miRNA profiling of granulosa cell-derived exosomes reveals their role in promoting follicle development.

To explore whether granulosa cell (GC)-derived exosomes (GC-Exos) and follicular fluid-derived exosomes (FF-Exos) have functional similarities in follicle development and to establish relevant experiments to validate whether GC-Exos could serve as a potential substitute for follicular fluid-derived exosomes to improve folliculogenesis. GC-Exos were characterized. MicroRNA (miRNA) profiles of exosomes from human GCs and follicular fluid were analyzed in depth. The signature was associated with folliculogenesis, such as phosphatidylinositol 3 kinases-protein kinase B signal pathway, mammalian target of rapamycin signal pathway, mitogen-activated protein kinase signal pathway, Wnt signal pathway, and cyclic adenosine monophosphate signal pathway. A total of five prominent miRNAs were found to regulate the above five signaling pathways. These miRNAs include miRNA-486-5p, miRNA-10b-5p, miRNA-100-5p, miRNA-99a-5p, and miRNA-21-5p. The exosomes from GCs and follicular fluid were investigated to explore the effect on folliculogenesis by injecting exosomes into older mice. The proportion of follicles at each stage is counted to help us understand folliculogenesis. Exosomes derived from GCs were isolated successfully. miRNA profiles demonstrated a remarkable overlap between the miRNA profiles of FF-Exos and GC-Exos. The shared miRNA signature exhibited a positive influence on follicle development and activation. Furthermore, exosomes derived from GCs and follicular fluid promoted folliculogenesis in older female mice. Exosomes derived from GCs had similar miRNA profiles and follicle-promoting functions as follicular fluid exosomes. Consequently, GC-Exos are promising for replacing FF-Exos and developing new commercial reagents to improve female fertility.

Quantitative regulation of electron-phonon coupling.

Electron-phonon (e-p) coupling plays a crucial role in various physical phenomena, and regulation of e-p coupling is vital for the exploration and design of high-performance materials. However, the current research on this topic lacks accurate quantification, hindering further understanding of the underlying physical processes and its applications. In this work, we demonstrate quantitative regulation of e-p coupling, by pressure engineering andin-situspectroscopy. We successfully observe both a distinct vibrational mode and a strong Stokes shift in layered CrBr3, which are clear signatures of e-p coupling. This allows us to achieve precise quantification of the Huang-Rhys factorSat the actual sample temperature, thus accurately determining the e-p coupling strength. We further reveal that pressure efficiently regulates the e-p coupling in CrBr3, evidenced by a remarkable 40% increase inSvalue. Our results offer an approach for quantifying and modulating e-p coupling, which can be leveraged for exploring and designing functional materials with targeted e-p coupling strengths.

Strong In-Plane Optoelectronic Anisotropy and Polarization Sensitivity in Low-Symmetry 2D Violet Phosphorus.

Anisotropic optoelectronics based on low-symmetry two-dimensional (2D) materials hold immense potential for enabling multidimensional visual perception with improved miniaturization and integration capabilities, which has attracted extensive interest in optical communication, high-gain photoswitching circuits, and polarization imaging fields. However, the reported in-plane anisotropic photocurrent and polarized dichroic ratios are limited, hindering the achievement of high-performance anisotropic optoelectronics. In this study, we introduce novel low-symmetry violet phosphorus (VP) with a unique tubular cross-linked structure into this realm, and the corresponding anisotropic optical and optoelectronic properties are investigated both experimentally and theoretically for the first time. Remarkably, our prepared VP-based van der Waals phototransistor exhibits significant optoelectronic anisotropies with a giant in-plane anisotropic photocurrent ratio exceeding 10 and a comparable polarized dichroic ratio of 2.16, which is superior to those of most reported 2D counterparts. Our findings establish VP as an exceptional candidate for anisotropic optoelectronics, paving the way for future multifunctional applications.

