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The etiology of Temporomandibular disorders (TMD) is still unclear, and its symptoms, signs, and progression are extremely complex. TMD requires early diagnosis and treatments, especially for combinations with other oral diseases. The research targets at developing an artificial neural network (ANN) model for predicting TMD based on clinical-collected data including clinical features, systematic medical condition, and psychosocial state. The popular data mining-based ANN was utilized to predict TMD with all 18 variables collected from patients as the input. The total dataset consists of 88 cases which were reviewed by Board-certificated orthodontists. 75% (66) cases are randomly selected as the training dataset, while the remaining 25% (22) cases are for test. Among the considered 88 cases, 58 (65.9%) were with TMD, while the left 30 (34.1%) without TMD. The numbers of male and female were 21 and 67, respectively, while the average age was 27.63 years. The calculated average sensitivity and specificity of ANN-based TMD risk predictions through 10-fold-cross-validation analysis were 92.31% (95% confidence interval (CI), 62.09%-99.60%) and 88.89% (95% CI, 50.67%-99.42%), respectively. Moreover, the accuracy rate of ANN was 90.91% (95% CI, 78.90%-100.00%). The results show the proposed ANN model could predict the TMD risks with a high accuracy rate, indicating the potential of machine learning in oral and maxillofacial diseases screening and diagnosis, which was further illustrated in a comparison with two doctors. This study can help dental care providers to find individuals’ risk of TMD by inputting patient’s psychological factors, oral examinations, and systemic medical conditions to the developed artificial intelligence (AI) model.

[INLINE:1] Administration of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) is believed to be an effective method for treating neurodevelopmental disorders. In this study, we investigated the possibility of hUC-MSCs treatment of neonatal hypoxic/ischemic brain injury associated with maternal immune activation and the underlying mechanism. We established neonatal rat models of hypoxic/ischemic brain injury by exposing pregnant rats to lipopolysaccharide on day 16 or 17 of pregnancy. Rat offspring were intranasally administered hUC-MSCs on postnatal day 14. We found that polypyrimidine tract-binding protein-1 (PTBP-1) participated in the regulation of lipopolysaccharide-induced maternal immune activation, which led to neonatal hypoxic/ischemic brain injury. Intranasal delivery of hUC-MSCs inhibited PTBP-1 expression, alleviated neonatal brain injury-related inflammation, and regulated the number and function of glial fibrillary acidic protein-positive astrocytes, thereby promoting plastic regeneration of neurons and improving brain function. These findings suggest that hUC-MSCs can effectively promote the repair of neonatal hypoxic/ischemic brain injury related to maternal immune activation through inhibition of PTBP-1 expression and astrocyte activation.

The alkylation of benzene with methanol can effectively generate high-value-added toluene and xylene out of surplus benzene, which is now achieved primarily using solid acids like H-ZSM-5 zeolites as catalysts. In this work, two H-ZSM-5 samples with distinct framework aluminum (AlF) distributions, but otherwise quite similar textural and acidic properties, have been prepared by employing tetrapropylammonium hydroxide (TPAOH) and n-butylamine (NBA) as organic structure-directing agents (OSDAs). Systematical investigations demonstrate that AlF is preferentially located at the intersections in MFI topology when TPAOH is adopted. In contrast, less AlF is positioned therein as NBA is utilized. Density functional theory (DFT) calculations reveal that the transition-state complexes cannot be formed in the straight and sinusoidal channels due to their much smaller sizes than the dynamic diameters of transition states, whereas there are adequate spaces for the formation of transition states at the intersections. Benefitting from abundant AlF at the intersections, which provides more acid sites therein, H-ZSM-5 synthesized from TPAOH is more active relative to the counterpart obtained from NBA. At a WHSV of 4 h−1 and 400 °C, the former catalyst gives a 52.8% conversion, while the latter one affords a 45.9% conversion. Both catalysts display close total selectivity towards toluene and xylene (ca. 84%). This study provides an efficient way to regulate the distribution of acid sites, thereby enhancing the catalytic performance of H-ZSM-5 zeolite in the titled reaction.

We used an in vitro model of the human brain immune microenvironment to simulate hypoxic-ischemic brain injury (HIBI) and treatment with human umbilical cord mesenchymal stem cells (hUMSCs) to address the transformation barriers of gene differences between animals and humans in preclinical research. A co-culture system, termed hNAME, consisted of human hippocampal neurons (N), astrocytes (A), microglia (M), and brain microvascular endothelial cells (E). Flow cytometry measured the apoptosis rates of neurons and endothelial cells. hNAME-neurons and endothelial cells experienced more severe damage than monolayer cells, particularly after 48 h and 24 h of reoxygenation (OGD48/R24). Western blotting identified neuroinflammatory response markers, including HIF-1α, C1q, C3, TNF-α, and iNOS. Inflammatory factors originated from the glial chamber rather than the neurons and vascular endothelial chambers. A gradual increase in the release of inflammatory factors was observed as the OGD and reoxygenation times increased, peaking at OGD48/R24. The hNAME value was confirmed in human umbilical cord mesenchymal stem cells (hUMSCs). Treatment with hUMSCs resulted in a notable decrease in the severity of neuronal and endothelial cell damage in hNAME. The hNAME is an ideal in vitro model for simulating the immune microenvironment of the human brain because of the interactions between neurons, vessels, astrocytes, and microglia.

Many non-traditional isotopes, such as chlorine, magnesium, calcium, etc., are widely used as groundwater tracers. A new sample processing protocol of purification and concentration for isotopic analysis is presented to overcome many of the major drawbacks of existing methods. Contemporary sample preparation often requires several laborious off-line procedures in a ultra clean laboratory prior to instrumental determination; additionally, interference ions in real samples are difficult to completely remove, especially when the concentration of those ions is equal to that of the target ions. The new protocol includes the following steps: (i) one-step purification using a newly developed isotopic preparative chromatograph (IPC) with a background suppressed mode to obtain extremely pure components that only have target ions and H2O; (ii) enrichment of the collected pure solution from the previous step using a newly developed ultra clean concentrator filled with high purity nitrogen; (iii) transforming the enriched target ion into suitable speciation inside the ultra clean concentrator; (iv) finally, sending the enriched solutions to a multi-collector inductively coupled-plasma mass-spectrometer (MC-ICP-MS) or thermal ionization mass spectrometer (TIMS). The present method was validated using certified reference materials and real samples for both chlorine and magnesium; the precision of chlorine ratio value was generally below 0.22‰ and that of Mg was below 0.12‰. This processing protocol provides a potential method for isotope sample preparation and analysis in a small number of geological samples with low concentrations of many other elements or compounds such as nitrate, sulfate, lithium, calcium, strontium, etc.

