ischemia.

Ventricular arrhythmia is one of the main causes of sudden cardiac death, especially after myocardial ischemia. Previous studies have shown that Chai-Hu-San-Shen capsule (CHSSC) can reduce the incidence of ventricular arrhythmias following myocardial ischemia, however, the mechanisms of it are unclear. In present study, we explored the mechanism of CHSSC ameliorates ventricular arrhythmia following myocardial ischemia via inhibiting the CaMKII/FKBP12.6/RyR2/Ca2+ signaling pathway. In vivo, a myocardial ischemia rat model was established and treated with CHSSC to evaluate the therapeutic effect of CHSSC. In vitro, we established an ischemia model in H9C2 cells and treated with CHSSC, KN-93, or H-89. Then, intracellular Ca2+ content, the expression of RyR2, and the interaction between FKBP12.6 and RyR2 were detected. The results showed that CHSSC could delay the occurrence of ventricular arrhythmias and shorten the duration of ventricular arrhythmias. After myocardial ischemia, the intracellular Ca2+ content was increased, and CHSSC treatment mitigated this increase, down-regulated the levels of p-CaMKII, CaMKII, p-RyR2, and RyR2, and up-regulated the levels of p-RyR2 (Ser2808) and p-RyR2 (Ser2814). Co-immunoprecipitation showed an interaction between FKBP12.6 and RyR2, and CHSSC up-regulated the content of the FKBP12.6-RyR2 complex in ischemic cells. In conclusion, our study showed that CaMKII activation led to hyperphosphorylation of RyR2 (Ser2814) and RyR2 (Ser2808) during cardiomyocyte ischemia, which resulted in dissociation of the FKBP12.6-RyR2 complex, and increased intracellular Ca2+ content, which may contribute to the development of ventricular arrhythmias. CHSSC may reduce the incidence of ventricular arrhythmias following myocardial ischemia through inhibition of the CaMKII/RyR2/FKBP12.6/Ca2+ signaling pathway.

LncRNA SOX2-OTinhibitionprotects against myocardialischemia/reperfusion-inducedinjury via themicroRNA-186-5p (miR-186-5p)/Yin Yang 1 (YY1)pathway.

Long noncoding RNAs (lncRNAs) exert essential effects in regulating myocardial ischemia/reperfusion (MI/R)-induced injury. This work intended to explore the functions of lncRNA SOX2-OT and its regulatory mechanism within MI/R-induced injury. In this study, gene expression was determined by RT-qPCR. Western blotting was applied for the detection of protein levels. Pro-inflammatory cytokine concentrations, cardiomyocyte viability, and apoptosis were detected via ELISA, CCK-8 and flow cytometry. In the in vitro model, SOX2-OT and YY1 were both upregulated, while miR-186-5p was downregulated. SOX2-OT knockdown attenuated oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cardiomyocyte dysregulation through relieving inflammation, promoting proliferation, and reducing apoptosis in OGD/R-treated H2C9 cells. SOX2-OT positively regulated YY1 expression via miR-186-5p. Moreover, miR-186-5p inhibition or YY1 upregulation abolished the effects of SOX2-OT blocking on the inflammatory responses, proliferation, and apoptosis of OGD/R-challenged H2C9 cells. In conclusion, our results, for the first time, demonstrated that SOX2-OT inhibition attenuated MI/R injury in vitro via regulating the miR-186-5p/YY1 axis, offering potential therapeutic targets for MI/R injury treatment.

Real-time telemetry system for amperometric and potentiometric electrochemical sensors.

A real-time telemetry system, which consists of readout circuits, an analog-to-digital converter (ADC), a microcontroller unit (MCU), a graphical user interface (GUI), and a radio frequency (RF) transceiver, is proposed for amperometric and potentiometric electrochemical sensors. By integrating the proposed system with the electrochemical sensors, analyte detection can be conveniently performed. The data is displayed in real-time on a GUI and optionally uploaded to a database via the Internet, allowing it to be accessed remotely. An MCU was implemented using a field programmable gate array (FPGA) to filter noise, transmit data, and provide control over peripheral devices to reduce power consumption, which in sleep mode is 70 mW lower than in operating mode. The readout circuits, which were implemented in the TSMC 0.18-µm CMOS process, include a potentiostat and an instrumentation amplifier (IA). The measurement results show that the proposed potentiostat has a detectable current range of 1 nA to 100 µA, and linearity with an R2 value of 0.99998 in each measured current range. The proposed IA has a common-mode rejection ratio (CMRR) greater than 90 dB. The proposed system was integrated with a potentiometric pH sensor and an amperometric nitrite sensor for in vitro experiments. The proposed system has high linearity (an R2 value greater than 0.99 was obtained in each experiment), a small size of 5.6 cm × 8.7 cm, high portability, and high integration.