OPA1, a molecular regulator of dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a disease with no specific treatment, poor prognosis and high mortality. During DCM development, there is apoptosis, mitochondrial dynamics imbalance and changes in cristae structure. Optic atrophy 1 (OPA1) appears at high frequency in these three aspects. DCM LMNA (LaminA/C) gene mutation can activate TP53, and the study of P53 shows that P53 affects OPA1 through Bak/Bax and OMA1 (a metalloprotease). OPA1 can be considered the missing link between DCMp53 and DCM apoptosis, mitochondrial dynamics imbalance and changes in cristae structure. OPA1 regulates apoptosis by regulating the release of cytochrome c from the mitochondrial matrix through CJs (crisp linkages, located in the inner mitochondrial membrane) and unbalances mitochondrial fusion and fission by affecting mitochondrial inner membrane (IM) fusion. OPA1 is also associated with the formation and maintenance of mitochondrial cristae. OPA1 is not the root cause of DCM, but it is an essential mediator in P53 mediating the occurrence and development of DCM, so OPA1 also becomes a molecular regulator of DCM. This review discusses the implication of OPA1 for DCM from three aspects: apoptosis, mitochondrial dynamics and ridge structure.

Association of triglyceride glucose index with all-cause and cardiovascular mortality in the general population.

OBJECTIVE: The Triglyceride-glucose (TyG) index, a novel indicator of insulin resistance, has been associated with mortality from coronary artery diseases, ischemic stroke, and heart failure. In recent years, much emphasis has been placed on the relationship between the TyG index and mortality in the general population. However, the impact of age on the association between TyG and all-cause and cardiovascular mortality remains controversial. This study investigated the link between the TyG index and all-cause and cardiovascular mortality, emphasizing differences between older and non-older populations. METHODS: Data from the National Health and Nutrition Examination Survey (2009-2018), encompassing 20,194 participants, were analyzed. The baseline TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Multivariate Cox proportional hazards regression models with restricted cubic splines and trend tests were employed to explore the association between the TyG index and all-cause and cardiovascular mortality, with emphasis on age-specific analysis. Subgroup analysis was conducted to examine whether the TyG index's association with mortality varied across different subgroups. Additionally, receiver operating characteristic curves were used to compare the predictive ability of the TyG index with the homeostasis model assessment of insulin resistance (HOMA-IR) for all-cause and cardiovascular mortality. RESULTS: Over a median follow-up period of 105 months, all-cause mortality accounted for 13.345% of cases, and cardiovascular mortality accounted for 3.387%. Kaplan-Meier curves showed a significant increase in all-cause and cardiovascular mortality with higher TyG index values (both P for log-rank test < 0.001). However, during Cox proportional hazards regression analysis, no linear trend was observed between the TyG index and all-cause or cardiovascular mortality after adjusting for confounding factors (all-cause mortality: P for trend = 0.424; cardiovascular mortality: P for trend = 0.481). Restricted cubic splines revealed a non-linear association between the baseline TyG index and all-cause and cardiovascular mortality in the overall population (all-cause mortality: Non-linear P = 0.003; cardiovascular mortality: Non-linear P = 0.034). The effect of the TyG index was consistent across most subgroups in terms of all-cause and cardiovascular mortality, with no significant interaction with randomized factors (all-cause mortality: P for interaction = 0.077-0.940, cardiovascular mortality: P for interaction = 0.173-0.987), except for the age subgroup (all-cause mortality: P for interaction < 0.001, cardiovascular mortality: P for interaction < 0.001). Further age-specific analysis revealed that the association between the TyG index and all-cause and cardiovascular mortality remained significant in patients aged < 65 but not in those aged ≥ 65. Interestingly, a non-linear association was observed between the TyG index and all-cause mortality in individuals aged < 65 (Non-linear P = 0.011), while a linear relationship was observed with cardiovascular mortality, showing an upward trend (Non-linear P = 0.742, P for trend = 0.010). Further stratification according to age yielded similar results only in patients aged 45-64 (all-cause mortality: Non-linear P = 0.001 and cardiovascular mortality: Non-linear P = 0.902, P for trend = 0.015). Compared to HOMA-IR, the TyG index demonstrated superior predictive performance for all-cause and cardiovascular mortality (all-cause mortality: 0.620 vs. 0.524, P < 0.001; cardiovascular mortality: 0.623 vs. 0.537, P < 0.001). CONCLUSIONS: This study established a significant association between the TyG index and all-cause and cardiovascular mortality in the general population, particularly among individuals aged < 65. Notably, a non-linear association with all-cause mortality was observed in those aged < 65, while a linear relationship with cardiovascular mortality was found.