Intracerebral hemorrhage (ICH) is the most lethal type of stroke. Secondary injury from ICH determines the recovery, but there is still a lack of effective treatment. The identification of new therapeutic targets may address the current dilemma. The process of autophagy is mediated through the lysosomal pathway and is used to maintain cell homeostasis. Recent studies have advanced our knowledge of autophagy, and in particular its involvement in cell physiology and pathology. Autophagy involves multiple targets and signaling pathways and occurs in many brain cells. It also regulates oxidative stress and inflammation after ICH, both of which are important factors in secondary brain injury. An appropriate level of autophagy is protective in ICH, whereas excessive autophagy may be detrimental. In this review, we discuss the signaling pathways for autophagy in ICH and related factors that provide a theoretical basis for the discovery of new treatment targets.

Farmland transfer is a crucial aspect of modernizing China’s agriculture, which has a significant impact on farmers’ income distribution. With rapid urbanization, farmers’ livelihood has changed significantly, and the income effects of farmland transfer will differ among heterogeneous farmers. Based on the China Family Panel Studies (CFPS) data, this study examines the impact of farmland transfer on farmers’ income growth and income disparity, as well as the income differences in farmland transfer among farmers with different types of livelihood capital. An endogenous switching regression model and unconditional quantile treatment effects are used to correct the selection bias and farmer heterogeneity. The results show that (1) farmland transfer increases farmers’ income. Specifically, farmland transfer-in increases farmers’ income by 21.15%, while transfer-out increases it by 43.33%. (2) The impact of farmland transfer on farmers’ income has a “Matthew effect” and will widen the income gap between farmers. (3) Moreover, farmland transfer exhibits diverse income effects on heterogeneous farmers with livelihood capital. Capital-rich farmers experience the largest income-growth effect from farmland transfer-in, while capital-balanced farmers experience the largest income-growth effect from farmland transfer-out. The policy implications are to further improve the farmland transfer market and enable low-income farmers to participate by improving their qualifications and abilities.

A composite electrode of carbon nanotube CNT@Mn3O4 nanocable was successfully synthesized via direct electrophoretic deposition onto a copper foil, followed by calcination. By uniformly depositing Mn3O4 nanoparticles on CNTs, a nanocable structure of CNT@Mn3O4 can be formed, where the CNT acts as a “highway” for electrons and ions to facilitate fast transportation. Moreover, capacitive energy storage processes play a crucial role in lithium (Li) storage, especially during high scan rates. The significant contribution of capacitance is highly advantageous for the rapid transfer of Li+ ions, which ultimately results in an improved reversible capacity and prolonged cycle stability of the battery. A high specific capacity of 1367 mAh g−1 was maintained over 300 charge–discharge cycles at a current density of 1 A g−1, indicating excellent capacity retention and an extended cycle life. Furthermore, the synthesis process was facile and cost-effective, obviating the need for complex procedures such as mixing and pasting. Additionally, no binder was required, thereby enhancing battery quality efficiency.

Abstract Background A variety of hematopoietic abnormalities are commonly seen in human immunodeficiency virus-1 (HIV-1) infected individuals despite antiviral therapy, but the underlying mechanism remains elusive. Nef plays an important role in HIV-1 induced T cell loss and disease progression, but it is not known whether Nef participates in other hematopoietic abnormalities associated with infection. Results In the current study we investigated the influence of HIV-1LAI Nef (LAI Nef) on the development of hematopoietic stem/progenitor cells (HSPCs) into myeloid-erythroid lineage cells, and found that nef expression in HSPCs blocked their differentiation both in vitro and in humanized mice reconstituted with nef-expressing HSPCs. Conclusions Our novel findings demonstrate LAI Nef compromised the development of myeloid-erythroid lineage cells, and therapeutics targeting Nef would be promising in correcting HIV-1 associated hematopoietic abnormalities.

IntroductionRadiation-induced oxygen depletion in tissue is assumed as a contributor to the FLASH sparing effects. In this study, we simulated the heterogeneous oxygen depletion in the tissue surrounding the vessels and calculated the proton FLASH effective-dose-modifying factor (FEDMF), which could be used for biology-based treatment planning.MethodsThe dose and dose-weighted linear energy transfer (LET) of a small animal proton irradiator was simulated with Monte Carlo simulation. We deployed a parabolic partial differential equation to account for the generalized radiation oxygen depletion, tissue oxygen diffusion, and metabolic processes to investigate oxygen distribution in 1D, 2D, and 3D solution space. Dose and dose rates, particle LET, vasculature spacing, and blood oxygen supplies were considered. Using a similar framework for the hypoxic reduction factor (HRF) developed previously, the FEDMF was derived as the ratio of the cumulative normoxic-equivalent dose (CNED) between CONV and UHDR deliveries.ResultsDynamic equilibrium between oxygen diffusion and tissue metabolism can result in tissue hypoxia. The hypoxic region displayed enhanced radio-resistance and resulted in lower CNED under UHDR deliveries. In 1D solution, comparing 15 Gy proton dose delivered at CONV 0.5 and UHDR 125 Gy/s, 61.5% of the tissue exhibited ≥20% FEDMF at 175 μm vasculature spacing and 18.9 μM boundary condition. This percentage reduced to 34.5% and 0% for 8 and 2 Gy deliveries, respectively. Similar trends were observed in the 3D solution space. The FLASH versus CONV differential effect remained at larger vasculature spacings. A higher FLASH dose rate showed an increased region with ≥20% FEDMF. A higher LET near the proton Bragg peak region did not appear to alter the FLASH effect.ConclusionWe developed 1D, 2D, and 3D oxygen depletion simulation process to obtain the dynamic HRF and derive the proton FEDMF related to the dose delivery parameters and the local tissue vasculature information. The phenomenological model can be used to simulate or predict FLASH effects based on tissue vasculature and oxygen concentration data obtained from other experiments.

