Effect of Sijunzi Decoction on the Myonuclear Domain of Rat Soleus in Spleen Qi Deficiency

Objective: To study the mechanism of Sijunzi decoction treating limb weakness in spleen Qi deficiency (SQD) based on the myonuclear domain (MND) theory. Methods: 40 male Sprague-Dawley rats were randomly divided into the normal group, SQD model group (model group), SQD+ still water group (SW group) and SQD+ Sijunzi decoction group (CM group), 10 rats each group;Grip-Strength Meter was used to measure limb grip strength;transmission electron microscope was employed to observe the ultrastructural changes of the myofibers, Image Pro 6.0 was used to measure the myonuclear numbers, cross-section area (CSA) and then their ratios (the MND sizes) were calculated, immunofluorescence assay was chosen to test the expressions of paired box gene 7 (Pax7) and myogenic differentiation antigen (MyoD). Results: Compared with those in the normal group, limb grip strength was decreased, sarcomeres were abnormal, and all the myonuclear numbers, CSA and MND sizes were reduced, but the Pax7+ cell numbers were increased, significantly, in the model and SW groups;Compared with those in the model and SW groups, limb grip strength was increased, sarcomeres were basically normal, the myonuclear number and CSA were both greater, and the Pax7+ and MyoD+ cell numbers were both increased, significantly, in the CM group. Conclusion: Sijunzi decoction might increase the myonuclear number by activating the MSCs to treat limb weakness in SQD.

Fabrication and applications of van der Waals heterostructures

Van der Waals heterostructures(vdWHs) are showing considerable potential in both fundamental exploration and practical applications. Built upon the synthetic successes of(two-dimensional) 2D materials, several synthetic strategies of vdWHs have been developed,allowing the convenient fabrication of diverse vdWHs with decent controllability, quality, and scalability. This review first summarizes the current state of the art in synthetic strategies of vdWHs, including physical combination, deposition, solvothermal synthesis, and synchronous evolution. Then three major applications and their representative vdWH devices have been reviewed, including electronics(tunneling field effect transistors and 2D contact),optoelectronics(photodetector), and energy conversion(electrocatalysts and metal ion batteries), to unveil the potentials of vdWHs in practical applications and provide the general design principles of functional vdWHs for different applications. Besides, moiré superlattices based on vdWHs are discussed to showcase the importance of vdWHs as a platform for novel condensed matter physics. Finally, the crucial challenges towards ideal vdWHs with high performance are discussed, and the outlook for future development is presented. By the systematical integration of synthetic strategies and applications, we hope this review can further light up the rational designs of vdWHs for emerging applications.

Shape control on probability density function in stochastic systems

A novel strategy of probability density function(PDF) shape control is proposed in stochastic systems. The controller is designed whose parameters are optimally obtained through the improved particle swarm optimization algorithm. The parameters of the controller are viewed as the space position of a particle in particle swarm optimization algorithm and updated continually until the controller makes the PDF of the state variable as close as possible to the expected PDF. The proposed PDF shape control technique is compared with the equivalent linearization technique through simulation experiments. The results show the superiority and the effectiveness of the proposed method. The controller is excellent in making the state PDF follow the expected PDF and has the very small error between the state PDF and the expected PDF, solving the control problem of the PDF shape in stochastic systems effectively.

A Novel PDF Shape Control Approach for Nonlinear Stochastic Systems

In this work,a novel shape control approach of the probability density function(PDF)for nonlinear stochastic systems is presented.First,we provide the formula for the PDF shape controller without devising the control law of the controller.Then,based on the exact analytical solution of the Fokker-PlanckKolmogorov(FPK)equation,the product function of the polynomial and the exponential polynomial is regarded as the stationary PDF of the state response.To validate the performance of the proposed control approach,we compared it with the exponential polynomial method and the multi-Gaussian closure method by implementing comparative simulation experiments.The results show that the novel PDF shape control approach is effective and feasible.Using an equal number of parameters,our method can achieve a similar or better control effect as the exponential polynomial method.By comparison with the multiGaussian closure method,our method has clear advantages in PDF shape control performance.For all cases,the integral of squared error and the errors of first four moments of our proposed method were very small,indicating superior performance and promising good overall control effects of our method.The approach presented in this study provides an alternative for PDF shape control in nonlinear stochastic systems.