Association between monocyte to high-density lipoprotein cholesterol ratio and multi-vessel coronary artery disease: a cross-sectional study.

BACKGROUND: Patients with multi-vessel coronary artery disease (MV-CAD) have poorer clinical outcomes than those with single-vessel coronary artery disease (SV-CAD). Solid evidence underlines that high-density lipoprotein cholesterol (HDL-C) plays a protective role and monocyte plays a negative role in coronary artery disease (CAD). However, the monocyte to high-density lipoprotein ratio (MHR) has not been studied in relation to MV-CAD. METHODS: In this study, 640 patients underwent coronary angiography, of whom 225 had severe coronary artery disease. Then divide the above two groups of patients into three groups based on the MHR tertiles, respectively. Logistic regression and subgroup analysis were carried out to estimate the association between MHR and MV-CAD. The receiver operating characteristic (ROC) curve analysis was constructed by combining classic CAD risk factors with MHR in response to MV-CAD. In addition, the mediating effect of MHR between smoking and MV-CAD in suspected CAD Patients was analyzed. RESULTS: Among the three MHR groups, a statistically discrepant was observed in the number of patients with CAD, Severe-CAD and MV-CAD (PCAD < 0.001; PSevere-CAD < 0.001; PMV-CAD = 0.001) in suspected CAD patients. Furthermore, the number of patients with MV-CAD (P < 0.001) was different in Severe-CAD patients among three MHR groups. Non-CAD and CAD patients showed statistically discrepant in MHR levels (P < 0.001), and this difference also was observed between SV-CAD and MV-CAD patients (P < 0.001). In the analysis of suspected CAD patients, a significantly positive relationship was found between MHR and CAD, Severe-CAD, and MV-CAD (P for trend < 0.001). The effect of MHR on MV-CAD was consistent across all subgroups, with no significant randomized factor-by-subgroup interaction (P-interaction = 0.17-0.89). ROC analysis showed that the model constructed with MHR and classic influencing factors of CAD was superior to the model constructed solely based on classic influencing factors of CAD (0.742 vs.0.682, P = 0.002). In the analysis of Severe-CAD patients, patients with higher MHR levels had a higher risk of MV-CAD [OR (95%CI): 2.90 (1.49, 5.62), P for trend = 0.002] compared to patients with lower MHR. The trends persisted after adjusting for demographic (P for trend = 0.004) and classic influencing factors of CAD (P for trend = 0.009). All subgroup factors for patients with MV-CAD had no interaction with MHR (P-interaction = 0.15-0.86). ROC analysis showed that the model combining MHR and classic influencing factors of CAD was superior to the one including only the classic influencing factors of CAD (0.716 vs.0.650, P = 0.046). Assuming that MHR played a mediating effect between smoking and MV-CAD in suspected CAD patients. The results indicated that MHR played a partial mediating effect of 0.48 (P < 0.001). CONCLUSION: A higher MHR was mainly associated with multi-vessel coronary artery disease and MHR partially mediated the association between smoking and MV-CAD.

Strain Tunability of Perpendicular Magnetic Anisotropy in van der Waals Ferromagnets VI3.

Layered ferromagnets with strong magnetic anisotropy energy (MAE) have special applications in nanoscale memory elements in electronic circuits. Here, we report a strain tunability of perpendicular magnetic anisotropy in van der Waals (vdW) ferromagnets VI3 using magnetic circular dichroism measurements. For an unstrained flake, the M-H curve shows a rectangular-shaped hysteresis loop with a large coercivity (1.775 T at 10 K) and remanent magnetization. Furthermore, the coercivity can be enhanced to a maximum of 2.6 T under a 3.8% external in-plane tensile strain. Our DFT calculations show that the increased MAE under strain contributes to the enhancement of coercivity. Meanwhile, the strain tunability on the coercivity of CrI3, with a similar crystal structure, is limited. The main reason is the strong spin-orbit coupling in V3+ in VI6 octahedra in comparison with that in Cr3+. The strain tunability of coercivity in VI3 flakes highlights its potential for integration into vdW heterostructures.