BackgroundAsthma is a major global health challenge. The global strategic management and prevention of asthma report has been published, but health system planning for asthma requires a careful assessment of asthma epidemiology. This study described the incidence and mortality of global asthma from 1990 to 2019.MethodsBased on data from the global burden of disease study (GBD) 2019, we present spatial and temporal trends in asthma incidence and mortality for the world and its 204 countries and territories from 1990 to 2019. Meanwhile, age-period-cohort analysis was used to explore factors influencing asthma incidence and mortality.ResultsFrom 1990 to 2019, the incidence of asthma decreased from 601.20 per 1,00,000 to 477.92 per 1,00,000, and the mortality of asthma decreased from 8.60 per 1,00,000 to 5.96 per 1,00,000. High sociodemographic index (SDI) areas have higher age-standardised asthma incidence and low sociodemographic index areas have higher age-standardised asthma mortality. The age-period-cohort analysis results showed that the relative risk (RR) of incidence was high in children and the RR of mortality was high in elderly individuals. The RR of both asthma incidence and mortality showed a decreasing trend over time. The RR of asthma incidence in the recent birth cohort was higher than that in the previous birth cohort. The RR of asthma mortality continued to decline with the change in the birth cohort.ConclusionsGlobal asthma incidence and mortality decreased from 1990 to 2019. The decline in asthma incidence was mainly attributed to age effects and period effects, and the decline in asthma mortality was mainly attributed to period effects and cohort effects. Focusing on the risk of incidence in children and the risk of mortality in the elderly, promoting healthy lifestyles and controlling environmental risk factors can help to better control asthma.

Abstract Background and aim The objective of this retrospective, observational, noninterventional cohort study was to investigate prognostic factors of overall survival (OS) in patients with advanced non‐small cell lung cancer (aNSCLC) and to develop a novel prognostic model. Methods A total of 4049 patients with aNSCLC diagnosed between January 2011 and February 2020 who received atezolizumab, nivolumab, or pembrolizumab as second‐line monotherapy were selected from a real‐world deidentified database to build the cohort. Patients could not have received first‐line treatment with clinical study drug(s) nor immune checkpoint inhibitors including anti‐programmed cell death 1 (PD‐1)/programmed death‐ligand 1 (PD‐L1), and anti‐cytotoxic T‐lymphocyte‐associated protein 4 therapies. Results Patients had a median age of 69 years; 45% were female, 75% White, 70% had stage IV at initial diagnosis, and 70% had nonsquamous histology. A Cox proportional hazards model with lasso regularization was used to build a prognostic model for OS using 18 baseline demographic and clinical factors based on the real‐world data cohort. The risk‐increasing prognostic factors were abnormally low albumin and chloride levels, Eastern Cooperative Oncology Group performance status score ≥ 2, and abnormally high levels of alkaline phosphatase and white blood cells. The risk‐decreasing prognostic factors were PD‐L1 positivity, longer time from advanced diagnosis to start of first‐line therapy, and higher systolic blood pressure. The performance of the model was validated using data from the OAK trial, and the c‐index for the OAK trial validation cohort was 0.65 and 0.67 for the real‐world data cohort. Conclusions Based on baseline demographic and clinical factors from a real‐world setting, this prognostic model was developed to discriminate the risk of death in patients with aNSCLC treated with checkpoint inhibitors as second‐line monotherapy, and it performed well in the real‐world data and clinical trial cohorts.

Variable application by wind is an efficient application technology recommended by the Food and Agriculture Organization (FAO) of the United Nations that can effectively improve the deposition effect of liquid medicine in a canopy and reduce droplet drift. In view of the difficulty of modelling wind forces in orchard tree canopies and the lack of a wind control model, the wind loss model for a canopy was studied. First, a three-dimensional wind measurement test platform was built for an orchard tree canopy. The orchard tree was located in three-dimensional space, and the inner leaf areas of the orchard tree canopy and the wind force in different areas were measured. Second, light detection and ranging (LiDAR) point cloud data of the orchard tree canopy were obtained by LiDAR scanning. Finally, classic regression, partial least squares regression (PLSR), and back propagation (BP) neural network algorithms were used to build wind loss models in the canopy. The research showed that the BP neural network algorithm can significantly improve the fitting accuracy of the model. Under different fan speeds of 1,381 r/min, 1,502 r/min, and 1,676 r/min, the coefficient of determination (R2) of the model were 81.78, 72.85, and 69.20%, respectively, which were 19.38, 7.55, and 12.3% higher than those of the PLSR algorithm and 21.48, 22.25, and 24.3% higher than those of multiple regression analysis. The comparison showed that the BP neural network algorithm obtains the highest model accuracy, but because the model is not intuitive, PLSR has the advantages of intuitive and simple models in the three algorithms. In practical applications, the wind loss model based on a BP neural network or PLSR can be selected according to the operational requirements and software and hardware conditions. This study can provide a basis for wind control in precise variable spraying and promote the development of wind control technologies.

Cortical actin, a thin layer of actin network underneath the plasma membranes, plays critical roles in numerous processes, such as cell morphogenesis and migration. Neurons often grow highly branched dendrite morphologies, which is crucial for neural circuit assembly. It is still poorly understood how cortical actin assembly is controlled in dendrites and whether it is critical for dendrite development, maintenance and function. In the present study, we find that knock-out of C. elegans chdp-1, which encodes a cell cortex-localized protein, causes dendrite formation defects in the larval stages and spontaneous dendrite degeneration in adults. Actin assembly in the dendritic growth cones is significantly reduced in the chdp-1 mutants. PVD neurons sense muscle contraction and act as proprioceptors. Loss of chdp-1 abolishes proprioception, which can be rescued by expressing CHDP-1 in the PVD neurons. In the high-ordered branches, loss of chdp-1 also severely affects the microtubule cytoskeleton assembly, intracellular organelle transport and neuropeptide secretion. Interestingly, knock-out of sax-1, which encodes an evolutionary conserved serine/threonine protein kinase, suppresses the defects mentioned above in chdp-1 mutants. Thus, our findings suggest that CHDP-1 and SAX-1 function in an opposing manner in the multi-dendritic neurons to modulate cortical actin assembly, which is critical for dendrite development, maintenance and function.

Vaccines play an important role in maintaining human and animal health worldwide. There is continued demand for effective and safe adjuvants capable of enhancing antigen-specific responses to a target pathogen. Rabbit hemorrhagic disease virus (RHDV) is a highly contagious calicivirus that often induces high mortality rates in rabbits. Herein, we evaluated the activity of an experimental sulfated lactosyl archaeol (SLA) archaeosome adjuvant when incorporated in subunit vaccine formulations targeting RHDV. The subunit antigens consisted of RHDV–CRM197 peptide conjugates or recombinant RHDV2 VP60. SLA was able to enhance antigen-specific antibody titers and cellular responses in mice and rabbits. Three weeks following immunization, antigen-specific antibody levels in rabbits vaccinated with RHDV2 VP60 + SLA were significantly higher than those immunized with antigen alone, with geomean titers of 7393 vs. 117. In addition, the SLA-adjuvanted VP60-based formulations were highly efficacious in a rabbit RHDV2 challenge model with up to 87.5% animals surviving the viral challenge. These findings demonstrate the potential utility of SLA adjuvants in veterinary applications and highlight its activity in different types of mammalian species.

