Self-Adaptive Macroscale Superlubricity Based on the Tribocatalytic Properties of Partially Oxidized Black Phosphorus.

The high-flash heat generated by direct contact at asperity tips under high contact stress and shear significantly promotes the tribocatalytic reaction between a lubricating medium and a friction interface. Macroscale superlubricity can be achieved by using additives with good lubrication properties to promote the decomposition and transformation of a lubricating medium to form an ultralow shear interface during the friction process. This paper proposed a way to achieve self-adaptive oil-based macroscale superlubricity on different tribopairs, including steel-steel and steel-DLC (diamond-like carbon), which is based on the excellent lubricating performance of black phosphorus with active oxidation and the catalytic cleavage behavior of oil molecules on the surface of oBP. This work potentially expands the industrial application of superlubricity.

Maternal SMC2 is essential for embryonic development via participating chromosome condensation in mice.

During the oocyte growth, maturation and zygote development, chromatin structure keeps changing to regulate different nuclear activities. Here, we reported the role of SMC2, a core component of condensin complex, in oocyte and embryo development. Oocyte-specific conditional knockout of SMC2 caused female infertility. In the absence of SMC2, oocyte meiotic maturation and ovulation occurred normally, but chromosome condensation showed defects and DNA damages were accumulated in oocytes. The pronuclei were abnormally organized and micronuclei were frequently observed in fertilized eggs, their activity was impaired, and embryo development was arrested at the one-cell stage, suggesting that maternal SMC2 is essential for embryonic development.

Development and investigation of a novel device with gemcitabine for hyperthermic intravesical chemotherapy.

PURPOSE: To evaluate the safety and efficacy of a novel hyperthermic intravesical chemotherapy (HIVEC) device in combination with gemcitabine. MATERIALS AND METHODS: A pilot clinical trial was performed on patients with high-risk non-muscle invasive bladder cancer (NMIBC), who received HIVEC via the novel device (BR-PRG). Treatment regimen included eight weekly instillations of intravesical GEM (3 g in 150 mL normal saline [NS]) at a temperature of 45 °C for 60 min. Assessment of adverse events (AEs) was the primary objective of the trial. Disease recurrence and the thermal stability of GEM were also analyzed. RESULTS: A total of 116 HIVEC treatments were delivered. Fifteen and eighteen patients were included in the effectiveness and safety analysis, respectively. Median follow-up was 12 months; five patients experienced a disease recurrence. One-year cumulative incidence of recurrence was 23.8% in EORTC intermediate risk group and 37.5% in high-risk group. Ten patients experienced at least one AE, with the most common being acute urinary tract infection, followed by urinary tract pain, and hematuria. Two patients experienced acute cystitis (grade 3 AE) and instillations were postponed until full recovery. Other AEs were minor, and no systemic toxicity was observed. The contents of GEM in solution of 0.9% NS or NS mixed with artificial urine were stable at 25 °C, 37 °C, 43 °C, 45 °C, 47 °C and 50 °C for 2 h. CONCLUSION: GEM can be an ideal drug for use in HIVEC due to its good thermal stability. BR-PRG, combined with GEM was safe and effective in administering HIVEC.

Discovery and preclinical evaluations of JBD0131, a novel nitrodihydro-imidazooxazole anti-tuberculosis agent.

Multidrug-resistant pulmonary tuberculosis (MDR-TB) is a major health problem worldwide. The treatment for MDR-TB requires medications for a long duration (up to 20-24 months) with second-line drugs resulting in unfavorable outcomes. Nitroimidazoles are promising antimycobacterial agents known to inhibit both aerobic and anaerobic mycobacterial activity. Delamanid and pretomanid are two nitroimidazoles approved by the regulatory agencies for MDR-TB treatment. However, both agents possess unsatisfactory absorption and QTc prolongation. In our search for a safer nitroimidazole, we discovered JBD0131 (2). It exhibited excellent anti-mycobacterial activity against M. tuberculosis H37Rv in vitro and in vivo, improved PK and absorption, reduced QT prolongation potential of delamanid. JBD0131 is currently in clinical development in China for pulmonary tuberculosis (CTR20202308).

Rapid response to secukinumab in a 5-year-old with deficiency of the interleukin-36 receptor antagonist (DITRA) with severe scalp and nail involvement.