Observation of Ultrastrong Coupling between Substrate and the Magnetic Topological Insulator MnBi2Te4.

The intrinsic magnetic topological insulator MnBi2Te4 has attracted significant interest recently as a promising platform for exploring exotic quantum phenomena. Here we report that, when atomically thin MnBi2Te4 is deposited on a substrate such as silicon oxide or gold, there is a very strong mechanical coupling between the atomic layer and the supporting substrate. This is manifested as an intense low-frequency breathing Raman mode that is present even for monolayer MnBi2Te4. Interestingly, this coupling turns out to be stronger than the interlayer coupling between the MnBi2Te4 atomic layers. We further found that these low-energy breathing modes are highly sensitive to sample degradation, and they become drastically weaker upon ambient air exposure. This is in contrast to the higher energy optical phonon modes which are much more robust, suggesting that the low-energy Raman modes found here can be an effective indicator of sample quality.

Multiplication-free timing phase error detector for Nyquist and non-Nyquist optical signals.

A versatile digital coherent receiver capable of handling optical signals with different kinds of pulse shaping schemes (PSSs) is indispensable for future flexible and heterogeneous coherent optical communication networks. Therefore, a low-complexity timing phase error detector (TPED) versatile for all PSSs is of particular interest. In this paper, we propose a TPED suitable for both Nyquist signals with different roll-off factors and non-Nyquist signals. It requires two samples per symbol and involves no multiplications. As far as we know, it has the lowest computation complexity compared with the existing TPEDs used in coherent systems, while incurring no receiver sensitivity penalty. Numerical simulations and experiments are carried out to demonstrate the superior timing performance and PSS versatility of the proposed TPED in both open-loop and closed-loop working conditions. We also implement the novel TPED in a field programmable gate array (FPGA) and verify its real-time clock recovery performance using the 10 Gbaud very low roll-off Nyquist and non-Nyquist quadrature phase shift keying (QPSK) signals.

Nodal and Nematic Superconducting Phases in NbSe_{2} Monolayers from Competing Superconducting Channels.

Transition metal dichalcogenides like 2H-NbSe_{2} in their two-dimensional (2D) form exhibit Ising superconductivity with the quasiparticle spins being firmly pinned in the direction perpendicular to the basal plane. This enables them to withstand exceptionally high magnetic fields beyond the Pauli limit for superconductivity. Using field-angle-resolved magnetoresistance experiments for fields rotated in the basal plane we investigate the field-angle dependence of the upper critical field (H_{c2}), which directly reflects the symmetry of the superconducting order parameter. We observe a sixfold nodal symmetry superposed on a twofold symmetry. This agrees with theoretical predictions of a nodal topological superconducting phase near H_{c2}, together with a nematic superconducting state. We demonstrate that in NbSe_{2} such unconventional superconducting states can arise from the presence of several competing superconducting channels.

EGCG protects cardiomyocytes against hypoxia-reperfusion injury through inhibition of OMA1 activation.

Mitochondria are important for energy production and cardiomyocyte homeostasis. OMA1, a metalloendopeptidase, initiates the proteolytic process of the fusion-allowing protein OPA1, to deteriorate mitochondrial structure and function. In this study, mouse embryonic fibroblasts (MEFs) and neonatal mouse cardiomyocytes (NMCMs) subjected to hypoxia-reperfusion injury (HRI) and/or H2O2 were used to mimic oxidative stress in the heart following ischemia-reperfusion injury (IRI). In vitro experiments demonstrated that HRI or stimulation with H2O2 induced self-cleavage of OMA1 and the subsequent conversion of OPA1 from its long form to its short form, leading to mitochondrial fragmentation, cytochrome c release and apoptosis. By using Molecular Operating Environment (MOE) software to simulate the binding interaction of 2295 phytochemicals against OMA1, epigallocatechin gallate (EGCG) and betanin were selected as candidates of OMA1 inhibitor. We found that EGCG directly interacted with OMA1 and potently inhibited self-cleavage of OMA1, leading to attenuated OPA1 cleavage. This study, therefore, suggests to use OMA1 inhibition induced by EGCG to treat cardiac IRI.