To improve the fresh-keeping of highly perishable fruits with high commercial value, a novel starch-based foam packaging material was developed in this study. The foam incorporated the antiseptic ingredient Na2S2O5, which chemically interacted with environmental moisture to release SO2 as an antifungal agent. Scanning electron microscopy (SEM), moisture absorption and mechanical measurements were used to characterize the unique sandwich-like inner structure of the foam which allowed for the modulable release of SO2. The starch-based foam exhibited sufficient resilience (~100%) to provide ideal cushioning to prevent physical damage to fresh fruits during transportation. When 25 g/m2 of Na2S2O5 was applied, the foam stably released over 100 ppm SO2 and demonstrated satisfactory antifungal performance (inhibition over 60%) in terms of maintaining the appearance and nutritional values (such as soluble solids 14 vs. 11%, total acidity 0.45 vs. 0.30%, and Vitamin C 3.4 vs. 2.5 mg/100 g) of fresh grapes during a 21 day storage period. Additionally, the residual SO2 (14 mg/kg) also meets the safety limits (

Pit mud (PM) is the main component of Baijiu (traditional Chinese liquor), and its microorganisms are the primary sources of the aroma of Chinese strong-flavor Baijiu (SFB). Enrichment plays an important role in the selection of functional microorganisms in PM. Herein, the PM of SFB was submitted to six rounds of enrichment using clostridial growth medium (CGM), and changes in the metabolite accumulation and microbiota composition were evaluated. Based on the metabolite production and microbiota composition, the enrichment rounds were classified as the acclimation stage (round 2), main fermentation stage (rounds 3 and 4), and late fermentation stage (rounds 5 and 6). Species within the genus Clostridium dominated in the acclimation stage (65.84–74.51%). In the main fermentation stage, the dominant microbial groups were producers of butyric acid, acetic acid, and caproic acid, which included Clostridium (45.99–74.80%), Caproicibacter (1.45–17.02%), and potential new species within the order of Oscillataceae (14.26–29.10%). In the late stage of enrichment, Pediococcus dominated (45.96–79.44%). Thus, the main fermentation stage can be considered optimal for the isolation of acid-producing bacteria from PM. The findings discussed herein support the development and application of functional bacteria by bioaugmentation, and contribute to improving the quality of PM and SFB production.

As a difficult-to-machine material widely used in the aerospace industry, the high-quality and efficient cutting of titanium alloys has been a hot issue in the field of machining. This work performed electric-pulse-assisted turning (EPT) and conventional turning (CT) for Ti5Al4Mo6V2Nb1Fe (TC27) alloy with two kinds of cutters. The results showed that electric pulses significantly improved the machining performance and surface finish quality. With the help of the electric pulse, the cutting force of TiAlN-coated cemented carbide insert (CCI) and uncoated carbide insert (UCI) tools during turning was reduced by more than 20%, and the surface roughness decreased by about 30% with a root mean square of the current density of 0.9 A/mm2, because the larger current led to a more obvious electro-plasticity effect. Compared with CT, the surface microhardness of the EPT samples processed with different current densities decreased; this is because the hardened surface was softened by both thermal and athermal effects under the continuous pulse current. However, the microhardness of the EPT samples was still higher than the matrix. At the same time, EPT reduces the wear of the cutting tool, thus helping to extend the tool’s service life. Finally, the electric pulse parameters recommended to assist turning are as follows: an electro-pulsing frequency of 600 Hz, a root mean square of the current density in the cross-section of 0.57 A/mm2, and a lasting time of the current per circle of 100 μs.

A novel fluorine-containing water-repellent agent (OFAE-SA-BA) was designed and synthesized by emulsion copolymerization, which was used to replace the commercial long fluorocarbon chain water-repellent agent. To improve water repellency, the intermediate and monomer containing two short fluoroalkyl chains were successfully synthesized and characterized by 1H NMR, 13C NMR and FT-IR, respectively. After being treated by the water-repellent agent, the surface chemical composition, molecular weight, thermal stability, surface morphology, wetting behavior, and durability of the modified cotton fabrics were characterized using X-ray photoelectron spectrophotometry (XPS), gel permeation chromatography (GPC), thermal degradation (TG), scanning electron microscopy (SEM), and video-based contact angle goniometry, respectively. The cotton fabric demonstrated water contact angle of 154.1°, both the water and oil repellency rating were grade 4. The durability of water repellency of the treated fabrics only decreased slightly after 30 times, which represented very good washing durability. The finishing agent did not affect the whiteness of the fabric.

Purpose: To describe an implementation of dual-energy computed tomography (DECT) for calculation of proton stopping-power ratios (SPRs) in a commercial treatment-planning system. The process for validation and the workflow for safe deployment of DECT is described, using single-energy computed tomography (SECT) as a safety check for DECT dose calculation. Materials and Methods: The DECT images were acquired at 80 kVp and 140 kVp and were processed with computed tomography scanner software to derive the electron density and effective atomic number images. Reference SPRs of tissue-equivalent plugs from Gammex (Middleton, Wisconsin) and CIRS (Computerized Imaging Reference Systems, Norfolk, Virginia) electron density phantoms were used for validation and comparison of SECT versus DECT calculated through the Eclipse treatment planning system (Varian Medical Systems, Palo Alto, California) application programming interface scripting tool. An in-house software was also used to create DECT SPR computed tomography images for comparison with the script output. In the workflow, using the Eclipse system application programming interface script, clinical plans were optimized with the SECT image set and then forward-calculated with the DECT SPR for the final dose distribution. In a second workflow, the plans were optimized using DECT SPR with reduced range-uncertainty margins. Results: For the Gammex phantom, the root mean square error in SPR was 1.08% for DECT versus 2.29% for SECT for 10 tissue-surrogates, excluding the lung. For the CIRS Phantom, the corresponding results were 0.74% and 2.27%. When evaluating the head and neck plan, DECT optimization with 2% range-uncertainty margins achieved a small reduction in organ-at-risk doses compared with that of SECT plans with 3.5% range-uncertainty margins. For the liver case, DECT was used to identify and correct the lipiodol SPR in the SECT plan. Conclusion: It is feasible to use DECT for proton-dose calculation in a commercial treatment planning system in a safe manner. The range margins can be reduced to 2% in some sites, including the head and neck.

Glioblastomas are generally resistant to treatment with immune checkpoint inhibitors. Here the authors show that IL6 blockade, in combination with a CD40 agonist, overcomes macrophage-mediated immunosuppression and sensitizes glioblastoma to immune checkpoint blockade in preclinical models.