Deficiency of the interleukin-36 receptor antagonist (DITRA) is an autosomal recessive disease caused by mutations of the IL36RN gene. DITRA is characterized by acute generalized pustular psoriasis (GPP), fever, systemic inflammation, and leukocytosis. We report the case of a 5-year-old girl with severe scalp and nail involvement with a rapid response to secukinumab.

Symmetrical peripheral gangrene following brain surgery.

Symmetric peripheral gangrene is a rare but devastating complication, scarcely reported after brain surgery. We present a case of symmetric peripheral gangrene shortly after brain surgery of intracranial hematoma removal and aneurysm clipping.

Platycodon grandiflorum extract attenuates lipopolysaccharide-induced acute lung injury via TLR4/NF-κBp65 pathway in rats.

The traditional Chinese medicine Platycodon grandiflorum (PG) is often used for the treatment of a number of chronic inflammatory diseases. In Chinese veterinary clinic, PG is always extracted by decoction and taken orally, however, the molecular mechanism of PG extract (PE) to reduce LPS-induced inflammation, especially acute lung injury (ALI) in vivo, are not known. Thus, we have studied the anti-inflammatory effects of PE on lipopolysaccharide (LPS)-induced acute lung injury via TLR4/NF-κBp65 pathway in rat. Sprague-Dawley rats were randomly divided into 4 groups: control group, LPS group, LPS±PE low dose group and LPS±PE high dose group. All rats were given corresponding PE solution or the same amount of normal saline by intragastric administration for 7 days. On the 7th day, 1 h after the last administration, 500 µg of LPS were introduced intratracheally to establish ALI rat model, and the same volume of normal saline was given to control group. The results showed that PE reduced the levels of LPS-induced pro-inflammatory mediators including IL-6, PGE2, and TNF-α, alleviated the lung injury histologically, and down-regulated LPS-induced mRNA and protein levels of TLR4/NF-κBp65 in lung tissue. This study demonstrated that PE has the anti-inflammatory effects on LPS-induced ALI in rats through TLR4/NF-κBp65 signaling pathway, indicating that PE is an effective suppressor for anti-inflammatory activities.

Tooth loss associated with the use of tenofovir disoproxil fumarate.

WHAT IS KNOWN AND OBJECTIVE: The frequent tenofovir disoproxil fumarate (TDF)-related adverse drug reactions (ADRs) are nephrotoxicity and bone toxicity; however, tooth-related ADRs of TDF have not been reported. We describe the case of a 41-year-old Han Chinese man with chronic hepatitis B with TDF-associated tooth loss. CASE SUMMARY: He presented with halitosis, gingival swelling and tooth loss after TDF use. After excluding the possibility of other drug-related ADRs, TDF was considered a possible cause and switched with tenofovir alafenamide fumarate (TAF). After 6 months, the oral symptoms disappeared, with no additional tooth loss. WHAT IS NEW AND CONCLUSION: This is the first report of such ADRs. The ADR score was 7, indicating tooth loss as a potential TDF-related ADR.

[Research and development of new traditional Chinese medicine drugs for certain syndromes based on "theoretical innovation"].

Compound prescription of traditional Chinese medicine(TCM), the main form in prevention and treatment of diseases in TCM, has unique advantages in medical practice. New TCM drugs for certain syndromes serve as an important carrier of inheritance and innovation in TCM. The research and development of new TCM drugs for certain syndromes should be based on the theory of TCM, guided by clinical value, and based on the principle of quality, safety and effectiveness. Through the innovative understanding of disease development rules, clinicians carry out academic theory innovation to guide clinical practice, aiming to effectively promote academic innovation and the development of new TCM drugs for certain syndromes. In this paper, we expounded some understanding of the innovation system of TCM, and analyzed the research value of new TCM drugs for certain syndromes. Based on theoretical innovation, the overall research model was preliminarily put forward. Subsequently, a concrete discussion from three aspects, including pharmaco-logy and toxicology, pharmacy and clinic research, was made on the specific process and existing problems of new drug research and development of TCM. Our research group attempts to establish a new drug innovation ecosystem for TCM syndrome, with the purpose of providing reference for other researchers.

[Research progress on effective components of Chinese materia medica in regulating autophagy].

