Pharmacological vitamin C inhibits mTOR signaling and tumor growth by degrading Rictor and inducing HMOX1 expression.

Pharmacological vitamin C (VC) is a potential natural compound for cancer treatment. However, the mechanism underlying its antitumor effects remains unclear. In this study, we found that pharmacological VC significantly inhibits the mTOR (including mTORC1 and mTORC2) pathway activation and promotes GSK3-FBXW7-mediated Rictor ubiquitination and degradation by increasing the cellular ROS. Moreover, we identified that HMOX1 is a checkpoint for pharmacological-VC-mediated mTOR inactivation, and the deletion of FBXW7 or HMOX1 suppresses the regulation of pharmacological VC on mTOR activation, cell size, cell viability, and autophagy. More importantly, it was observed that the inhibition of mTOR by pharmacological VC supplementation in vivo produces positive therapeutic responses in tumor growth, while HMOX1 deficiency rescues the inhibitory effect of pharmacological VC on tumor growth. These results demonstrate that VC influences cellular activities and tumor growth by inhibiting the mTOR pathway through Rictor and HMOX1, which may have therapeutic potential for cancer treatment.

Boosting Osmotic Energy Harvesting from Organic Solutions by Ultrathin Covalent Organic Framework Membranes.

Extracting osmotic energy from waste organic solutions via reverse electrodialysis represents a promising approach to reuse such industrial wastes and helps to mitigate the ever-growing energy needs. Herein, a molecularly thin membrane of covalent organic frameworks is engineered via interfacial polymerization to investigate its ion transport behavior in organic solutions. Interestingly, a significant deviation from linearity between ion conductance and reciprocal viscosity is observed, attributed to the nanoscale confinement effect on intermolecular interactions. This finding suggests a potential strategy to modulate the influence of apprarent viscosity on transmembrane transport. The osmotic energy harvesting of the ultrathin membrane in organic systems was studied, achieving an unprecedented output power density of over 84.5 W m-2 at a 1000-fold salinity gradient with a benign conversion efficiency and excellent stability. These findings provide a meaningful stepping stone for future studies seeking to fully leverage the potentials of organic systems in energy harvesting applications.

Microporous Polyelectrolyte Complexes by Hydroplastic Foaming.

Polyelectrolyte complexes (PECs) have emerged as an attractive category of materials for their water processability and some similarities to natural biopolymers. Herein, we employ the intrinsic hydroplasticity of PEC materials to enable the generation of porous structures with the aid of gas foaming. Such foamable materials are fabricated by simply mixing polycation, polyanion, and a UV-initiated chemical foaming agent in an aqueous solution, followed by molding into thin films. The gas foaming of the PEC films can be achieved upon exposure to UV illumination under water, where the films are plasticized and the gaseous products from the photolysis of foaming agents afford the formation, expanding, and merging of numerous bubbles. The porosity and morphology of the resulting porous films can be customized by tuning film composition, foaming conditions, and especially the degree of plasticizing effect, illustrating the high flexibility of this hydroplastic foaming method. Due to the rapid initiation of gas foaming, the present method enables the formation of porous structures via an instant one-step process, much more efficient than those existing strategies for porous PEC materials. More importantly, such a pore-forming mechanism might be extended to other hydroplastic materials (e.g., biopolymers) and help to yield hydroplasticity-based processing strategies.

Clinical features and viral load variations of Mpox: a retrospective study in Chongqing, China.

PURPOSE: Since May 2022, Mpox has spread extensively outside of Africa, posing a serious threat to the health of people globally, and particularly to the men who have sex with men (MSM) population. Chongqing, a province in Southwest China, has relatively large MSM and people living with HIV (PLWH) populations, presenting conditions conducive to the wide dissemination of Mpox. In this study, we investigated the clinical characteristics of Mpox patients among MSM and PLWH in Chongqing, aiming to inform the development of targeted prevention, control, and treatment strategies for Mpox. METHOD: We evaluated the clinical characteristics, travel history, time of onset, distribution and number of skin lesions of Mpox patients admitted to the Chongqing Public Health Medical Center between September 2022 and October 2023. Meanwhile, a series of clinical samples were collected and the pathogen of interest was identified as Mpox virus using quantitative polymerase chain reaction (qPCR). The results were presented in the form of cycle thresholds (Ct), which help to approximate the quantification of viral load. RESULTS: As of October 11, 2023, the Chongqing Public Health Medical Center reported a total of nine Mpox virus infections. All the patients identified were male and belonged to the MSM population, among whom seven (77.8%) were living with HIV, and maintained a preserved immune system while achieving viral suppression via effective ART. We observed no discernible clinical differences between MSM with Mpox with or without HIV, and no fatalities were recorded. Viral loads were observed to be higher in samples taken from the skin than those from the throat, nasopharynx, blood, or semen. CONCLUSION: In this retrospective study, the clinical manifestations of MPXV infection appeared consistent among MSM patients, regardless of HIV status. Elevated MPXV viral loads in the skin and mucosal tissues, particularly at genital and anal sites, indicate that transmission is more likely to occur via direct physical contact as opposed to respiratory pathways or through exposure to bodily fluids.