BackgroundChest radiation therapy (RT) is known to be associated with cardiotoxicity. However, the changes in myocardial tissue characterization with radiation-induced cardiotoxicity are not well-understood.ObjectivesThis study sought to assess the changes in left ventricular function and tissue characterization using cardiovascular magnetic resonance (CMR) in patients receiving RT.Materials and MethodsBetween June 2015 and July 2018, we enrolled patients with breast, lung cancer, or lymphoma with plan to receive chest radiation after chemotherapy. CMR was performed using a 1.5T scanner at baseline and 6 months after RT. Myocardial volume, function, strain analysis using feature tracking, and tissue characterization including late gadolinium enhancement (LGE), T1, T2, T1ρ (rho), and extracellular volume fraction (ECV) were measured and compared using non-parametric methods.ResultsThe final cohort consisted of 16 patients, 11 of whom completed both baseline and follow-up CMRs. Patients were matched to 10 healthy controls. At baseline prior to RT, compared to controls, patients had lower global circumferential strain (GCS) (15.3 ± 2.2% vs.18.4 ± 2.1%, p = 0.004), and elevated T2 (47.9 ± 4.8 ms vs. 45.0 ± 1.5 ms, p = 0.04) and T1ρ values (78.4 ± 5.9 vs. 66.9 ± 4.6 ms, p < 0.001). Two patients had LGE. There was no significant difference in the average T1 values or ECV. There was a trend toward lower LV ejection fraction and global longitudinal strain (GLS). At 6-month follow-up after RT, there were no significant changes in all the CMR parameters.ConclusionAt 6-month following chest radiation therapy, there was no change in LV and RV EF, LV and RV GLS, LV GCS, and myocardial tissue characterization using LGE, T1, ECV, T2, and T1ρ in a small cohort of patients. However, the baseline T2 and T1ρ were elevated and LV GCS was reduced compared to controls indicating ongoing myocardial edema and subclinical dysfunction post-chemotherapy.

ABSTRACT Both LRF (Zbtb7a) and ThPOK (Zbtb7b) belong to the POK (BTB/POZ and Kruppel) family of transcription repressors that participate in development, differentiation, and oncogenesis. Although LRF mediates osteoclast differentiation by regulating NFATc1 expression, the principal established function of ThPOK is transcriptional control of T‐cell lineage commitment. Whether ThPOK affects osteoclast formation or function is not known. We find that marrow macrophage ThPOK expression diminishes with exposure to receptor activator of NF‐kB ligand (RANKL), but ThPOK deficiency does not affect osteoclast differentiation. On the other hand, enhanced ThPOK, in macrophages, substantially impairs osteoclastogenesis. Excess ThPOK binds the NFATc1 promoter and suppresses its transcription, suggesting a mechanism for its osteoclast inhibitory effect. Despite suppression of osteoclastogenesis by excess ThPOK being associated with diminished NFATc1, osteoclast formation is not rescued by NFATc1 overexpression. Thus, ThPOK appears to inhibit NFATc1 transcription and its osteoclastogenic capacity, while its depletion has no effect on the bone‐resorptive cell. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Polyomaviruses (PyV) are ubiquitous pathogens that can cause devastating human diseases. Due to the small size of their genomes, PyV utilize complex patterns of RNA splicing to maximize their coding capacity. Despite the importance of PyV to human disease, their transcriptome architecture is poorly characterized. Here, we compare short- and long-read RNA sequencing data from eight human and non-human PyV. We provide a detailed transcriptome atlas for BK polyomavirus (BKPyV), an important human pathogen, and the prototype PyV, simian virus 40 (SV40). We identify pervasive wraparound transcription in PyV, wherein transcription runs through the polyA site and circles the genome multiple times. Comparative analyses identify novel, conserved transcripts that increase PyV coding capacity. One of these conserved transcripts encodes superT, a T antigen containing two RB-binding LxCxE motifs. We find that superT-encoding transcripts are abundant in PyV-associated human cancers. Together, we show that comparative transcriptomic approaches can greatly expand known transcript and coding capacity in one of the simplest and most well-studied viral families.

Stroke’s secondary damage, such as inflammation, oxidative stress, and mitochondrial dysfunction, are thought to be crucial factors in the disease’s progression. Despite the fact that there are numerous treatments for secondary damage following stroke, such as antiplatelet therapy, anticoagulant therapy, surgery, and so on, the results are disappointing and the side effects are numerous. It is critical to develop novel and effective strategies for improving patient prognosis. The ubiquitin proteasome system (UPS) is the hub for the processing and metabolism of a wide range of functional regulatory proteins in cells. It is critical for the maintenance of cell homeostasis. With the advancement of UPS research in recent years, it has been discovered that UPS is engaged in a variety of physiological and pathological processes in the human body. UPS is expected to play a role in the onset and progression of stroke via multiple targets and pathways. This paper explores the method by which UPS participates in the linked pathogenic process following stroke, in order to give a theoretical foundation for further research into UPS and stroke treatment.

Ling Cai et al. used transcriptomic profiling data of healthy lung, patient-derived small cell lung cancer cell lines, xenografts, and primary tumors to examine a link between neuroendocrine (NE) signatures and immune gene expression. Their findings suggest that cell-autonomous immune gene repression is a shared feature between healthy and tumor cells of NE lineage and may influence tumor-immune cell interaction and response to immunotherapy.

Introduction: The intracranial skull-base meningioma is in proximity to multiple critical organs and heterogeneous tissues. Steep dose gradients often result from avoiding critical organs in proton treatment plans. Dose uncertainties arising from setup errors under image-guided radiation therapy are worthy of evaluation. Patients and Methods: Fourteen patients with skull-base meningioma were retrospectively identified and planned with proton pencil beam scanning (PBS) single-field uniform dose (SFUD) and multifield optimization (MFO) techniques. The setup uncertainties were assigned a probability model on the basis of prior published data. The impact on the dose distribution from nominal 1-mm and large, less probable setup errors, as well as the cumulative effect, was analyzed. The robustness of SFUD and MFO planning techniques in these scenarios was discussed. Results: The target coverage was reduced and the plan dose hot spot increased by all setup uncertainty scenarios regardless of the planning techniques. For 1 mm nominal shifts, the deviations in clinical target volume (CTV) coverage D99% was − 11 ± 52 cGy and − 45 ± 147 cGy for SFUD and MFO plans. The setup uncertainties affected the organ at risk (OAR) dose both positively and negatively. The statistical average of the setup uncertainties had