Anti-melanoma action of small molecular peptides derived from Brucea javanica(L.)Merr.globulin in vitro

Objective:The morbidity of malignant melanoma keeps increasing annually.It has high risks of metastasis,drug resistance,and poor prognosis in clinics.Moreover,the available medicines used commonly,such as dacarbazine,temozolomide,the v-Raf murine sarcoma viral oncogene homolog B1(BRAF)inhibitor vemurafenib,and the programmed cell death protein 1 inhibitor pembrolizumab,have some limitations at some extent.Therefore,a more effective therapeutic strategy is still urgently necessary.Methods:In this study,Brucea javanica(L.)Merr.globulins were hydrolyzed with pepsin,then ultra-filtrated to collect small molecular peptides(≤3 kDa).The peptides were then analyzed by antiproliferative assay,cell-cycle distribution,apoptosis assay,and in vitro wound-scratch assay.Finally,western blotting was conducted to elucidate the underlying anti-melanoma mechanism.Results:The small molecular peptide from B.javanica significantly inhibited malignant melanoma cell proliferation with the IC_(50) of 2.72 mg/mL for 72 h.Further analysis indicated that B.javanica peptides arrested cell cycle at the S and G2/M phases and induced apoptosis by upregulating p21,p53,Bax,caspase-3,and cleaved PARP while downregulating Bcl-2 expression.The inhibitory migration effects were also confirmed by wound-healing assay.Conclusion:The small molecular biopeptides from B.javanica may be a promising bioactive agent candidate for melanoma treatment.

Expression Imbalance of Cholinergic M₂and M₃Receptors Contributes to the Motility Reduction of the Small Intestine in Spleen Qi Deficiency

Objective: To study roles of cholinergic M2 and M3 receptors in the motility reduction of small intestine (SI) in spleen qi deficiency. Methods: 16 male SD rats were randomly divided in the control group and spleen qi deficiency group (model group)—8 rats each group;spleen qi deficiency model of the improper diet and overfatigue was established;the SI propelling rate (SIPR) was used to evaluate the SI motility;ELISA was used to measure concentrations of acetylcholine (ACh), cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the SI tissue;immohistochemistry was employed to detect expressions of cholinergic M2 and M3 receptors. Results: Compared with those in the control group, SIPR was reduced;expression of M2 receptors was increased;and expression of M3 receptors and concentrations of cAMP and PKA were decreased, significantly, in the model group. Conclusions: Expression imbalance of cholinergic M2 and M3 receptors might contribute to the motility reduction of the SI in spleen qi deficiency.

Average Life Prediction Based on Incomplete Data

The two-parameter exponential distribution can often be used to describe the lifetime of products for example, electronic components, engines and so on. This paper considers a prediction problem arising in the life test of key parts in high speed trains. Employing the Bayes method, a joint prior is used to describe the variability of the parameters but the form of the prior is not specified and only several moment conditions are assumed. Under the condition that the observed samples are randomly right censored, we define a statistic to predict a set of future samples which describes the average life of the second-round samples, firstly, under the condition that the censoring distribution is known and secondly, that it is unknown. For several different priors and life data sets, we demonstrate the coverage frequencies of the proposed prediction intervals as the sample size of the observed and the censoring proportion change. The numerical results show that the prediction intervals are efficient and applicable.

Mitophagy in the Skeletal Muscle Is Suppressed in Spleen Qi Deficiency

Objective: Mitochondrial impairment in the skeletal muscle contributes to useless of limbs in spleen qi deficiency;however the genesis of such impairment is not clear. Herein, PTEN-induced putative kinase 1 (PINK1)-Parkin pathway and mitophagy were studied to explore the machinery of mitochondrial impairment. Methods: 16 male SD rats were randomly divided in the control group and spleen qi deficiency group (model group);transmission electron microscope was used to observe mitochondrial morphology;mitochondrial oxidative phosphorylation was assessed by testing mitochondrial membrane potential (MMP) and levels of ATP and ROS;western blot was used to analyze expressions of PINK1, Parkin, microtubule-associated protein 1 light chain 3-II (LC3-II) and p62. Results: Compared with those in the control group, mitochondria became small, less and scattered, MMP and the ATP level were reduced, the ROS level was elevated, PINK1 expression was decreased, p62 expression was increased, but Parkin and LC3-II expressions were not altered, in the model group. Conclusions: Suppression of mitophagy might be related to the mitochondrial damage in the skeletal muscle when spleen qi deficiency develops.

The dusty and extremely red progenitor of the typeⅡsupernova 2023ixf in Messier 101

Stars with initial masses in the range of 8-25 solar masses are thought to end their lives as hydrogen-rich supernovae(SNeⅡ).Based on the pre-explosion images of Hubble space telescope(HST)and Spitzer space telescope,we place tight constraints on the progenitor candidate of type IIP SN 2023ixf in Messier 101.Fitting of the spectral energy distribution(SED)of its progenitor with dusty stellar spectral models results in an estimation of the effective temperature as 3091+422-258K.The luminosity is estimated as lg(L/L⊙)~4.83,consistent with a red supergiant(RSG)star with an initial mass of 12-1+2M⊙.The derived mass loss rate(6×10^(-6)-9×10^(-6)M⊙yr^(-1))is much lower than that inferred from the flash spectroscopy of the SN,suggesting that the progenitor experienced a sudden increase in mass loss when approaching the final explosion.In the infrared bands,significant deviation from the range of regular RSGs in the color-magnitude diagram and period-luminosity space of the progenitor star indicates enhanced mass loss and dust formation.Combined with new evidence of polarization at the early phases of SN 2023ixf,such a violent mass loss is likely a result of binary interaction.