Autophagy is a highly conservative and multi-component activated energy metabolism and self-renewal mechanism, which plays a crucial regulatory role in maintaining the normal physiological state of cells and is involved in various pathological processes. In recent years, the mechanism study has made great progress in regulating autophagy with effective components of Chinese materia medica(CMM),which are reported to prevent and treat cancers, neurodegenerative diseases, cardiovascular diseases and metabolic and immune-related diseases. This review outlines the molecular regulation mechanisms of cell autophagy with CMM components in controlling the above-mentioned diseases. There are many relevant reports on the regulatory mechanisms of autophagy in tumor and cardiovascular cells with CMM monomers. The main chemical structural types are alkaloids, saponins, polyphenols, flavonoids and terpenes. And m-TOR pathway is the main mechanism relating to the regulatory mechanisms of autophagy with CMM. Therefore, the regulatory mec-hanisms of cell autophagy become a new research targeting strategy of therapies with CMM. This review provides evidences for the effectiveness and scientificity of CMM in regulating autophagy, in the expectation of providing references for the in-depth studies of CMM in the field of autophagy and the development of natural autophagy regulators.

Long-term exposure of 4-hydroxyestradiol induces the cancer cell characteristics via upregulating CYP1B1 in MCF-10A cells.

Life-long estrogen exposure is one of the major risk factors in the development and progression of breast cancer. However, little is known about the molecular mechanisms, by which chronic exposure to estrogen contributes to breast carcinogenesis. The aim of the present study was to investigate the effects of long-term exposure with 4-hydroxyestradiol (4-OHE2) on acquired cancer characteristics of human mammary epithelial MCF-10A cells. The possible regulators were further studied in chronic 4-OHE2-treated MCF-10A cells. We observed that MCF-10A cells long-term exposed to 4-OHE2 acquire the characteristics of cancer cells, such as enhanced cell growth, EMT properties, and increased migration and invasiveness. Moreover, the expression of CYP1B1 was significantly elevated in long-term 4-OHE2-treated MCF-10A cells. Block of CYP1B1 significantly reduced the cancer cell characteristics in long-term 4-OHE2-treated MCF-10A cells. Our results indicated that 4-OHE2 mediated enhanced cancer cell characteristics in mammary epithelial cells are an important key event for breast carcinogenesis process. CYP1B1 partially contributes to the 4-OHE2 induced cancer cell characteristics in MCF-10A cells. Targeting CYP1B1 might offer a new strategy for the treatment of estrogen-induced breast cancer.

[Report of two cases of primary mediastinal tuberculosis].

Two cases of primary mediastinal lymphonode tuberculosis involved right bronchus were summarized in the report. Major clinical symptoms included cough and bloody sputum. Chest enhanced CT scan showed mediastinal lymph node enlargement with ring-shaped enhancement. Bronchoscopy suggested neoplasm in right bronchus. Diagnosis of tuberculosis was confirmed by histopathology in samples from lymph node puncture and brochoscopic biopsy. The clinical symptoms and medical imaging of patients were improved after transbrochoscopic interventional therapy and systemic chemotherapy.

Melatonin set out to ER stress signaling thwarts epithelial mesenchymal transition and peritoneal dissemination via calpain-mediated C/EBPß and NFκB cleavage.

Peritoneal dissemination of tumor has high mortality and is associated with the loss of epithelial features, acquisition of motile mesenchymal morphology characteristics, and invasive properties by tumor cells. Melatonin is an endogenously produced molecule in all plant species that is known to exert antitumor activity, but to date, its underlying mechanisms and antiperitoneal metastasis efficacy is not well defined. This study determined the antiperitoneal dissemination potential of melatonin in vivo and assessed its association with the inhibition of epithelial-to-mesenchymal transition (EMT) signaling mechanism by endoplasmic reticulum (ER) stress, which may be a major molecular mechanism of melatonin against cancer. The results demonstrate that melatonin inhibited peritoneal metastasis in vivo and activated ER stress in Cignal ERSE Reporter Assay, organelle structure in transmission electron microscopy images, calpain activity, and protein biomarkers like p-elf2α. Moreover, the overexpression of transcription factor C/EBPß in gastric cancer interacted with NFκB and further regulates COX-2 expression. These were dissociated and downregulated by melatonin, as proven by immunofluorescence imaging, immunoprecipitation, EMSA, and ChIP assay. Melatonin or gene silencing of C/EBPß decreased the EMT protein markers (E-cadherin, Snail, and Slug) and Wnt/beta-catenin activity by Topflash activity, and increased ER stress markers. In an animal study, the results of melatonin therapy were consistent with those of in vitro findings and attenuated systemic proangiogenesis factor production. In conclusion, C/EBPß and NFκB inhibition by melatonin may impede both gastric tumor growth and peritoneal dissemination by inducing ER stress and inhibiting EMT.