Bromodomain-containing protein 4 (BRD4) binds acetylated lysine residues on the N-terminal tails of histones through two bromodomains (BD1 and BD2) to regulate gene transcription. Inhibiting one or both of bromodomains resulted in different phenotypes, suggesting BD1 and BD2 may have different functions. Here we report the characterisation of a natural product 3',4',7,8-tetrahydroxyflavone as a novel and potent selective BRD4 inhibitor. The compound is 100-fold more selective for BRD4-BD2 (IC50 = 204 nM) than BRD4-BD1 (IC50=17.9 µM). Co-crystal structures show 3',4',7,8-tetrahydroxyflavone binds to the acetylated lysine binding pocket of BRD4-BD1 or BRD4-BD2, but establishes more interactions with BRD4-BD2 than BRD4-BD1. Our data suggest 3',4',7,8-tetrahydroxyflavone as a potent selective inhibitor of BRD4-BD2 with a novel chemical scaffold. Given its distinct chemical structure from current BRD4 inhibitors, this compound may open the door for a novel class of anti-BRD4 inhibitors by serving as a lead compound.

In this study, we explored the role and mechanism of repulsive guidance molecule B (RGMb, also known as Dragon) in the protective effects of curcumin against renal fibrosis and verified Dragon’s effect on renal tubular epithelial cell apoptosis and cell programmability. Unilateral ureteral obstruction (UUO) was surgically induced in rats to establish a model of renal interstitial fibrosis (RIF). The rats were then treated with curcumin. Curcumin prominently decreased the serum creatinine (SCr) and blood urea nitrogen (BUN) levels, and also improved the tubular injury in the UUO-induced rats. Curcumin significantly downregulated the TGF-β1, P-Smad2/3, cleaved caspase-3, cleaved caspase-8 and Dragon levels. Dragon knockdown also markedly reduced the TGF-β1, P-Smad2/3, Smad2/3, cleaved caspase-3, cleaved caspase-8, fibronectin, collagen I, collagen IV, vimentin, and α-SMA expression levels. Conversely, Dragon overexpression caused higher expression levels of these proteins, and curcumin reversed this effect. Furthermore, Dragon knockdown increased the E-cadherin levels, whereas Dragon overexpression decreased these levels. Overexpressing Dragon significantly decreased the cell viability, and curcumin reversed this effect. In conclusion, curcumin acted on Dragon and attenuated RIF in UUO rat models. Curcumin downregulated the TGF-β1/Smad signaling pathway and inhibited Dragon and fibrogenic molecules in both rats and HK-2 cells.

Previous studies have shown that caveolin-1 is involved in regulating the differentiation of mesenchymal stem cells. However, its role in the differentiation of human adipose mesenchymal stem cells into dopaminergic neurons remains unclear. The aim of this study was to investigate whether caveolin-1 regulates the differentiation of human adipose mesenchymal stem cells into dopaminergic-like neurons. We also examined whether the expression of caveolin-1 could be modulated by RNA interference technology to promote the differentiation of human adipose mesenchymal stem cells into dopaminergic-like neurons. The differentiation of human adipose mesenchymal stem cells into dopaminergic neurons was evaluated morphologically and by examining expression of the markers tyrosine hydroxylase, Lmx1a and Nurr1. The analyses revealed that during the differentiation of human adipose mesenchymal stem cells into dopaminergic neurons, the expression of caveolin-1 is decreased. Notably, the downregulation of caveolin-1 promoted the differentiation of human adipose mesenchymal stem cells into dopaminergic-like neurons, and it increased the expression of tyrosine hydroxylase, Lmx1a and Nurr1. Together, our findings suggest that caveolin-1 plays a negative regulatory role in the differentiation of dopaminergic-like neurons from stem cells, and it may therefore be a potential molecular target for strategies for regulating the differentiation of these cells. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Dalian Medical University of China (approval No. PJ-KS-KY-2020-54) on March 7, 2017.

Poverty is a critical issue in sustainable development, and the study of poverty has gradually shifted from absolute to relative poverty. This paper measures three types of relative poverty—strongly relative poverty (50% of median income), strongly relative poverty (50% of mean income), and weakly relative poverty. Then this paper decomposes the change of relative poverty into the growth component, redistribution component, and poverty line change component. Further, the intra- and inter-group decompositions of relative poverty change are carried out by considering the urban and rural population mobility components. We apply the China Health and Nutrition Survey (CHNS) data from 1989 to 2015 for an empirical study. The results show that: (1) In recent years, the change in relative poverty in China has shown a trend of low fluctuation (1989–1997), rising fluctuation (1997–2006), and high fluctuation (2006–2015). (2) In the decomposition of relative poverty change, the growth component has the most excellent effect on alleviating relative poverty, the redistribution component exacerbates the occurrence of relative poverty in most years and reduces it in a few years, and the poverty line change component offsets the poverty reduction effect of the growth component. (3) The change in relative poverty is decomposed by urban and rural sub-groups, and it is found that the population mobility from rural to urban can reduce the national relative poverty.

China has eliminated absolute poverty and begun to tackle relative poverty, yet the change in relative poverty in China has been less studied. In this paper, we develop a three-component decomposition of the change in relative poverty and apply it to analyze the relative poverty in China. The change in relative poverty is decomposed into identification, growth, and redistribution components. We compare the three-component decomposition with other decomposition methods in the existing literature and show the advantages of the former. Our study, using the China Family Panel Studies (CFPS) 2010–2018 data, shows that relative poverty is rising. Examining the periods of 2012–2014, 2014–2016, and 2016–2018, we show that the three components differ in their contribution to relative poverty. The identification component rises with income growth and increases relative poverty by 8.42%, 12.19%, and 12.55%, respectively. The growth component reduces the incidence of relative poverty by 8.34%, 11.24%, and 12.18%, respectively. In comparison, the redistribution component increases the incidence of relative poverty by 2.88%, 1.12%, and 6.60%, respectively.

In vitro digestion methods that can accurately predict the estimated GI (eGI) values of complex carbohydrate foods, including biscuits, are worth exploring. In the current study, standard commercial biscuits with varied clinical GI values between 9~30 were digested using both the INFOGEST and single-enzyme digestion protocols. The digestion kinetic parameters were acquired through mathematical fitting by mathematical kinetics models. The results showed that compared with the INFOGEST protocol, the AUR180 deduced from digesting using either porcine pancreatin or α-amylase showed the best potential in predicting the eGI values. Accordingly, mathematical equations were established based on the relations between the AUR180 and the GI values. When digesting using porcine pancreatin, GI= 1.834 + 0.009 ×AUCR180 (R2= 0.952), and when digesting using only α-amylase, GI= 6.101 + 0.009 ×AUCR180 (R2=0.902). The AUR180 represents the area under the curve of the reducing-sugar content normalized to the total carbohydrates versus the digestion time in 180 min. The in vitro method presented enabled the rapid and accurate prediction of the eGI values of biscuits, and the validity of the formula was verified by another batch of biscuits with a known GI, and the error rate of most samples was less than 30%.