Formononetin exhibits anticancer activity in gastric carcinoma cell and regulating miR-542-5p.

Formononetin exhibits anti-neoplastic activities in specific types of cancers, such as colon carcinoma and breast cancer. Nevertheless, its role in suppressing gastric carcinoma (GC) growth and metastatic-associated phenotypes has not been fully understood. Here, we demonstrated that formononetin decreased the viability of GC cell line SGC-7901 and MGC-803. Furthermore, formononetin suppressed the migration and invasion abilities of GC cells. Consistent with the results in vitro, the anticancer effect of formononetin was verified using xenograft model. The expression of microRNA-542-5p (miR-542-5p), acted as an oncogene in many cancers, was identified to be upregulated in GC. Importantly, miR-542-5p might involve in formononetin exhibits anticancer activity in GC cells. Taken together, these results indicate that formononetin inhibits the growth and aggressiveness of GC cells in vitro and in vivo.

Wide dynamic range CMOS potentiostat for amperometric chemical sensor.

Presented is a single-ended potentiostat topology with a new interface connection between sensor electrodes and potentiostat circuit to avoid deviation of cell voltage and linearly convert the cell current into voltage signal. Additionally, due to the increased harmonic distortion quantity when detecting low-level sensor current, the performance of potentiostat linearity which causes the detectable current and dynamic range to be limited is relatively decreased. Thus, to alleviate these irregularities, a fully-differential potentiostat is designed with a wide output voltage swing compared to single-ended potentiostat. Two proposed potentiostats were implemented using TSMC 0.18-µm CMOS process for biomedical application. Measurement results show that the fully differential potentiostat performs relatively better in terms of linearity when measuring current from 500 pA to 10 uA. Besides, the dynamic range value can reach a value of 86 dB.

A Knowledge-Fusion Ranking System with an Attention Network for Making Assignment Recommendations.

In recent decades, more teachers are using question generators to provide students with online homework. Learning-to-rank (LTR) methods can partially rank questions to address the needs of individual students and reduce their study burden. Unfortunately, ranking questions for students is not trivial because of three main challenges: (1) discovering students' latent knowledge and cognitive level is difficult, (2) the content of quizzes can be totally different but the knowledge points of these quizzes may be inherently related, and (3) ranking models based on supervised, semisupervised, or reinforcement learning focus on the current assignment without considering past performance. In this work, we propose KFRank, a knowledge-fusion ranking model based on reinforcement learning, which considers both a student's assignment history and the relevance of quizzes with their knowledge points. First, we load students' assignment history, reorganize it using knowledge points, and calculate the effective features for ranking in terms of the relation between a student's knowledge cognitive and the question. Then, a similarity estimator is built to choose historical questions, and an attention neural network is used to calculate the attention value and update the current study state with knowledge fusion. Finally, a rank algorithm based on a Markov decision process is used to optimize the parameters. Extensive experiments were conducted on a real-life dataset spanning a year and we compared our model with the state-of-the-art ranking models (e.g., ListNET and LambdaMART) and reinforcement-learning methods (such as MDPRank). Based on top-k nDCG values, our model outperforms other methods for groups of average and weak students, whose study abilities are relatively poor and thus their behaviors are more difficult to predict.

Bu-Shen-Huo-Xue Decoction Ameliorates Diabetic Nephropathy by Inhibiting Rac1/PAK1/p38MAPK Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Mice.