Ectodysplasin A receptor (EDAR) promotes colorectal cancer cell proliferation via regulation of the Wnt/ß-catenin signaling pathway.

Colorectal cancer is the second leading cause of cancer mortality worldwide with poor prognosis and high recurrence. Aberrant Wnt/ß-catenin signaling promotes oncogenesis by transcriptional activation of c-Myc and its downstream signals. EDAR is characterized as an important effector of canonical Wnt signaling in developing skin appendages, but the interplay between EDAR and Wnt signaling in tumorigenesis and progression remains to be elucidated. In this study, we revealed that EDAR expression is prevalently elevated in colorectal cancer tissues compared with normal tissues. Further analysis suggests there is a strict correlation between EDAR expression and colorectal cancer progression. EDAR silencing by shRNA in colorectal cancer cells showed proliferative suppression via retarding cell cycle at G1 phase. Xenograft mice transplanted with shEDAR-transduced tumor cells significantly alleviated tumor burden in comparison with control mice. Furthermore, downregulation of EDAR was accompanied by reduction of ß-catenin, c-Myc and other G1 cell cycle regulators, while ß-catenin agonist restored the expression of these proteins and overrode the proliferative block induced by EDAR knockdown. These findings indicate that EDAR functions as a component of Wnt/ß-catenin signaling pathway, and is a potential modulator in colorectal carcinogenesis.

Probing the Ferromagnetism and Spin Wave Gap in VI3 by Helicity-Resolved Raman Spectroscopy.

Circularly polarized light carries light spin angular momentum, which may lead helicity-resolved Raman scattering to be sensitive to the electronic spin configuration in magnetic materials. Here, we demonstrate that all Raman modes in the 2D ferromagnet VI3 show different scattering intensities to left and right circularly polarized light at low temperatures, which gives direct evidence of the time-reversal symmetry breaking. By measuring the circular polarization of the dominant Raman mode with respect to the temperature and magnetic field, the ferromagnetic (FM) phase transition and hysteresis behavior can be clearly resolved. Besides the lattice excitations, quasielastic scattering is detected in the paramagnetic phase, and it gradually evolves into the acoustic magnon mode at 18.5 cm-1 in the FM state, which gives the spin wave gap that results from large magnetic anisotropy. Our findings demonstrate that helicity-resolved Raman spectroscopy is an effective tool to directly probe the ferromagnetism in 2D magnets.

Magnetic Order-Induced Polarization Anomaly of Raman Scattering in 2D Magnet CrI3.

The recent discovery of 2D magnets has revealed various intriguing phenomena due to the coupling between spin and other degrees of freedoms (such as helical photoluminescence, nonreciprocal SHG). Previous research on the spin-phonon coupling effect mainly focuses on the renormalization of phonon frequency. Here we demonstrate that the Raman polarization selection rules of optical phonons can be greatly modified by the magnetic ordering in 2D magnet CrI3. For monolayer samples, the dominant A1g peak shows an abnormally high intensity in the cross-polarization channel at low temperatures, which is forbidden by the selection rule based on the lattice symmetry. For the bilayer, this peak is absent in the cross-polarization channel for the layered antiferromagnetic (AFM) state and reappears when it is tuned to the ferromagnetic (FM) state by an external magnetic field. Our findings shed light on exploring the emergent magneto-optical effects in 2D magnets.

Catechin relieves hypoxia/reoxygenation-induced myocardial cell apoptosis via down-regulating lncRNA MIAT.