Background: Few studies have explored the correlation between asthma medication and features on HRCT images. We aim to analyse the differences and temporal changes of lung function and airway resistance in asthma with diverse HRCT phenotypes in a short period after inhalation of budesonide/formoterol. Method: This observational study recruited 55 adult patients with varying severities of asthma. We performed detailed airway metrics measurements of chest CT scans, such as airway wall thickness (WT), wall area percentage (WA%), wall thickness percentage (T/OR), and airways with an inner perimeter of 10 mm (Pi10). The effect of lung structural features on asthma medication response was explored according to the WA% and T/OR twelve hours post-drug administration. Using multivariable regression models, we then assessed the influence of WA% on lung function. Results: WA% (p < 0.001) and T/OR (p < 0.001) significantly increased in asthma than in healthy control subjects. Compared to mild asthma, airway walls were further thickened (WA%, p = 0.023; T/OR: p = 0.029) and associated with lumen narrowing (Pi10, p = 0.055) in moderate to severe asthma. WA% and T/OR correlated well with lung function (FEV1, FVC, MMEF, and PEF) and airway resistance (R5, R20, Rp, and Fres). Regression analysis showed that MEF25 decreased with increasing age and WA% (R2 = 0.58, p < 0.001). Patients with thickened airway walls experienced a maximal increase in FVC, FEV1, and PEF at 2 h (p < 0.001) and a maximal decrease of R5, Z5, and Rp at 2 h (p < 0.001) in those with a thickened airway pattern. Conclusions: Asthma patients with different bronchial wall thicknesses exhibited variable lung function changes. Specifically, patients with thick airway wall patterns were more sensitive to inhaled budesonide in the short term.

Abstract Background This study investigates daily breast geometry and delivered dose to prone-positioned patients undergoing tangential whole breast radiation therapy (WBRT) on an O-ring linear accelerator with 6X flattening filter free mode (6X-FFF), planned with electronic compensation (ECOMP) method. Most practices rely on skin marks or daily planar image matching for prone breast WBRT. This system provides low dose daily CBCT, which was used to study daily robustness of delivered dose parameters for prone-positioned WBRT. Methods Eight patients treated with 16-fraction prone-breast WBRT were retrospectively studied. Planning CTs were deformed to daily CBCT to generate daily synthetic CTs, on which delivered dose distributions were calculated. A total of 8 × 16 = 128 synthetic CTs were generated. Consensus ASTRO definition was used to contour Breast PTV Eval for each daily deformed CT. Breast PTV Eval coverage (V90%) and hotspot (V105% and Dmax) were monitored daily to compare prescription dose with daily delivered dose. Various predictors including patient weight, breast width diameter (BWD), and Dice similarity coefficient (DSC) were fit into an analysis of covariance model predicting V90% and V105% deviation from prescribed (ΔV90%, ΔV105%). Statistical significance is indicated with asterisks (* for p

The major aim of radiation therapy is to provide curative or palliative treatment to cancerous malignancies while minimizing damage to healthy tissues. Charged particle radiotherapy utilizing carbon ions or protons is uniquely suited for this task due to its ability to achieve highly conformal dose distributions around the tumor volume. For these treatment modalities, uncertainties in the localization of patient anatomy due to inter- and intra-fractional motion present a heightened risk of undesired dose delivery. A diverse range of mitigation strategies have been developed and clinically implemented in various disease sites to monitor and correct for patient motion, but much work remains. This review provides an overview of current clinical practices for inter and intra-fractional motion management in charged particle therapy, including motion control, current imaging and motion tracking modalities, as well as treatment planning and delivery techniques. We also cover progress to date on emerging technologies including particle-based radiography imaging, novel treatment delivery methods such as tumor tracking and FLASH, and artificial intelligence and discuss their potential impact towards improving or increasing the challenge of motion mitigation in charged particle therapy.

Constructing a three-dimensional (3D) multifunctional hosting architecture and subsequent thermal infusion of molten Li to produce advanced Li composite is an effective strategy for stable Li metal anode. However, the pure liquid Li is difficult to spread across the surface of various substrates due to its large surface tension and poor wettability, hindering the production and application of Li composite anode. Herein, heteroatomic Ca is doped into molten Li to generate Li-Ca alloy, which greatly regulates the surface tension of the molten alloy and improves the wettability against carbon cloth (CC). Moreover, a secondary network composed of CaLi2 intermetallic compound with interconnected ant-nest-like lithiophilic channels is in situ formed and across the primary scaffold of CC matrix by infiltrating molten Li-Ca alloy into CC and then cooling treatment (LCAC), which has a larger and lithiophilic surface to enable uniform Li deposition into interior space of the hybrid scaffold without Li dendrites. Therefore, LCAC exhibits a long-term lifespan for 1100 h under a current density of 5 mA cm-2 with fixed areal capacity of 5 mAh cm-2. Remarkably, full cells paired with practical-level LiFePO4 cathode of 2.45 mAh cm-2 deliver superior performance.

The safety of microplastics (MPs) and associated health effects has been one of the major concerns worldwide. However, the role of photoaging toward the risk of MPs in water ecosystems remains inconclusive yet. In this study, the size of polyamide (PA, ∼32.50 μm) MPs was obviously decreased after photoaging in water containing fulvic acid (FA) and humic acid (HA) (∼19.75 and ∼24.30 μm, respectively). Nanoplastics were formed (4.65% and 2.03%, respectively) and hydrophilia and colloidal stability was improved due to the formation of oxygen-containing functional groups. FA-aged PA exhibited higher inhibition on body length and weight of developing zebrafish than HA-aged and pristine PA. Photoaged MPs in intestine were more difficult to be depurated by zebrafish, leading to the disappearance of intestinal folding, shedding of more enterocytes, and emaciation of intestinal microvilli. Dietary lipid digestion in larvae was inhibited by aged PA due to oxidative stress-triggered lipid peroxidation and inhibition of lipase activities and bile acids secretion. Exposure of photoaged MPs down-regulated genes (cd36, dgat1a, dgat2, mttp, etc.) associated with triglyceride resynthesis and transportation, resulting in lipid maladsorption and growth inhibition. Our findings highlight the potential negative effects of environmentally aged MPs on diet digestion and nutrient assimilation in fish.