Diabetic nephropathy (DN), a leading cause of end-stage renal disease, is associated with high morbidity and mortality rates worldwide and the development of new drugs to treat DN is urgently required. Bu-Shen-Huo-Xue (BSHX) decoction is a traditional Chinese herbal formula, made according to traditional Chinese medicine (TCM) theory, and has been used clinically to treat DN. In the present study, we established a high-fat diet/streptozotocin-induced diabetic mouse model and treated the mice with BSHX decoction to verify its therapeutic effects in vivo. Ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was applied to analyze the chemical composition and active compounds of BSHX decoction. Markers of podocyte epithelial-mesenchymal transition and the Rac1/PAK1/p38MAPK signaling pathway were evaluated to investigate the mechanism underlying function of BSHX decoction. BSHX decoction effectively alleviated diabetic symptoms, according to analysis of the renal function indicators, serum creatinine, blood urea nitrogen, serum uric acid, and urinary albumin excretion rate, as well as renal histopathology and ultrastructural pathology of DN mice. We identified 67 compounds, including 20 likely active compounds, in BSHX decoction. The podocyte markers, nephrin and podocin, were down-regulated, while the mesenchymal markers, α-SMA and FSP-1, were up-regulated in DN mouse kidney; however, the changes in these markers were reversed on treatment with BSHX decoction. GTP-Rac1 was markedly overexpressed in DN mice and its levels were significantly decreased in response to BSHX decoction. Similarly, levels of p-PAK1 and p-p38MAPK which indicate Rac1 activation, were reduced on treatment with BSHX decoction. Together, our data demonstrated that BSHX decoction ameliorated renal function and podocyte epithelial-mesenchymal transition via inhibiting Rac1/PAK1/p38MAPK signaling pathway in high-fat diet/streptozotocin-induced diabetic mice. Further, we generated a quality control standard and numerous potential active compounds from BSHX decoction for DN.

LncRNA-NR_033515 promotes proliferation, fibrogenesis and epithelial-to-mesenchymal transition by targeting miR-743b-5p in diabetic nephropathy.

Diabetic nephropathy (DN) is a crucial microvascular complication of diabetes. Long non-coding RNAs (lncRNAs) participate in the occurrence and development of various diseases, but the function and regular mechanism of lncRNA-NR_033515 in DN is still unclear. In the present study, we demonstrated that the expression of NR_033515 was significantly increased in the serum of DN patients and was related to the different stages of DN. NR_033515 was also positively associated with diagnostic markers of DN (KIM-1 and NGAL). Overexpression of NR_033515 promoted proliferation, and inhibited apoptosis of MMC cells and increased the expression levels of proliferation-related genes. NR_033515 also accelerated the expression levels of fibrogenesis-related genes. TGF-ß1 enhanced NR_033515-induced Epithelial-mesenchymal transition (EMT), while NR_033515 over-expression accelerated TGF-ß1-induced EMT. Furthermore, we found that NR_033515 promoted cell proliferation and regulated P38, ASK1, Fibronectin, α-SMA, E-cadherin, and Vimentin expressions by miR-743b-5p. Therefore, our data indicated the potential role of NR_033515 in the proliferation, fibrogenesis and EMT in DN. NR_033515 could be a pivotal potential diagnostic and therapeutic target for the treatment of DN.

MiR-663a/MiR-423-5p are involved in the pathogenesis of lupus nephritis via modulating the activation of NF-κB by targeting TNIP2.

Lupus nephritis (LN) is a kidney disorder resulting from systemic lupus erythematosus (SLE), an autoimmune inflammatory disease. MicroRNAs (miRNAs) have emerged as a new class of therapeutic targets in LN treatment, but how they specifically contribute to the disease development remains unknown. In this study, the expression of miR-663a/miR-423-5p and TNIP2 were compared between human renal biopsy tissues from LN patients and renal cell carcinoma patients. Additionally, the LN mouse model was used to measure the levels of miR-663a/miR-423-5p and TNIP2 in the control group and the experiment group. Dual luciferase reporter assay was used to validate TNIP2 as the target of miR-663a/miR-423-5p. MiR-663a/miR-423-5p were highly expressed in kidney tissues from LN patients as compared to kidney tissues from SLE patients and normal tissues. TNIP2 showed comparatively low expression in tissues from LN patients. In the LN mouse model, the levels of miR-663a/miR-423-5p were improved whereas TNIP2 was reduced in response to renal injury stimulated by pristine. MiR-663a/miR-423-5p mimics and inhibitors triggered decrease and increase of TNIP2 levels, respectively. Dual luciferase assay showed that TNIP2 was a direct target of miR-663a/miR-423-5p. In addition, detection of inflammatory factors confirmed that miR-663a/miR-423-5p and TNIP2 fundamentally contributed to LPS-induced NF-κB activation. Our findings suggested the involvement of miR-663a/miR-423-5p-TNIP2-NF-κB axis in the development of LN, thereby providing new therapeutic targets for LN treatment.

