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Killing cancer cells through the induction of apoptosis is one of the main mechanisms of chemotherapy. However, numerous cancer cells have primary or acquired apoptosis resistance, resulting in chemoresistance. In this study, using a novel chalcone derivative chalcone-24 (Chal-24), we identified a novel anticancer mechanism through autophagy-mediated necroptosis (RIP1- and RIP3-dependent necrosis). Chal-24 potently killed different cancer cells with induction of necrotic cellular morphology while causing no detectable caspase activation. Blocking the necroptosis pathway with either necrostatin-1 or by knockdown of RIP1 and RIP3 effectively blocked the cytotoxicity of Chal-24, suggesting that Chal-24-induced cell death is associated with necroptosis. Chal-24 robustly activated JNK and ERK and blockage of which effectively suppressed Chal-24-induced cytotoxicity. In addition, Chal-24 strongly induced autophagy that is dependent on JNK-mediated phosphorylation of Bcl-2 and Bcl-xL and dissociation of Bcl-2 or Bcl-xL from Beclin-1. Importantly, suppression of autophagy, with either pharmacological inhibitors or small interfering RNAs targeting the essential autophagy components ATG7 and Beclin-1, effectively attenuated Chal-24-induced cell death. Furthermore, we found that autophagy activation resulted in c-IAP1 and c-IAP2 degradation and formation of the Ripoptosome that contributes to necroptosis. These results thus establish a novel mechanism for killing cancer cells that involves autophagy-mediated necroptosis, which may be employed for overcoming chemoresistance.

Purpose: At present, there is no gold standard or unified standard for the diagnosis of neurosyphilis, and the rate of misdiagnosis is high. The diagnosis of neurosyphilis is still challenging. This study compared the clinical indicators between neurosyphilis and latent syphilis infection in the central nervous system. The purpose of this study was to provide evidence for the differential diagnosis and prognosis of patients with neurosyphilis and latent syphilis infection of the central nervous system. Methods: The clinical data of 59 patients with neurosyphilis and 30 patients with latent syphilis infection in the nervous system from 2008 to 2021 were analyzed. The cerebrospinal fluid and serum biochemical markers were evaluated for all patients. Results: CSF-nucleated cells, CSF-TRUST, CSF-totalprotein and CSF-IgG (P<0.001) were significantly different between neurosyphilis and latent syphilis infection in the central nervous system. CSF-TRUST titer was positively correlated with D-D concentration (r = 0.274, P < 0.05), sodion (r =0.251, P < 0.05), respectively. Glucose concentration is the most unreliable in the diagnosis of neurosyphilis (AUC=0.445, P=0.395), and TRUST combined with nucleated cells and total protein is the most accurate in the diagnosis of neurosyphilis (AUC=0.989, P<0.001). Conclusion: The combination of TRUST, nucleated cell count and totalprotein detection in CSF can distinguish the patients with neurosyphilis and latent syphilis infection in the central nervous system, which has a significant diagnostic value. Keywords: neurosyphilis, latent syphilis infection, diagnosis, detection index

Diabetes mellitus (DM)-associated ED is predominantly due to neurovascular dysfunction mediated by nitric oxide (NO) suppression. Panax notoginseng saponins (PNS) are widely used for treating cardiovascular disease in China. The aim of this study was to evaluate the effects of PNS on penile erection and corpus cavernosum tissues in rats with diabetes-associated ED. Four weeks after PNS treatment, erectile function was assessed by intracavernous pressure (ICP) and mean arterial pressure (MAP) measurements. The level of NO, cyclic guanosine monophosphate (cGMP) and advanced glycation end products (AGEs) in cavernous tissue were assessed. Immunohistochemical staining and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) were performed for detecting endothelial NO synthase (eNOS) and apoptosis, respectively. The results show that ICP/MAP ratio was significantly increased in high-dose (150 mg kg −1 per day) PNS-treated group compared with the diabetic ED untreated group (DM group). Compared with the untreated group, the expression of eNOS and the levels of NO and cGMP were increased in the PNS-treated groups. Moreover, apoptosis was markedly decreased in the group that received 150 mg kg −1 per day of PNS. These results suggest that PNS may be used for improving the ED in diabetic rats via the NO/cGMP pathway and restores the function of endothelium in corpus cavernosum.

Prenatal depressive symptoms are an important mental health problem during pregnancy. We aimed to explore the moderating role of social support on the association between perceived stress and prenatal depressive symptoms. A cross-sectional study was conducted at an obstetrics clinic. A total of 1846 women completed a self-administered questionnaire, with a response rate of 91.8%. Of the 1846 participants, 28.2% reported prenatal depressive symptoms (Edinburgh postnatal depression scale score ≥ 9). After adjusting for demographic characteristics, gestational age, exercise, and passive smoking, both perceived stress (adjusted odds ratio (AOR): 1.210, 95% confidence interval (CI): 1.178-1.242) and social support (AOR: 0.950, 95% CI: 0.932-0.968) were associated with prenatal depressive symptoms. Moreover, social support had a moderating effect on the association between perceived stress and prenatal depressive symptoms ( < 0.001), and pregnant women with low social support were more likely to be affected by stress and experience prenatal depressive symptoms. Our study suggests that higher social support reduces the impact of stress on pregnant women, which in turn, decreases the risk of prenatal depressive symptoms. Therefore, interventions aimed at improving social support should be considered for the prevention and treatment of prenatal depressive symptoms.