Nomogram to Predict Good Collateral Formation After the STA-MCA Bypass Surgery in Adult Patients With Moyamoya Disease.

BACKGROUND: Collateral formation from the extracranial carotid artery to ischemic brain tissue determines the clinical success of superficial temporal artery (STA) to middle cerebral artery (MCA) bypass surgery in adult patients with moyamoya disease, but postoperative collateral formation (PCF) after STA-MCA bypass surgery is unpredictable. Accurate preoperative prediction of acceptable PCF could improve patient selection. This study aims to develop a prediction nomogram model for PCF in this patient population. METHODS: Adult patients with moyamoya disease undergoing the STA-MCA bypass surgery between January 2013 and December 2020 at a single institution were retrospectively or prospectively enrolled in this observational study. Data including potential clinical and radiological predictors were obtained from hospital records. A nomogram was generated based on a multivariate logistic regression analysis, to identify potential predictors associated with good PCF. The performance of the nomogram was evaluated for discrimination, calibration, and clinical utility. RESULTS: Data from 243 patients with moyamoya disease who underwent the STA-MCA bypass surgery were analyzed to build the nomogram. After 1-year follow-up, 162 (66.7%) hemispheres had good PCF and 81 (33.3%) had poor PCF. Good PCF is associated with 3 preoperative factors: age at operation, a diameter of donor branch of STA, and the preinfarction period stage. Incorporating these 3 factors, the model achieved a concordance index of 0.88 (95% CI, 0.84-0.92) and had a well-fitted calibration curve and good clinical application value. A cutoff value of 100 was determined to predict good PCF via this nomogram. CONCLUSIONS: The nomogram exhibits high accuracy in predicting good PCF after the STA-MCA bypass surgery in adult patients with moyamoya disease and may allow surgeons to better evaluate preoperatively candidacy for successful bypass surgery.

Two-Dimensional Nanofluidic Membranes with Intercalated In-Plane Shortcuts for High-Performance Blue Energy Harvesting.

Two-dimensional nanofluidic membranes offer great opportunities for developing efficient and robust devices for ionic/water-nexus energy harvesting. However, low counterion concentration and long pathway through limited ionic flux restrict their output performance. Herein, it is demonstrated that rapid diffusion kinetics can be realized in two-dimensional nanofluidic membranes by introducing in-plane holes across nanosheets, which not only increase counterion concentration but also shorten pathway length through the membranes. Thus, the holey membranes exhibited an enhanced performance relative to the pristine ones in terms of osmotic energy conversion. In particular, a biomimetic multilayered membrane sequentially assembled from pristine and holey sections offers an optimized combination of selectivity and permeability, therefore generating a power density up to 6.78 W m-2 by mixing seawater and river water, superior to the majority of the state-of-the-art lamellar nanofluidic membranes. This work highlights the importance of channel morphologies and presents a general strategy for effectively improving ion transport through lamellar membranes for high-performance nanofluidic devices.

Rictor mediates p53 deactivation to facilitate the malignant transformation of hepatocytes and promote hepatocarcinogenesis.

