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Abstract Background Cognitive impairment is a recognized fundamental deficit in individuals diagnosed with schizophrenia (SZ), bipolar II disorder (BD II), and major depressive disorder (MDD), among other psychiatric disorders. However, limited research has compared cognitive function among first-episode drug-naïve individuals with SZ, BD II, or MDD. Methods This study aimed to address this gap by assessing the cognitive performance of 235 participants (40 healthy controls, 58 SZ patients, 72 BD II patients, and 65 MDD patients) using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) before and after 12 weeks of treatment in SZ, BD II, and MDD patients. To clarify, the healthy controls only underwent RBANS testing at baseline, whereas the patient groups were assessed before and after treatment. The severity of symptoms in SZ patients was measured using the Positive and Negative Syndrome Scale (PANSS), and depression in BD II and MDD patients was assessed using the Hamilton Depression Scale-24 items (HAMD-24 items). Results Two hundred participants completed the 12-week treatment period, with 35 participants dropping out due to various reasons. This group included 49 SZ patients, 58 BD II patients, and 53 MDD patients. Among SZ patients, significant improvements in immediate and delayed memory were observed after 12 weeks of treatment compared to their initial scores. Similarly, BD II patients showed significant improvement in immediate and delayed memory following treatment. However, there were no significant differences in RBANS scores for MDD patients after 12 weeks of treatment. Conclusions In conclusion, the findings of this study suggest that individuals with BD II and SZ may share similar deficits in cognitive domains. It is important to note that standardized clinical treatment may have varying degrees of effectiveness in improving cognitive function in patients with BD II and SZ, which could potentially alleviate cognitive dysfunction.

Abstract Background Distinguishing untreated major depressive disorder without medication (MDD) from schizophrenia with depressed mood (SZDM) poses a clinical challenge. This study aims to investigate differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognition in untreated MDD and SZDM patients. Methods The study included 42 untreated MDD cases, 30 SZDM patients, and 46 healthy controls (HC). Cognitive assessment utilized the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Resting-state functional magnetic resonance imaging (rs-fMRI) scans were conducted, and data were processed using fALFF in slow-4 and slow-5 bands. Results Significant fALFF changes were observed in four brain regions across MDD, SZDM, and HC groups for both slow-4 and slow-5 fALFF. Compared to SZDM, the MDD group showed increased slow-5 fALFF in the right gyrus rectus (RGR). Relative to HC, SZDM exhibited decreased slow-5 fALFF in the left gyrus rectus (LGR) and increased slow-5 fALFF in the right putamen. Changes in slow-5 fALFF in both RGR and LGR were negatively correlated with RBANS scores. No significant correlations were found between remaining fALFF (slow-4 and slow-5 bands) and RBANS scores in MDD or SZDM groups. Conclusions Alterations in slow-5 fALFF in RGR may serve as potential biomarkers for distinguishing MDD from SZDM, providing preliminary insights into the neural mechanisms of cognitive function in schizophrenia.

The gastrointestinal tract (GIT) is an important and complex system by which humans to digest food and absorb nutrients. The GIT is vulnerable to diseases, which may led to discomfort or even death in humans. Therapeutics for GIT disease treatment face multiple biological barriers, which significantly decrease the efficacy of therapeutics. Recognizing the biological barriers and pathophysiological characteristics of GIT may be helpful to design innovative therapeutics. Nanotherapeutics, which have special targeting and controlled therapeutic release profiles, have been widely used for the treatment of GIT diseases. Herein, we provide a comprehensive review of the biological barrier and pathophysiological characteristics of GIT, which may aid in the design of promising nanotherapeutics for GIT disease treatment. Furthermore, several typical diseases of the upper and lower digestive tracts, such as Helicobacter pylori infection and inflammatory bowel disease, were selected to investigate the application of nanotherapeutics for GIT disease treatment.

Abstract The heart primarily derives its energy through lipid oxidation. In cardiomyocytes, lipids are stored in lipid droplets (LDs) and are utilized in mitochondria, although the structural and functional connections between these two organelles remain largely unknown. In this study, visible evidence have presented indicating that a complex is formed at the mitochondria‐LD membrane contact (MLC) site, involving mitochondrion‐localized Mfn2 and LD‐localized Hsc70. This complex serves to tether mitochondria to LDs, facilitating the transfer of fatty acids (FAs) from LDs to mitochondria for β‐oxidation. Reduction of Mfn2 induced by lipid overload inhibits MLC, hinders FA transfer, and results in lipid accumulation. Restoring Mfn2 reinstates MLC, alleviating myocardial lipotoxicity under lipid overload conditions both in‐vivo and in‐vitro. Additionally, prolonged lipid overload induces Mfn2 degradation through the ubiquitin‐proteasome pathway, following Mfn2 acetylation at the K243 site. This leads to the transition from adaptive lipid utilization to maladaptive lipotoxicity. The experimental findings are supported by clinical data from patients with obesity and age‐matched non‐obese individuals. These translational results make a significant contribution to the molecular understanding of MLC in the heart, and offer new insights into its role in myocardial lipotoxicity.