On-tissue chemical derivatization enables spatiotemporal heterogeneity visualization of oxylipins in esophageal cancer xenograft via ambient mass spectrometry imaging

On-tissue chemical derivatization(OTCD)effectively enhances ionization efficiency of low abundant and poorly ionized functional molecules to improve detection sensitivity and coverage of mass spectrometry imaging(MSI).Combination OTCD and MSI provides a novel strategy for visualizing previously undisclosed metabolic heterogeneity in tumor.Herein,we present a method to visualize heterogeneous metabolism of oxylipins within tumor by coupling OTCD with airflow-assisted desorption electrospray ionization(AFADESI)-MSI.Taking Girard’s P as a derivatization reagent,easily ionized hydrazide and quaternary amine groups were introduced into the structure of carbonyl metabolites via condensation reaction.Oxylipins,including 127 fatty aldehydes(FALs)and 71 oxo fatty acids(FAs),were detected and imaged in esophageal cancer xenograft with AFADESI-MSI after OTCD.Then t-distributed stochastic neighbor embedding and random forest were exploited to precisely locate the distribution of oxylipins in heterogeneous tumor tissue.With this method,we surprisingly found almost all FALs and oxo FAs significantly accumulated in the core region of tumor,and exhibited a gradual increase trend in tumor over time.These results reveal spatiotemporal heterogeneity of oxylipins in tumor progression,highlighting the value of OTCD combined with MSI to gain deeper insights into understanding tumor metabolism.

Fluorinated inverse opal carbon nitride combined with vanadium pentoxide as a Z-scheme photocatalyst with enhanced photocatalytic activity

In this work,Z-scheme V_(2)O_(5) loaded fluorinated inverse opal carbon nitride(IO F-CN/V_(2)O_(5)) was synthesized as a product of ternary collaborative modification with heterostructure construction,element doping and inverse opal structure.The catalyst presented the highest photocatalytic activity and rate constant for degradation of typical organic pollutants Rhodamine B(RhB)and was also used for the efficient removal of antibiotics,represented by norfloxacin(NOR),sulfadiazine(SD)and levofloxacin(LVX).Characterizations confirmed its increased specific surface area,narrowed bandgap,and enhanced visible light utilization capacity.Further mechanism study including band structure study and electron paramagnetic resonance(EPR)proved the successful construction of Z-scheme heterojunction,which improved photogenerated charge carrier migration and provide sufficient free radicals for the degradation process.The combination of different modifications contributed to the synergetic improvement of removal efficiency towards different organic pollutants.

Pan-CDK inhibition augments cisplatin lethality in nasopharyngeal carcinoma cell lines and xenograft models

In addition to their canonical roles in regulating cell cycle transition and transcription,cyclin-dependent kinases(CDKs)have been shown to coordinate DNA damage response pathways,suggesting a rational pairing of CDK inhibitors with genotoxic chemotherapeutic agents in the treatment of human malignancies.Here,we report that roniciclib(BAY1000394),a potent pan-CDK inhibitor,displays promising anti-neoplastic activity as a single agent and potentiates cisplatin lethality in preclinical nasopharyngeal carcinoma(NPC)models.Proliferation of the NPC cell lines HONE-1,CNE-2,C666-1,and HK-1 was effectively curbed by roniciclib treatment,with IC_(50)values between 11 and 38 nmol/L.These anticancer effects were mediated by pleiotropic mechanisms consistent with successful blockade of cell cycle CDKs 1,2,3,and 4 and transcriptional CDKs 7 and 9,ultimately resulting in arrest at G1/S and G2/M,downregulation of the transcriptional apparatus,and repression of anti-apoptotic proteins.Considerably enhanced tumor cell apoptosis was achieved following combined treatment with 10 nmol/L roniciclib and 2.0μmol/L cisplatin;this combination therapy achieved a response over 250%greater than either drug alone.Although roniciclib chemosensitized NPC cells to cisplatin,it did not sensitize untransformed(NP69)cells.The administration of 0.5 mg/kg roniciclib to BALB/c xenograft mice was well tolerated and effectively restrained tumor growth comparable to treatment with 6 mg/kg cisplatin,whereas combining these two agents produced far greater tumor suppression than either of the monotherapies.In summary,these data demonstrate that roniciclib has strong anti-NPC activity and synergizes with cisplatin chemotherapy at clinically relevant doses,thus justifying further evaluation of this combinatorial approach in clinical settings.