BACKGROUND: Mutations in TP53 gene is considered a main driver of hepatocellular carcinoma (HCC). While TP53 mutations are the leading cause of p53 dysfunction, their occurrence rates may drop to approximately 10% in cohorts without hepatitis B virus and aflatoxin exposure. This observation suggests that the deactivation of wild-type p53 (p53wt) may be a critical factor in the majority of HCC cases. However, the mechanism undermining p53wt activity in the liver remains unclear. METHODS: Microarray analysis and luciferase assay were utilized to confirm target associations. Gain- and/or loss-of-function methods were employed to assess alterations in signaling pathways. Protein interactions were analyzed by molecular immunological methods and further visualized by confocal microscopy. Bioinformatic analysis was performed to analyze clinical significance. Tumor xenograft nude mice were used to validate the findings in vivo. RESULTS: Our study highlights the oncogenic role of Rictor, a key component of the mammalian target of rapamycin complex 2 (mTORC2), in hepatocytes. Rictor exerts its oncogenic function by binding to p53wt and subsequently blocking p53wt activity based on p53 status, requiring the involvement of mTOR. Moreover, we observed a dynamic nucleocytoplasmic distribution pattern of Rictor, characterized by its translocation from the nucleus (in precancerous lesions) to the cytoplasm (in HCCs) during malignant transformation. Notably, Rictor is directly targeted by the liver-enriched microRNA miR-192, and the disruption of the miR-192-Rictor-p53-miR-192 signaling axis was consistently observed in both human and rat HCC models. Clinical analysis associated lower miR-192/higher Rictor with shorter overall survival and more advanced clinical stages (P < 0.05). In mice, xenograft tumors overexpressing miR-192 exhibited lower Rictor expression levels, leading to higher p53 activity, and these tumors displayed slower growth compared to untreated HCC cells. CONCLUSIONS: Rictor dynamically shuttles between the nucleus and cytoplasm during HCC development. Its pivotal oncogenic role involves binding and inhibiting p53wt activity within the nucleus in early hepatocarcinogenesis. Targeting Rictor presents a promising strategy for HCC based on p53 status.

Resveratrol Promotes Gluconeogenesis by Inhibiting SESN2-mTORC2-AKT Pathway in Calf Hepatocytes.

BACKGROUND: The glucose requirement of dairy cows is mainly met by increasing the rate of hepatic gluconeogenesis. However, due to negative energy balance, the liver of periparturient cows is under oxidative stress induced by lipid over-mobilization, and hepatic gluconeogenesis is reduced. Studies have demonstrated that resveratrol, which is widely known for its antioxidant properties, can alter hepatic gluconeogenesis. However, it is not clear whether resveratrol could regulate hepatic gluconeogenesis by its antioxidant properties. OBJECTIVES: This study aims to investigate the precise effect of resveratrol in hepatic gluconeogenesis, the role of resveratrol on hydrogen peroxide (H2O2)-induced oxidative stress in hepatocytes and the potential mechanism using primary hepatocytes. METHODS: Primary hepatocytes were isolated from 5 healthy Holstein calves (1 d old, 30 to 40 kg, fasted) and treated with different concentrations of resveratrol (0, 5, 10, 25, or 50 µM) combined with or without H2O2 (0, 100, or 200 µM) induction for 12 h. RESULTS: Resveratrol enhanced the expression of gluconeogenic genes of calf hepatocytes in a dose-dependent manner (P < 0.05). Conversely, H2O2 suppressed the expression of gluconeogenic genes and induced oxidative stress (P < 0.05), which was improved by resveratrol in calf hepatocytes (P < 0.001). Furthermore, the mechanistic target of rapamycin complex 2 (mTORC2)-AKT pathway was found to negatively regulate gluconeogenesis. An AKT inhibitor was used to assess the role of the mTORC2-AKT pathway in the effects of resveratrol. The results showed resveratrol promoted hepatic gluconeogenesis by inhibiting the mTORC2-AKT pathway. Moreover, sestrin 2 (SESN2) upregulated the activity of mTORC2. We further found that resveratrol decreased SESN2 levels (P < 0.001). CONCLUSIONS: This study indicated that resveratrol enhances the gluconeogenic capacity of calf hepatocytes by improving H2O2-induced oxidative stress and modulating the activity of the SESN2-mTORC2-AKT pathway, implying that resveratrol may be a promising target for ameliorating liver oxidative stress in transition cows.

The role of pyroptosis in incomplete immune reconstitution among people living with HIV：Potential therapeutic targets.