The cracked chevron-notched Brazilian disc (CCNBD) was proposed by the International Society for Rock Mechanics (ISRM) to test the mode I (opening mode) fracture toughness of rock. The test method has been vigorously discussed and debated, despite being the subject of intensive research for decades. The minimum (critical) dimensionless stress intensity factors affiliated with the formula for calculating the fracture toughness using CCNBD specimens with different geometric parameters remain elusive and complex. The matter cannot be resolved by simply replacing the diameter in the original formula with the radius, as claimed by several authors. In this paper, the formula is fundamentally improved, as wide-ranging minimum dimensionless stress intensity factors pertaining to diversified CCNBD geometries are recalibrated by three-dimensional finite element analysis, and an expression with tabulated coefficients is obtained through curve-fitting the data obtained from the numerical calibration. The present results are shown to be more accurate than those in the literature. Furthermore, the importance of the reasonability of the results is highlighted; a comprehensive comparison of different values shows that the upper bounds of minimum stress intensity factors are violated by the above claim. The confusion resulting from the claim is, thus, clarified conclusively.

endocarditis (AE) is a highly fatal infection that can occur in heart valve replacement, pacemaker implantation and other heart surgeries, and early recognition and sufficient diagnosis are challenging. Here, we report the case of a 68-year-old male with a history of dilated cardiomyopathy and pacemaker implantation who had a repeated fever with failed antibacterial treatment and sterile blood culture. He developed endocarditis, and the culture and biopsy of vegetation tissue showed the abundant presence of septate hyphae, which was subsequently identified as by internal transcribed spacer (ITS) sequencing. Although the patient had serious side effects from voriconazole, he had a good prognosis following surgery and prolonged caspofungin antifungal therapy of 42 consecutive days. We discuss the diagnosis and treatment strategy of AE, and recommend galactomannan assays and next-generation sequencing for a timely diagnosis. Early surgical intervention combined with prompt antifungal therapy appears significant for survival.

Snail trails on photovoltaic modules are a source of enormous concern to the solar industry as few scientific reports on the mechanisms producing this global phenomenon were previously available. The samples surface were treated with CH3OH/CH2Cl2 and used the SEM and Raman for material analysis. The size of the discoloration silver grid is about 80-200 nm. From the Raman spectroscopy can be seen snail trails and the surrounding discoloration of silver on the Ag2CO3 generation.

Despite the importance of the Yellow River to China, climate change for the middle reaches of the Yellow River Basin (YRB) has been investigated far less than for other regions. This work focuses on future changes in mean and extreme climate of the YRB for the near-term (2021–2040), mid-term (2041–2060), and far-term (2081–2100) future, and assesses these with respect to the reference period (1986–2005) using the latest REgional MOdel (REMO) simulations, driven by three global climate models (GCMs) and assuming historical and future [Representative Concentration Pathway (RCP) 2.6 and 8.5] forcing scenarios, over the CORDEX East Asia domain at 0.22° horizontal resolution. The results show that REMO reproduces the historical mean climate state and selected extreme climate indices reasonably well, although some cold and wet biases exist. Increases in mean temperature are strongest for the far-term in winter, with an average increase of 5.6 °C under RCP 8.5. As expected, the future temperatures of the warmest day (TXx) and coldest night (TNn) increase and the number of frost days (FD) declines considerably. Changes to mean temperature and FD depend on elevation, which could be explained by the snow-albedo feedback. A substantial increase in precipitation (34%) occurs in winter under RCP 8.5 for the far-term. Interannual variability in precipitation is projected to increase, indicating a future climate with more extreme events compared to that of today. Future daily precipitation intensity and maximum 5-day precipitation would increase and the number of consecutive dry days would decline under RCP 8.5. The results highlight that pronounced warming at high altitudes and more intense rainfall could cause increased future flood risk in the YRB, if a high GHG emission pathway is realized.

Light redirecting ribbons (LRR) have recently been adopted in crystalline silicon modules in PV industry. The introduction of this LRR may bring additional stress at the boundary of the busbar/wafer contact, which may probably lead to higher power loss after aging. The thermal cycle and electroluminescence (EL) test are employed in this work to investigate this stress-induced power degradation for LRR-based crystalline silicon modules. The obtained results demonstrate that with increase in the thickness of the EVA encapsulant or the decrease in the thickness of the LRR, the power degradation induced by stress can be effectively diminished.

Summary Three cypress ( Juniperus przewalski Kom.) tree ring width chronologies were established based on tree ring cores collected at elevations ranging from 3,550–3,700 m a.s.l. in the headwaters of the Yellow River, Animaqin Mountains, in the northeastern Tibetan Plateau. Statistical analysis showed that the chronologies were negatively correlated to the summer half-year (April to September) maximum air temperature ( p < 0.01). The maximum temperature of the summer half-year was reconstructed for the past 700 years based on the developed chronologies. The reconstruction explains 47% of the maximum temperature variance which occurred during the period with meteorological observations (1959–2001). Both cold and warm periods were evident in the reconstructed summer half-year maximum temperature record over the past 700 years. The summer half-year maximum temperature has increased since the 1980s, and the decade 1980 to 1990 is ranked as one of the fastest warming decades on record, however this is not exceptional on centennial or millennial timescales. The ten-year average summer half-year maximum temperature in the 1990s is relatively high, but it is still colder than several other periods, including 1480s–1490s and 1590s–1600s. The 1480s is the warmest period in the past 700 years. The summer half-year maximum temperature can change significantly within decades. From 1490s to 1500s, the temperature dropped 0.89 °C. In the northeastern region of the Tibetan Plateau, warmer periods are often accompanied by drought whereas cold periods are coincident with above average precipitation.