Purpose: The dosimetric parameters used clinically to reduce the likelihood of radiation pneumonitis (RP) for lung cancer radiation therapy have traditionally been V20Gy ≤ 30% to 35% and mean lung dose ≤ 20 to 23 Gy; however, these parameters are derived based on studies from photon therapy. The purpose of this study is to evaluate whether such dosimetric predictors for RP are applicable for locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with proton therapy. Methods and Materials: In the study, 160 (78 photon, 82 proton) patients with LA-NSCLC treated with chemoradiotherapy between 2011 and 2016 were retrospectively identified. Forty (20 photon, 20 proton) patients exhibited grade ≥2 RP after therapy. Dose volume histograms for the uninvolved lung were extracted for each patient. The percent lung volumes receiving above various dose levels were obtained in addition to V20Gy and Dmean. These dosimetric parameters and patient characteristics were evaluated with univariate and multivariate logistic regression tests. Receiver operating characteristic curves were generated to obtain the optimal dosimetric constraints through analyzing RP and non-RP sensitivity and specificity values. Results: The multivariate analysis showed V40Gy and Dmean to be statistically significant for proton and photon patients, respectively. V35Gy to V50Gy were strongly correlated to V40Gy for proton patients. Based on the receiver operating characteristic curves, V35Gy to V50Gy had the highest area under the curve compared with other dose levels for proton patients. A potential dosimetric constraint for RP predictor in proton patients is V40Gy ≤ 23%. Conclusions: In addition to V20Gy and Dmean, the lung volume receiving higher doses, such as V40Gy, may be used as an additional indicator for RP in LA-NSCLC patients treated with proton therapy.

The identity of catalytic sites for H2O2 generation in carbon-based materials remains controversial with limited experimental evidence to date. Here, the authors decorate various target functional groups on carbon materials and quinone-enriched samples exhibit the highest activity and selectivity.

In this work, worm-like SnS2 nanoparticles were prepared by a hydrothermal process. And then their photocatalytic activity was explored for the restoration of effluent containing Cr (VI). The results indicate that the product obtained is hexagonal SnS2 nanoparticles and adopts a worm-like morphology with length of approximate 6 nm and diameter of 3 nm. Moreover, the as-prepared SnS2 nanoparticles possess high photocatalytic activity for the visible light-driven reduction of Cr (VI). When the concentration of Cr (VI) is 4 × 10−4 mol/L, 99% Cr (VI) can be reduced over the as-prepared SnS2 nanoparticles within 30 min under visible irradiation.

Acupuncture is widely used in the treatment of cerebral hemorrhage, and it improves outcomes in experimental animal models and patients. However, the mechanisms underlying the effectiveness of acupuncture treatment for cerebral hemorrhage are still unclear. In this study, a model of intracerebral hemorrhage was produced by injecting 50 μL autologous blood into the caudate nucleus in Wistar rats. Acupuncture at Baihui (DU20) and Qubin (GB7) acupoints was performed at a depth of 1.0 inch, 12 hours after blood injection, once every 24 hours. The needle was rotated at 200 r/min for 5 minutes, For each 30-minute session, needling at 200 r/min was performed for three sessions, each lasting 5 minutes. For the positive control group, at 6 hours, and 1, 2, 3 and 7 days after induction of hemorrhage, the rats were intraperitoneally injected with 1 mL aniracetam (0.75 mg/mL), three times a day. The Bederson behavioral test was used to assess palsy in the contralateral limbs. Western blot assay was used to examine the expression levels of Nestin and basic fibroblast growth factor in the basal ganglia. Immunohistochemistry was performed to count the number of Nestin- and glial cell line-derived neurotrophic factor-positive cells in the basal ganglia. Acupuncture effectively reduced hemorrhage and brain edema, elevated the expression levels of Nestin and basic fibroblast growth factor in the basal ganglia, and increased the number of Nestin- and glial cell line-derived neurotrophic factor-positive cells in the basal ganglia. Together, these findings suggest that acupuncture promotes functional recovery after cerebral hemorrhage by increasing the expression of neurotrophic factors. The study was approved by the Committee for Experimental Animals of Heilongjiang Medical Laboratory Animal Center (approval No. 2017061001) on June 10, 2017.

Low dimensional lead halide perovskites possess intriguing optical properties that are still under debate. Here Cui et al. use hydrogen bonds containing spacers to synthesize highly luminescent perovskites with fully isolated lead-bromide octahedras and shed light on the origin of the emission.

To study the effect of scalp acupuncture (SA) on the mitophagy signaling pathway in the caudate nucleus of Sprague-Dawley rats following intracerebral hemorrhage (ICH). An ICH model was established by injecting autologous arterial blood into the caudate nucleus in 200 male Sprague-Dawley rats, which were divided into five groups: sham, ICH, 3-methyladenine group (3-MA, 30 mg/kg), SA, and SA+3-MA. Animals were analyzed at 6 and 24 h as well as at 3 and 7 days. Composite neurological scale score was significantly higher in the SA group than in the ICH group. Transmission electron microscopy showed less structural damage and more autophagic vacuoles within brain in the SA group than in the ICH group. SA group showed higher levels of Beclin1, Parkin, PINK1, NIX protein, and a lower level of Caspase-9 in brain tissue. These animals consequently showed less neural cell apoptosis. Compared with the SA group, however, the neural function score and levels of mitophagy protein in the SA+3-MA group were decreased, neural cell apoptosis was increased with more severe structural damage, which suggested that 3-MA may antagonize the protective effect of SA on brain in rats with ICH. SA may mitigate the neurologic impairment after ICH by enhancing mitophagy and reducing apoptosis.

The kidneys are a pair of important organs that excretes endogenous waste and exogenous biological agents from the body. Numerous transporters are involved in the excretion process. The levels of these transporters could affect the pharmacokinetics of many drugs, such as organic anion drugs, organic cationic drugs, and peptide drugs. Eleven drug transporters in the kidney (OAT1, OAT3, OATP4C1, OCT2, MDR1, BCRP, MATE1, MATE2-K, OAT4, MRP2, and MRP4) have become necessary research items in the development of innovative drugs. However, the levels of these transporters vary between different species, sex-genders, ages, and disease statuses, which may lead to different pharmacokinetics of drugs. Here, we review the differences of the important transports in the mentioned conditions, in order to help clinicians to improve clinical prescriptions for patients. To predict drug-drug interactions (DDIs) caused by renal drug transporters, the molecular docking method is used for rapid screening of substrates or inhibitors of the drug transporters. Here, we review a large number of natural products that represent potential substrates and/or inhibitors of transporters by the molecular docking method.