Globally, HIV infection causes significant morbidity and mortality, and is a major public health problem. Despite the fact that widespread use of antiretroviral therapy (ART) has substantially altered the natural history of HIV infection from originally being a universally lethal disease to now being a chronic medical condition for those taking appropriate treatment, approximately 10-40% of people living with HIV (PLWH) who take effective ART and maintain long-term viral suppression fail to achieve normalization of CD4 + T-cell counts. This phenomenon is referred to as incomplete immune reconstitution or immunological non-response. Although the precise mechanisms underlying this outcome have not been elucidated, recent evidence indicates that excessive pyroptosis may play a crucial role in the development of incomplete immune reconstitution. Pyroptosis is characterized by the formation of pores in the cell membrane, cell rupture, and secretion of intracellular contents and pro-inflammatory cytokines, including IL-1ß and IL-18. This excessive inflammation-induced programmed cell death leads to a massive loss of CD4 + T-cells, and inflammatory consequences that may promote and sustain incomplete immune reconstitution. Herein, we review the possible pathways activated in HIV infection by inflammasomes that act as switches of pyroptosis, and the role of pyroptosis in HIV, as well as the relevance of CD4 + T-cells in incomplete immune reconstitution. We also highlight the possible mechanisms of pyroptosis involved in incomplete immune reconstitution, thus paving the way for the development of potential targets for the treatment of incomplete immune reconstitution.

CT hyperdense lesions after endovascular therapy in acute ischemic stroke: imaging findings and clinical significance.

Background The hyperdense lesion on non-contrast CT (NCCT) is a common postoperative phenomenon in acute ischemic stroke (AIS) patients who are treated with endovascular therapy (EVT). Both contrast extravasation and hemorrhagic transformation presented hyperdense lesions on NCCT, which are sometimes difficult to distinguish them. Summary of Review Radiographic findings are important for identifying contrast extravasation and hemorrhagic transformation. We recommended a standardized follow-up protocol involving imaging and clinical evaluation as it will allow neurologists and neuroradiologists to reveal the relationships between these hyperdensities and various clinical outcomes. Key Messages Dual-energy CT and susceptibility weighted imaging are capable of distinguishing contrast extravasation and hemorrhagic transformation at an early stage after EVT. However, in institutions without access to such technology, a follow-up protocol based on NCCT is crucial.

Angiographic and Hemodynamic Features in Asymptomatic Hemispheres of Patients With Moyamoya Disease.

BACKGROUND AND PURPOSE: There is also a risk of stroke in the asymptomatic hemispheres of moyamoya disease (MMD), but it does not draw enough attention. The study investigated the differences between the three types of asymptomatic hemispheres in MMD and their associations with the two types of symptomatic hemispheres, respectively. METHODS: Retrospectively reviewed clinical and imaging characteristics of asymptomatic and symptomatic hemispheres in consecutive cases of single-center MMD patients, with an emphasis on imaging characterization regarding vascular morphology and cerebral perfusion. MMD hemispheres were categorized into 5 types: hemorrhagic hemispheres, ischemic hemispheres, asymptomatic hemispheres in unilateral hemorrhagic MMD, asymptomatic hemispheres in unilateral ischemic MMD, and bilateral asymptomatic hemispheres in MMD. Angiographic feature was assessed by Suzuki's angiographic stage, while hemodynamic feature was assessed by preinfarction period stage. RESULTS: One hundred ninety-four MMD patients with 388 hemispheres were enrolled. Asymptomatic hemispheres in unilateral hemorrhagic MMD were largely similar to hemorrhagic hemispheres, both had more advanced Suzuki's angiographic stage and lower degree of hemodynamic failure compared with bilateral asymptomatic hemispheres in MMD and asymptomatic hemispheres in unilateral ischemic MMD. Asymptomatic hemispheres in unilateral ischemic MMD were similar to ischemic hemispheres, both had less advanced Suzuki's angiographic stage and higher degree of hemodynamic failure compared with bilateral asymptomatic hemispheres in MMD and asymptomatic hemispheres in unilateral hemorrhagic MMD. Bilateral asymptomatic hemispheres in MMD were different from the other hemispheres and had less advanced Suzuki's angiographic stage and lower degree of hemodynamic failure. CONCLUSIONS: The three types of asymptomatic hemispheres in MMD are defined and have unique angiographic and hemodynamic features. Different combinations of the two features can reflect the tendency of pathological evolution in these different asymptomatic hemispheres.

Unilateral biportal endoscopic decompression for symptomatic thoracic ossification of the ligamentum flavum: a case control study.