Atmospheric turbulence causes transmitted light to fade randomly, which results in irradiance scintillation fluctuations in the received signal and significantly affects the quality of wireless optical communication systems. In this paper, we investigate the propagation characteristics of a monochromatic light-emitting diode (LED) light beam through weak-to-strong turbulence. Considering the spatial incoherence of a monochromatic LED light source, the emitted light field of a monochromatic LED light source is represented by a random field multiplied by a deterministic field that follows a Gaussian distribution. Then, based on the extended-Rytov theory, a closed expression for the irradiance scintillation index under weak-to-strong turbulence is derived. In addition, the expression for the fading probability governed by the Gamma–Gamma model is given. Finally, the effects of near-earth atmospheric refractive index structural parameters, signal propagation distances, and working light wavelengths on propagation characteristics of the LED-based VLC system are simulated and compared with those of the laser-based one. The results theoretically confirm that laser light sources are more susceptible to atmospheric turbulence along the propagation path than monochromatic LED light sources. The investigation in this paper can provide theoretical support for the design of visible light communication systems in practical applications.

Abstract Background At present, there is not enough evidence to prove the relationship between blood lipid and electrocardiogram (ECG) abnormalities in common mental disorders (CMD). This study aimed to explore the relationship between them, to detect and prevent arrhythmia or sudden death. Methods We collected 272 CMD patients (maintained a fixed drug dose pattern for 1 year or more), including 95 schizophrenias (SC), 90 bipolar disorders (BD) and 87 major depressive disorders (MDD), and 78 healthy controls (HC) from the Third People’s Hospital of Foshan, China. We analyzed and compared their blood lipid and ECG indicators, to clarify the relationship between them. Results 350 participants were included. There were no significant differences in age, gender, total cholesterol (TC), low density lipoprotein (LDL) and QTc (p > 0.05) among subjects. And there were significant differences in body mass index (BMI), triglyceride (TG), high density lipoprotein (HDL), heart rate, PR interval and QRS width (p

In the task of upper-limb pattern recognition, effective feature extraction, channel selection, and classification methods are crucial for the construction of an efficient surface electromyography (sEMG) signal classification framework. However, existing deep learning models often face limitations due to improper channel selection methods and overly specific designs, leading to high computational complexity and limited scalability. To address this challenge, this study introduces a deep learning network based on channel feature compression—partial channel selection sEMG net (PCS-EMGNet). This network combines channel feature compression (channel selection) and feature extraction (partial block), aiming to reduce the model’s parameter count while maintaining recognition accuracy. PCS-EMGNet extracts high-dimensional feature vectors from sEMG signals through the partial block, decoding spatial and temporal feature information. Subsequently, channel selection compresses and filters these high-dimensional feature vectors, accurately selecting channel features to reduce the model’s parameter count, thereby decreasing computational complexity and enhancing the model’s processing speed. Moreover, the proposed method ensures the stability of classification, further improving the model’s capability of recognizing features in sEMG signal data. Experimental validation was conducted on five benchmark databases, namely the NinaPro DB4, NinaPro DB5, BioPatRec DB1, BioPatRec DB2, and BioPatRec DB3 datasets. Compared to traditional gesture recognition methods, PCS-EMGNet significantly enhanced recognition accuracy and computational efficiency, broadening its application prospects in real-world settings. The experimental results showed that our model achieved the highest average accuracy of 88.34% across these databases, marking a 9.96% increase in average accuracy compared to models with similar parameter counts. Simultaneously, our model’s parameter size was reduced by an average of 80% compared to previous gesture recognition models, demonstrating the effectiveness of channel feature compression in maintaining recognition accuracy while significantly reducing the parameter count.

With the progression of tumor treatment, the 5-year survival rate of breast cancer is close to 90%. Cardiovascular toxicity caused by chemotherapy has become a vital factor affecting the survival of patients with breast cancer. Anthracyclines, such as doxorubicin, are still some of the most effective chemotherapeutic agents, but their resulting cardiotoxicity is generally considered to be progressive and irreversible. In addition to anthracyclines, platinum- and alkyl-based antitumor drugs also demonstrate certain cardiotoxic effects. Targeted drugs have always been considered a relatively safe option. However, in recent years, some random clinical trials have observed the occurrence of subclinical cardiotoxicity in targeted antitumor drug users, which may be related to the effects of targeted drugs on the angiotensin converting enzyme, angiotensin receptor and β receptor. The use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and beta-blockers may prevent clinical cardiotoxicity. This article reviews the toxicity and mechanisms of current clinical anti-breast cancer drugs and proposes strategies for preventing cardiovascular toxicity to provide recommendations for the clinical prevention and treatment of chemotherapy-related cardiomyopathy.