Haploidentical parental hematopoietic stem cell transplantation in pediatric refractory Langerhans cell histiocytosis.

Children with MS-LCH that fail to respond to conventional chemotherapy have poor outcomes. HSCT represents a potential salvage approach. It has been applied in over 50 cases in recent years. HSCT can achieve greater disease control than chemotherapy, but it carries a high risk of transplant-related mortality; thus, the haploidentical parental HSCT is used infrequently in pediatric refractory LCH. We report the first successful haploidentical parental HSCT, with no T-cell depletion, in two girls, aged 26 months and five months, with refractory MS-LCH. The mothers were donors with 5/6 and 4/6 HLA matches, respectively. The conditioning regimen included busulfan + cyclophosphamide + etoposide + antithymocyte-globulin ± fludarabine; the GVHD prophylaxis was based on cyclosporine + methotrexate ± mycophenolate-mofetil ± zenapax. In both cases, the stem cells were sourced from peripheral blood and BM, which included CD34+ cells (13.17 × 10(6)/kg and 40.23 × 10(6)/kg, respectively). These patients survived and showed no signs of disease activity in 54- and 44-month post-HSCT follow-ups. Our results indicated that, for patients that fail chemotherapy delivered early in the disease, but do not show organ dysfunction progression, it may be possible to achieve successful haploidentical parental HSCT with a strong myeloablative regimen.

A porcine early-onset scoliosis model created using a posterior mini-invasive method: a pilot study.

STUDY DESIGN: An animal study. OBJECTIVE: To create a reliable porcine scoliosis model representative of early-onset scoliosis (EOS) without violation of the vertebral elements along the curve. SUMMARY OF THE BACKGROUND DATA: To develop new nonfusion techniques for the treatment of EOS, a reliable large animal model with remarkable growth potential is required. However, a long tethering period which consumed the majority of the rapid growth phase or violation of the vertebral elements was thought to be essential in most of the previous models. Therefore, these models may be suboptimal for mimics of human EOS which was usually idiopathic type without vertebral anomalies. MATERIALS AND METHODS: This study included 12 female Yorkshire pigs (aged, 5-6 wk; weight, 5-7 kg) in which scoliosis was created by posterior asymmetric tethering from T5 to L3. At the index surgery, 3 separate incisions were preformed, and ipsilateral rib tethering from the 10th to the 13th rib was performed while maintaining the vertebral elements along the maximal curve in a pristine state. Progressive deformity was documented with monthly radiographs. Frontal and sagittal profiles were assessed using the Cobb method. After an 8-week tethering period, the whole instrumentations were removed, and the pigs were observed for an additional 8-week period with serial radiographs to document the progression of the deformity. RESULTS: Of the 12 pigs enrolled in this study, 2 encountered substantial complications (1 developed a postoperative infection, and the other experienced prolonged postoperative weakness). Of the 10 available for analysis, all pigs developed rapidly progressive, structurally 3-dimensional, idiopathic-type curves with convex to the right in the lower thoracic spine. The mean coronal Cobb angle was 29 degrees immediately postoperatively and progressed to 65 degrees after the 8-week tethering period. Eight weeks after removal of the tether, the scoliosis continued to progress and averaged 68 degrees (range, 58-78 degrees). On the sagittal plane, a mean lordosis of 32 degrees at the thoracic spine and a thoracolumbar kyphosis of 63 degrees were observed at study completion. CONCLUSIONS: A 3-dimensional rapidly progressive scoliosis model, that is closely approximate to human EOS, can be successfully created in pigs by unilaterally tethering the thoracolumbar spine and the ribcage. This model provides an equivalent EOS-like deformity and leaves adequate skeletal growth potential for biomechanical research as well as validation of fusionless scoliosis correction systems.

Quality of life in patients with breast cancer and their rehabilitation needs.