PURPOSE: Thoracic ossification of the ligamentum flavum (OLF) is an uncommon disease that mostly occurs in East Asians. Laminectomy is often considered when patients develop neuro-related symptoms but may associate with treatment-related complications. This study aimed to evaluate the efficacy and safety of unilateral biportal endoscopic (UBE) decompression treatment in patients with symptomatic OLF. METHODS: From January 2020 to January 2021, patients with spinal cord compression symptoms and imaging-defined single-level thoracic OLF were enrolled in this study and received UBE decompression treatment. Their pre- and postoperative neurological statuses were evaluated by the modified Japanese Orthopaedic Association (mJOA) score, Visual Analog Scale (VAS) for leg pain, and Frankel grade. RESULTS: Fourteen patients with an average age of 59.4 years were enrolled in the study. The mean operation time was 66.1 ± 15.4 minutes. Patients were followed up for at least one year after receiving the treatment. Our data suggested that their mJOA score (preop 6.2 ± 1.2, 1 year 8.5 ± 0.9; P < 0.001) and VAS score (preop 4.5 ± 2.0, 1 year 0.5 ± 0.9; P < 0.001) were significantly improved compared with that before operation. Cerebrospinal fluid leakage occurred in one patient, head and neck pain occurred in two patients, and hyperalgesia of lower limbs occurred in two patients. All these complications did not cause serious consequences. CONCLUSION: This primary study indicated that the UBE decompression treatment can achieve satisfactory clinical results in patients with thoracic OLF at single level and provide an alternative treatment option.

Integration of a pure moving bed biofilm reactor process into a large micro-polluted water treatment plant.

The pure-MBBR process was applied to remove ammonia in a full-scale micro-polluted-water treatment plant with a daily treatment capacity of 260 × 104 m3/d, Guangdong, China. The relationship between treatment efficiency, physical and chemical properties and microbial diversity in the process of biofilm growth was explored, and the oxygen transfer model of biofilm was established. The results show that the effluent of two-stage pure MBBR process is stable and up to standard after 10 days' incubation. The nitrification loads of two-stage biofilm was stable on the 14th day. The biomass and biofilm thickness lagged behind the nitrification load, and reached a relatively stable level on the 28th day. The species richness of biofilm basically reached a stable level on the 21st day, and the microbial diversity of primary biofilm was higher. In the primary and secondary stage at different periods, the relative abundance of dominant nitrifying bacteria Nitrospira reaches 8.48-13.60%, 6.48-9.27%, and Nitrosomonas reaches 2.89-5.64%, 0.00-3.48%. The pure MBBR system mainly adopts perforated aeration. Through the cutting and blocking of bubbles by suspended carriers, the oxygen transfer rate of the system was greatly improved.

[Impact of Cadmium on the expressions of piRNAs in the rat testis].

OBJECTIVE: To study the impact of cadmium (Cd) on the expressions of PIWI-interacting RNAs (piRNA) in the rat testis and its possible action mechanism. METHODS: Twelve 6-week-old SD rats were randomly divided into a Cd-exposure and a control group, the former gavaged with CdCl2 at 3 mg/kg/d and the latter with normal saline, all for 28 successive days. Then the testicular tissues were collected from the rats, sperm concentration and motility were obtained by computer-assisted sperm analysis (CASA), and piRNA sequencing was performed using the gene chip, followed by bioinformatics analysis of differentially expressed piRNAs. RESULTS: Compared with the controls, the rats in the Cd-exposure group showed significantly decreased sperm concentration and motility (P < 0.05). The expressions of 272 piRNAs were up-regulated and 402 down-regulated after 28 days of Cd exposure, and 4 of the up-regulated piRNAs were consistent with the results of gene chip verification. Bioinformatics analysis showed that the 4 up-regulated piRNA target genes were involved in 50 biological processes, such as negative regulation of apoptosis, positive regulation of gene expression and positive regulation of GTPase activity, and mainly concentrated in 13 signaling pathways including transcription dysregulation, calcium and mitogen-activated protein kinase signaling pathways in cancer. Among them, PIRNA-DQ765261 had a binding site with Bcl-2. CONCLUSION: Cadmium can induce changes in the expressions piRNAs in the rat testicular tissue, and some piRNAs may be involved in the autophagy and apoptosis of sperm. Bcl-2 may be the target of PIRNA-DQ765261.

CD205+ polymorphonuclear myeloid-derived suppressor cells suppress antitumor immunity by overexpressing GLUT3.