Background & Aims: OATP1B3/SLCO1B3 is a human liver-specific transporter for the clearance of endogenous compounds (eg, bile acid [BA]) and xenobiotics. The functional role of OATP1B3 in humans has not been characterized, as SLCO1B3 is poorly conserved among species without mouse orthologs. Methods: Slc10a1-knockout (Slc10a1-/-), Slc10a1hSLCO1B3 (endogenous mouse Slc10a1 promoter-driven human-SLCO1B3 expression in Slc10a1-/- mice), and human SLCO1B3 liver-specific transgenic (hSLCO1B3-LTG) mice were generated and challenged with 0.1% ursodeoxycholic-acid (UDCA), 1% cholic-acid (CA) diet, or bile duct ligation (BDL) for functional studies. Primary hepatocytes and hepatoma-PLC/RPF/5 cells were used for mechanistic studies. Results: Serum BA levels in Slc10a1-/- mice were substantially increased with or without 0.1% UDCA feeding compared with wild-type (WT) mice. This increase was attenuated in Slc10a1hSLCO1B3-mice, indicating that OATP1B3 functions as a significant hepatic BA uptake transporter. In vitro assay using primary hepatocytes from WT, Slc10a1-/-, and Slc10a1hSLCO1B3-mice indicated that OATP1B3 has a similar capacity in taking up taurocholate/TCA as Ntcp. Furthermore, TCA-induced bile flow was significantly impaired in Slc10a1-/- mice but partially recovered in Slc10a1hSLC01B3-mice, indicating that OATP1B3 can partially compensate the NTCP function in vivo. Liver-specific overexpression of OATP1B3 markedly increased the level of hepatic conjugated BA and cholestatic liver injury in 1% CA-fed and BDL mice. Mechanistic studies revealed that conjugated BAs stimulated Ccl2 and Cxcl2 in hepatocytes to increase hepatic neutrophil infiltration and proinflammatory cytokine production (eg, IL-6), which activated STAT3 to repress OATP1B3 expression by binding to its promoter. Conclusions: Human OATP1B3 is a significant BA uptake transporter and can partially compensate Ntcp for conjugated BA uptake in mice. Its downregulation in cholestasis is an adaptive protective response.

Abstract Systemic identification of tumor suppressor genes (TSGs) and elucidation of their signaling provide a new angle for understanding of tumorigenesis, which is important for developing successful treatment for lung cancer patients. In our current work, we conducted an in vivo screen for lung cancer TSGs through CRISPR/Cas9 mediated knockout of genes at genome-wide scale. We found that ZNF24 was a potent and clinically relevant TSG of lung cancer. Ectopic expression of ZNF24 arrested lung cancer cells in S phase. Mechanistically, ZNF24 bound to promoter region of P65 to negatively regulate its transcription and thereby the signaling activity of NF-κB pathway. This signaling cascade is clinically relevant. Importantly, we found that combinational inhibition of KRAS, NF-κB, and PD-1 effectively shrank autochthonous Kras G12D/ZNF24 −/− lung cancers in transgenic mouse model. Our current work thus revealed an important role played by loss of function of ZNF24 in lung tumorigenesis and shed new light in precision medicine for a portion of lung cancer patients.

Abstract Background: Bipolar disorder (BD) and schizophrenia (SC) have many similarities in clinical manifestations. The acute phase of BD has psychotic symptoms, while SC also has emotional symptoms during the onset, which suggests that there is some uncertainty in distinguishing BD and SC through clinical symptoms. Aim: To explore the characteristics of brain functional activities and cognitive impairment between BD and SC. Methods: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test was performed on patients in drug-naïve BD and SC (50 subjects in each group), and resting-state functional magnetic resonance imaging (rs-fMRI) scanning was performed meanwhile. Rs-fMRI data were routinely preprocessed, and the value of the fractional amplitude of low-frequency fluctuation (fALFF) was calculated. Then each part of the scores of the RBANS and the characteristics of brain function activities were compared between the two groups. Finally used Pearson correlation to analyze the correlation between cognition and brain function. Results: (1) Compared with BD group, all parts of RBANS scores in SC group decreased; (2) The left inferior occipital gyrus (IOG, peak coordinates − 30, -87, -15; t = 4.78, voxel size = 31, Alphasim correction) and the right superior temporal gyrus (STG, peak coordinates 51, -12, 0; t = 5.08, voxel size = 17, AlphaSim correction) were the brain areas with significant difference in fALFF values between BD and SC. Compared with SC group, the fALFF values of the left IOG and the right STG in BD group were increased (p