OBJECTIVE: We conducted a cross sectional study to investigate the quality of life (QOL) in breast cancer patients after treatment for one year and identify factors which may facilitate improvements in health care for breast cancer. METHODS: A total of 154 patients of breast cancer were collected from The First Affiliated Hospital of Harerbin Medical University during May 2008 and May 2010, and they were divided into three groups. The quality of life was assessed by Functional assessment of cancer therapy- breast (FACT-B) version 4, and a semi-structured interview was used to investigate the information and rehabilitation needs of the breast cancer patients. Results : Group II had the best social well-being, functional well-being and Total FACT-G among the three groups. Group III had the best physical well-being, emotional well-being, breast specific subscales, total FACT-B and TOI among the three groups. Higher PWB scores were significantly correlation with lower tumor stage; increased SWB scores were significantly correlated with education and occupation, and lower EWB scores were correlated with younger aged women and higher tumor stage (< 40 years). The semi-structured investigation showed all of them want to receive tumor markers detection and PET scan to prevent recurrence. 56% of these patients were worried about symptoms. 42% of the patients reported they had restriction in sexual relationship, and 57% wanted to improve their body image and reconstruction surgery. CONCLUSIONS: Breast cancer patients should be followed up for their quality of life and provided effective therapy for their physical and psychological problems.

An Automated Multi-scale Feature Fusion Network for Spine Fracture Segmentation Using Computed Tomography Images.

Spine fractures represent a critical health concern with far-reaching implications for patient care and clinical decision-making. Accurate segmentation of spine fractures from medical images is a crucial task due to its location, shape, type, and severity. Addressing these challenges often requires the use of advanced machine learning and deep learning techniques. In this research, a novel multi-scale feature fusion deep learning model is proposed for the automated spine fracture segmentation using Computed Tomography (CT) to these challenges. The proposed model consists of six modules; Feature Fusion Module (FFM), Squeeze and Excitation (SEM), Atrous Spatial Pyramid Pooling (ASPP), Residual Convolution Block Attention Module (RCBAM), Residual Border Refinement Attention Block (RBRAB), and Local Position Residual Attention Block (LPRAB). These modules are used to apply multi-scale feature fusion, spatial feature extraction, channel-wise feature improvement, segmentation border results border refinement, and positional focus on the region of interest. After that, a decoder network is used to predict the fractured spine. The experimental results show that the proposed approach achieves better accuracy results in solving the above challenges and also performs well compared to the existing segmentation methods.

Epidemiological Trends in Cardiovascular Disease Mortality Attributable to Modifiable Risk Factors and Its Association with Sociodemographic Transitions across BRICS-Plus Countries.

BRICS-Plus countries (Brazil, Russia, India, China, South Africa, and 30 other countries) is a group of 35 countries with emerging economies making up more than half of the world's population. We explored epidemiological trends of cardiovascular disease (CVD) mortality attributable to modifiable risk factors and its association with period and birth cohort effects and sociodemographic index (SDI) across BRICS-Plus countries by using joinpoint regression and age-period-cohort modeling from 1990 to 2019. Between 1990 and 2019, the all-ages CVD deaths increased by 85.2% (6.1 million to 11.3 million) across BRICS-Plus countries. The CVD age-standardized mortality rate attributable to dietary risks and smoking significantly decreased across BRICS-Plus countries, with some exceptions. However, four-fifths of BRICS-Plus countries observed a remarkable increasing trend of high body mass-index (BMI)-related CVD deaths, in particular, among younger adults (25-49 years). Early birth cohorts and individuals aged greater than 50 years showed a higher risk of CVD mortality. Both the China-ASEAN FTA and Mercosur regions stand out for their successful sociodemographic transition, with a significant reduction in CVD mortality over the study period. Singapore and Brazil achieved great progress in CVD mortality reduction and the other BRICS-Plus countries should follow their lead in adopting public health policies and initiatives into practice.

Potent growth-inhibitory effect of TRAIL therapy mediated by double-regulated oncolytic adenovirus on osteosarcoma.

Osteosarcoma (OS) severely threatens the health of young people and understanding on the molecular mechanisms of OS etiology enables gene therapy to become an effective therapeutic modality. However, insufficient expression level of genes using existing vectors limits the clinical application of gene therapy for OS. To solve the problem, we developed an oncolytic adenoviral vector, OAT, which can selectively and efficiently replicate in OS cells to enhance the expression of transferred genes. We demonstrated that OAT-mediated TRAIL expression is significantly elevated after infection of OS cells than replication-incompetent Ad5 vector. Increased antitumor capacity was observed in OS cells after OAT-TRAIL treatment both in vitro and in vivo. In normal cells, adenoviral replication, TRAIL expression and growth-inhibiting effect were quite limited when OAT-TRAIL was administrated, showing a high biosafety of this oncolytic adenoviral vector. Collectively, we generated an efficient and promising expression vector for OS gene therapy.