BACKGROUND: Catechin protects heart from myocardial ischaemia/reperfusion (MI/R) injury. However, whether catechin inhibits H/R-induced myocardial cell apoptosis is largely unknown. OBJECTIVE: This study aims to investigate the underlying mechanism of catechin in inhibiting the apoptosis of H/R-induced myocardial cells. METHODS: LncRNA MIAT expression was detected by qRT-PCR. Cell viability of H9C2 cells was detected using CCK-8 assay. The apoptosis of H9C2 cells was detected by flow cytometry. The interaction between CREB and MIAT promoter regions was confirmed by dual-luciferase reporter gene assay and ChIP assay. RESULTS: In MI/R rats, catechin improved heart function and down-regulated lncRNA MIAT expression in myocardial tissue. In H/R-induced H9C2 cells, catechin protected against cell apoptosis, and lncRNA MIAT overexpression attenuated this protective effect of catechin. We confirmed that transcription factor CREB could bind to MIAT promoter region, and catechin suppressed lncRNA MIAT expression through up-regulating CREB. Catechin improved mitochondrial function and relieved apoptosis through promoting Akt/Gsk-3ß activation. In addition, MIAT inhibited Akt/Gsk-3ß activation and promoted cell apoptosis in H/R-induced H9C2 cells. Finally, we found catechin promoted Akt/Gsk-3ß activation through inhibiting MIAT expression in H/R-induced H9C2 cells. CONCLUSION: Catechin relieved H/R-induced myocardial cell apoptosis through regulating CREB/lncRNA MIAT/Akt/Gsk-3ß pathway.

From Anomalous to Normal: Temperature Dependence of the Band Gap in Two-Dimensional Black Phosphorus.

The temperature dependence of the band gap is crucial to a semiconductor. Bulk black phosphorus is known to exhibit an anomalous behavior. Through optical spectroscopy, here we show that the temperature effect on black phosphorus band gap gradually evolves with decreasing layer number, eventually turns into a normal one in the monolayer limit, rendering a crossover from the anomalous to the normal. Meanwhile, the temperature-induced shift in optical resonance also differs with different transition indices for the same thickness sample. A comprehensive analysis reveals that the temperature-tunable interlayer coupling is responsible for the observed diverse scenario. Our study provides a key to the apprehension of the anomalous temperature behavior in certain layered semiconductors.

Predicting Severe Enterovirus 71-Infected Hand, Foot, and Mouth Disease: Cytokines and Chemokines.

Enterovirus 71 (EV71) is one of the most common intestinal virus that causes hand, foot, and mouth disease (HFMD) in infants and young children (mostly ≤5 years of age). Generally, children with EV71-infected HFMD have mild symptoms that resolve spontaneously within 7-14 days without complications. However, some EV71-infected HFMD cases lead to severe complications such as aseptic meningitis, encephalitis, acute flaccid paralysis, pulmonary edema, cardiorespiratory complication, circulatory disorders, poliomyelitis-like paralysis, myocarditis, meningoencephalitis, neonatal sepsis, and even death. The mechanism of EV71 pathogenesis has been studied extensively, and the regulation of host immune responses is suspected to aggravate EV71-induced severe complications. Recently, several cytokines or chemokines such as TNF-α, IFN-γ, IL-1ß, IL-18, IL-33, IL-37, IL-4, IL-13, IL-6, IL-12, IL-23, IL-27, IL-35, IL-10, IL-22, IL-17F, IL-8, IP-10, MCP-1, G-CSF, and HMGB1 have been reported to be associated with severe EV71 infection by numerous research teams, including our own. This review is aimed at summarizing the pathophysiology of the cytokines and chemokines with severe EV71 infection.

Upregulation of miR-196b-5p attenuates BCG uptake via targeting SOCS3 and activating STAT3 in macrophages from patients with long-term cigarette smoking-related active pulmonary tuberculosis.