Myeloid-derived suppressor cells (MDSCs) are responsible for antitumor immunodeficiency in tumor-bearing hosts. Primarily, MDSCs are classified into 2 groups: monocytic (M)-MDSCs and polymorphonuclear (PMN)-MDSCs. In most cancers, PMN-MDSCs (CD11b+ Ly6Clow Ly6G+ cells) represent the most abundant MDSC subpopulation. However, the functional and phenotypic heterogeneities of PMN-MDSC remain elusive, which delays clinical therapeutic targeting decisions. In the 4T1 murine tumor model, CD11b+ Ly6Glow PMN-MDSCs were sensitive to surgical and pharmacological interventions. By comprehensively analyzing 64 myeloid cell-related surface molecule expression profiles, cell density, nuclear morphology, and immunosuppressive activity, the PMN-MDSC population was further classified as CD11b+ Ly6Glow CD205+ and CD11b+ Ly6Ghigh TLR2+ subpopulations. The dichotomy of PMN-MDSCs based on CD205 and TLR2 is observed in 4T07 murine tumor models (but not in EMT6). Furthermore, CD11b+ Ly6Glow CD205+ cells massively accumulated at the spleen and liver of tumor-bearing mice, and their abundance correlated with in situ tumor burdens (with or without intervention). Moreover, we demonstrated that CD11b+ Ly6Glow CD205+ cells were sensitive to glucose deficiency and 2-deoxy-d-glucose (2DG) treatment. Glucose transporter 3 (GLUT3) knockdown by siRNA significantly triggered apoptosis and reduced glucose uptake in CD11b+ Ly6Glow CD205+ cells, demonstrating the dependence of CD205+ PMN-MDSCs survival on both glucose uptake and GLUT3 overexpression. As GLUT3 has been recognized as a target for the rescue of host antitumor immunity, our results further directed the PMN-MDSC subsets into the CD205+ GLUT3+ subpopulation as future targeting therapy.

Intensive versus guideline-recommended blood pressure reduction in acute lacunar stroke with intravenous thrombolysis therapy: The ENCHANTED trial.

BACKGROUND AND PURPOSE: This was an investigation of the differential effects of early intensive versus guideline-recommended blood pressure (BP) lowering between lacunar and non-lacunar acute ischaemic stroke (AIS) in the BP arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS: In 1,632 participants classified as having definite or probable lacunar (n = 454 [27.8%]) or non-lacunar AIS according to pre-specified definitions based upon clinical and adjudicated imaging findings, mean BP changes over days 0-7 were plotted, and systolic BP differences by treatment between subgroups were estimated in generalized linear models. Logistic regression models were used to estimate the BP treatment effects on 90-day outcomes (primary, an ordinal shift of modified Rankin scale scores) across lacunar and non-lacunar AIS after adjustment for baseline covariables. RESULTS: Most baseline characteristics, acute BP and other management differed between lacunar and non-lacunar AIS, but mean systolic BP differences by treatment were comparable at each time point (all pinteraction  > 0.12) and over 24 h post-randomization (-5.5, 95% CI -6.5, -4.4 mmHg in lacunar AIS vs. -5.6, 95% CI -6.3, -4.8 mmHg in non-lacunar AIS, pinteraction  = 0.93). The neutral effect of intensive BP lowering on functional outcome and the beneficial effect on intracranial haemorrhage were similar for the two subgroups (all pinteraction  > 0.19). CONCLUSIONS: There were no differences in the treatment effect of early intensive versus guideline-recommended BP lowering across lacunar and non-lacunar AIS.

Traditional Chinese medicine symptom normalization approach leveraging hierarchical semantic information and text matching with attention mechanism.

Traditional Chinese medicine (TCM) symptom normalization is difficult because the challenges of the symptoms having different literal descriptions, one-to-many symptom descriptions and different symptoms sharing a similar literal description. We propose a novel two-step approach utilizing hierarchical semantic information that represents the functional characteristics of symptoms and develop a text matching model that integrates hierarchical semantic information with an attention mechanism to solve these problems. In this study, we constructed a symptom normalization dataset and a TCM normalization symptom dictionary containing normalization symptom words, and assigned symptoms into 24 classes of functional characteristics. First, we built a multi-label text classifier to isolate the hierarchical semantic information from each symptom description and count the corresponding normalization symptoms and filter the candidate set. Then we designed a text matching model of mixed multi-granularity language features with an attention mechanism that utilizes the hierarchical semantic information to calculate the matching score between the symptom description and the normalization symptom words. We compared our approach with other baselines on real-world data. Our approach gives the best performance with a Hit@ 1, 3, and 10 of 0.821, 0.953, and 0.993, respectively, and a MeanRank of 1.596, thus outperforming significantly regarding the symptom normalization task. We developed an approach for the TCM symptom normalization task and demonstrated its superior performance compared with other baselines, indicating the promise of this research direction.