Emodin suppresses hyperglycemia-induced proliferation and fibronectin expression in mesangial cells via inhibiting cFLIP.

As one of the most serious microvascular complications of diabetes and a major cause of end stage renal disease, diabetic nephropathy (DN) is calling for effective treatment strategies. Here, we provide evidence that hyperglycemia can induce proliferation and decreasing apoptosis of mesangial cells (MCs) and subsequent renal dysfunction by up-regulating cellular FLICE-inhibitory protein (cFLIP). Treatment with emodin significantly turns down the accelerated cell cycle and proliferation of MCs cultured in high glucose (HG) via inhibiting cFLIP. In vitro, knockdown of cFLIP can arrest cell cycle and accelerate cell death by activating caspase-8, caspase-3 and caspase-9, and down-regulate proliferating cell nuclear antigen (PCNA). Our results also suggest that emodin regulates cFLIP expression in transcriptional level. Importantly, emodin lessens proteinuria and fibronectin expression in early-stage of streptozotocin (STZ)-induced diabetic rats. These findings demonstrate that emodin represent a promising strategy to prevent renal dysfunction in early-stage of diabetes mellitus.

Effect of spironolactone combined with angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers on chronic glomerular disease.

The aim of the present study was to observe the effects of spironolactone on urine protein level and kidney function in patients with chronic glomerular disease receiving angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor blockers (ARBs). A total of 221 patients with chronic glomerular disease were divided into spironolactone and control groups. The spironolactone group was treated with spironolactone at a dose of 20 mg/day, in addition to the original treatment regime and doses of ACEIs and/or ARBs. The control group continuously received the original doses of ACEIs and/or ARBs alone. Twenty-four-hour urine protein levels, serum creatinine and potassium, plasma aldosterone (ALD) and blood pressure were monitored at 0, 4, 8, 12 and 16 weeks. The estimated glomerular filtration rates (eGFRs) were calculated based on the obtained serum creatinine results. Following treatment, the urine protein level in the spironolactone group was notably decreased compared with that prior to the treatment, whereas the urine protein level in the control group did not show a significant difference. No significant differences were observed with regard to the renal function, eGFR, serum potassium, plasma ALD and blood pressure in either group prior to and following treatment. In conclusion, spironolactone administration, when co-administered with ACEIs and/or ARBs, markedly decreases the urine protein levels in patients with chronic glomerular disease. The protective effect of spironolactone on renal function remains to be demonstrated.

The linearity-improvement sigma-delta modulator for single-ended biomedical sensors.

A sigma-delta modulator which can improve the linearity of input original signal is proposed in this paper. The inverting and double sampling techniques are used in proposed modulator to convert the single-ended signal to fully differential signal. Therefore, the signal's linearity could be modified by the suppression of the even mode harmonic in fully differential circuit. With the proposed technique, the sensing biomedical signals could be more accurately acquired. The proposed modulator is designed in standard 0.18 microm 1P6M CMOS technology. The simulation results show that the linear errors of the CMOS thermal sensor and the PH electrochemical sensor are improved from 42.5% to 20.17%, 8.06% to 3.11%.

The power-efficient biomedical acquisition system by variable-resolution sigma-delta modulator.

A novel biomedical acquisition system which can adjust its resolution by the condition of signal is presented in this paper. The resolution of sigma-delta modulator in proposed system can be automatically varied by switching its architecture and sampling rate that can acquire accurate date without additional power consumption. The modulator in this system reaches specifications from 10-bit to 16-bit resolution and consumes power from 48microW to 360microW. In the electrocardiogram and electroculogram acquisition by proposed system, it can save more than 40% and 73% power consumption comparing with the conventional acquisition system.