BACKGROUND: Cigarette smoking (CS) triggers an intense and harmful inflammatory response in lungs mediated by alveolar and blood macrophages, monocytes, and neutrophils and is closely associated with prevalence of tuberculosis (TB). The risk of death in patients with long-term cigarette smoking-related pulmonary tuberculosis (LCS-PTB) is approximately 4.5 times higher than those with nonsmoking pulmonary tuberculosis (N-PTB). However, the mechanisms underlying the harmful inflammatory responses in the setting of LCS-PTB have not been well documented. METHODS: 28 cases LCS-PTB patients, 22 cases N-PTB patients and 20 cases healthy volunteers were enrolled in this study. Monocytes were isolated from peripheral blood mononuclear cells. Differentiated human MDM and U937 cell were prepared with M-CSF and PMA stimulation, respectively. The miR-196b-5p, STAT1, STAT3, STAT4, STAT5A, STAT5B, STAT6, SOCS1 and SOCS3 mRNA expression were detected by qRT-PCR. Western blot was performed according to SOCS1, SOCS3, and pSTAT3 expression. The mycobacterial uptake by MDMs from different groups of patients after Bacillus Calmette-Guérin (BCG) infection and agomir-196b-5p or antagomir-196b-5p transfection were used by flow cytometry analysis. Human IL-6, IL-10 and TNF-α levels on the plasma and cell culture supernatant samples were measured using ELISA. For dual-luciferase reporter assay, the SOCS3 3'-UTR segments, containing the binding elements of miR-196b-5p or its mutant versions were synthesized as sense and antisense linkers. RESULTS: In this study, we found that IL-6, TNF-α production, SOCS3 mRNA expression were downregulated, while miR-196b-5p and STAT3 mRNA expression were upregulated in monocytes from LCS-PTB patients as compared to N-PTB patients. Meanwhile, we demonstrated that miR-196b-5p could target SOCS3 and activate STAT3 signaling pathway, which may possibly contribute to attenuation of BCG uptake and decrease in IL-6 and TNF-α production in macrophages. CONCLUSIONS: Our findings revealed that CS exposure regulates inflammatory responses in monocyte/macrophages from LCS-PTB patients via upregulating miR-196b-5p, and further understanding of the specific role of miR-196b-5p in inflammatory responses mightfacilitate elucidating the pathogenesis of LCS-PTB, thus leading to the development of new therapeutic strategies for PTB patients with long-term cigarette smoking.

Intelligent system to predict intradialytic hypotension in chronic hemodialysis.

BACKGROUND: Intradialytic hypotension (IDH) is a serious complication and a major risk factor of increased mortality during hemodialysis (HD). However, predicting the occurrence of intradialytic blood pressure (BP) fluctuations clinically is difficult. This study aimed to develop an intelligent system with capability of predicting IDH. METHODS: In developing and training the prediction models in the intelligent system, we used a database of 653 HD outpatients who underwent 55,516 HD treatment sessions, resulting in 285,705 valid BP records. We built models to predict IDH at the next BP check by applying time-dependent logistic regression analyses. RESULTS: Our results showed the sensitivity of 86% and specificity of 81% for both nadir systolic BP (SBP) of <90 mmHg and <100 mmHg, suggesting good performance of our prediction models. We obtained similar results in validating via test data and data of newly enrolled patients (new-patient data), which is important for simulating prospective situations wherein dialysis staff are unfamiliar with new patients. This compensates for the retrospective nature of the BP records used in our study. CONCLUSION: The use of this validated intelligent system can identify patients who are at risk of IDH in advance, which may facilitate well-timed personalized management and intervention.

An injured man with acute altered mental status.

CLINICAL INTRODUCTION: A 58-year-old man sustained injuries due to accidental fall from a height of 5 m onto a solid floor while operating a crane. He was fully conscious without external evidence of head injury when presented to the ED. The patient had multiple fractures involving the fourth, fifth and seventh of the left ribs, left iliac wing and superior ramus of the pelvis, comminuted fracture of the left femur shaft, and an open fracture of the mandible. Two hours after ED presentation, the patient developed acute confusion and lethargy, which rapidly progressed to coma and respiratory distress, and was subsequently intubated with mechanical ventilation support. Emergent CT scan of the head is shown (figure 1).emermed;35/3/148/F1F1F1Figure 1CT scan of the head without contrast. QUESTION: What is the most likely diagnosis?A. Cerebral haemorrhageB. Brain metastasisC. Cerebral fat embolismD. Diffuse axonal injury.