Shikonin relieves osteoporosis of ovariectomized mice by inhibiting RANKL-induced NF-κB and NFAT pathways.

Postmenopausal osteoporosis is very common in women. Currently, many kinds of new drugs are being developed for this disease. Postmenopausal osteoporosis is closely related to overactivity of osteoclasts in body. Shikonin is purple red naphthoquinone pigment extracted from lithospermum, which has anti-inflammation, antivirus, anticancer and other bioactivities. At the same time, it has been proved that shikonin can promote the proliferation and differentiation of osteoblasts, but its influence on osteoclasts and molecular mechanism are unknown. Our study showed that shikonin could inhibit the activity and formation of RANKL-mediated osteoclasts depending on dose without affecting the activity of bone marrow macrophages (BMM). In addition, we have also found that shikonin can inhibit the expression of specific marker gene of osteoclasts, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), cathepsin K (Ctsk), tartrate resistant acid phosphatase (TRAcP) and calcitonin receptor. Shikonin also could promote the proliferation of MC3T3-E1, increasing the expression of mRNA related to osteogenesis, like the expression of bone morphogenetic protein-2 (BMP-2), alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2) and osteocalcin (OCN). Luciferase reporter gene assay and Western blot analysis further indicated that shikonin could inhibit the activity of RANKL-induced NF-κB and NFAT receptors. Moreover, shikonin can also slow down bone loss of ovariectomized (OVX) mice by inhibiting the activity of osteoclasts. This work explains the molecular mechanism of shikonin in RANKL-mediated formation of osteoclasts, and reveals the potential of further developing shikonin into a new drug for prevention and treatment of postmenopausal osteoporosis.

A method for separation and purification of mouse splenocytes by density gradient centrifugation.

Spleen is an information-rich and easy-accessible peripheral lymphoid organ. It has complex cell composition because of the immunocytes maturity and settle down. Changes of the composition and function of these immunocytes are critical to body immune response. To understand the cell behaviors, specific cell subpopulations are required to be separated without heterogeneity. Density gradient centrifugation is one of the cell separation methods with high throughput. However, the greatest defect of this method is its low cell purity. In this study, the separation conditions of tumor-bearing mouse splenocytes were optimized by separation solutions with different density gradients. After separation, lymphocytes were located at the second layer with the proportion of 84.9%, monocytic-like myeloid-derived suppressor cells (Mo-MDSCs) were located at the fourth layer with the proportion of 54.2% and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) were located at the sixth layer with the proportion of 85.5%. Cells in different layers were further determined by verifying the gene expression pattern of some chemokine receptors on cell surfaces. Furthermore, this method was also used to separate healthy mouse splenocytes. Therefore, this method will be highly useful to separate mouse splenocytes and has laid a foundation for further research on the changes and roles of immunocytes during the development of cancer.

Tissue-specific transcriptomic profiling of Plantago major provides insights for the involvement of vasculature in phosphate deficiency responses.

The vasculature of higher plants is important with transport of both nutrient and information molecules. To understand the correspondence of this tissue in molecular responses under phosphate (Pi) deficiency, Plantago major, a model plant for vasculature biology study, was chosen in our analysis. After RNA-Seq and de novo transcriptome assembly of 24 libraries prepared from the vasculature of P. major, 37,309 unigenes with a mean length of 1571 base pairs were obtained. Upon 24 h of Pi deficiency, 237 genes were shown to be differentially expressed in the vasculature of P. major. Among these genes, only 27 have been previously identified to be specifically expressed in the vasculature tissues in other plant species. Temporal expression of several marker genes associated with Pi deficiency showed that the time period of first 24 h is at the beginning stage of more dynamic expression patterns. In this study, we found several physiological processes, e.g., "phosphate metabolism and remobilization", "sucrose metabolism, loading and synthesis", "plant hormone metabolism and signal transduction", "transcription factors", and "metabolism of other minerals", were mainly involved in early responses to Pi deficiency in the vasculature. A number of vasculature genes with promising roles in Pi deficiency adaptation have been identified and deserve further functional characterization. This study clearly demonstrated that plant vasculature is actively involved in Pi deficiency responses and understanding of this process may help to create plants proficient to offset Pi deficiency.