Abstract Background Sialic acid is often the distal sugar on glycoconjugates, and sialidases are enzymes that remove this sugar. In fibrotic lesions in human and mouse lungs, there is extensive desialylation of glycoconjugates, and upregulation of sialidases including the extracellular sialidase NEU3. In the bleomycin model of pulmonary fibrosis, mice lacking NEU3 (Neu3 −/− ) showed strongly attenuated bleomycin-induced weight loss, lung damage, inflammation, and fibrosis. This indicates that NEU3 is necessary for the full spectrum of bleomycin-induced pulmonary fibrosis. Methods To determine if NEU3 is sufficient to induce pulmonary fibrosis, recombinant murine NEU3 and a mutated inactive recombinant murine NEU3 protein were produced. Mice were given recombinant NEU3 proteins by oropharyngeal aspiration, either alone or 10 days after bleomycin challenge. Over the course of 21 days, mice were assessed for weight change, and after euthanasia, bronchoalveolar lavage fluid cells and lung tissue were assessed for inflammation and fibrosis. Results Aspiration of recombinant murine NEU3 caused inflammation and fibrosis in the lungs, while inactive NEU3 caused inflammation but not fibrosis. Mice were also treated with recombinant murine NEU3 starting 10 days after bleomycin. In male but not female mice, recombinant murine NEU3 increased inflammation and fibrosis. Inactive NEU3 did not enhance bleomycin-induced lung fibrosis. Conclusion These results suggest that NEU3 is sufficient to induce fibrosis in the lungs, that aspiration of NEU3 has a greater effect on male mice, and that this effect is mediated by NEU3’s enzymic activity.

Qinghai–Tibet Plateau is considered a region vulnerable to the effects of climate change. Studying the effects of climate change on the structure and function of soil microbial communities will provide insight into the carbon cycle under climate change. However, to date, changes in the successional dynamics and stability of microbial communities under the combined effects of climate change (warming or cooling) remain unknown, which limits our ability to predict the consequences of future climate change. In this study, in situ soil columns of an Abies georgei var. smithii forest at 4,300 and 3,500 m elevation in the Sygera Mountains were incubated in pairs for 1 year using the PVC tube method to simulate climate warming and cooling, corresponding to a temperature change of ±4.7°C. Illumina HiSeq sequencing was applied to study alterations in soil bacterial and fungal communities of different soil layers. Results showed that warming did not significantly affect the fungal and bacterial diversity of the 0–10 cm soil layer, but the fungal and bacterial diversity of the 20–30 cm soil layer increased significantly after warming. Warming changed the structure of fungal and bacterial communities in all soil layers (0–10 cm, 10–20 cm, and 20–30 cm), and the effect increased with the increase of soil layers. Cooling had almost no significant effect on fungal and bacterial diversity in all soil layers. Cooling changed the structure of fungal communities in all soil layers, but it showed no significant effect on the structure of bacterial communities in all soil layers because fungi are more adapted than bacteria to environments with high soil water content (SWC) and low temperatures. Redundancy analysis (RDA) and hierarchical analysis showed that changes in soil bacterial community structure were primarily related to soil physical and chemical properties, whereas changes in soil fungal community structure primarily affected SWC and soil temperature (Soil Temp). The specialization ratio of fungi and bacteria increased with soil depth, and fungi were significantly higher than bacteria, indicating that climate change has a greater impact on microorganisms in deeper soil layers, and fungi are more sensitive to climate change. Furthermore, a warmer climate could create more ecological niches for microbial species to coexist and increase the strength of microbial interactions, whereas a cooler climate could have the opposite effect. However, we found differences in the intensity of microbial interactions in response to climate change in different soil layers. This study provides new insights to understand and predict future effects of climate change on soil microbes in alpine forest ecosystems.

China started to offer human papillomavirus (HPV) vaccines to females aged 9–45 years in 2016. However, there was a lack of reports about HPV vaccination coverage in a representative sample of females in China. Therefore, this study aimed to examine the current HPV coverage and associated factors among females aged 9–50 years in Shenzhen, China, based on administrative health records kept by community health centers. A multistage random sampling approach was used. The research team randomly selected 18 community health centers in Shenzhen, and 3118 health records of females aged 9–50 years were then randomly selected from these health centers. Among all participants, 18.7% received at least one dose of HPV vaccination. The highest coverage was observed among females aged 18–26 years (23.4%), followed by those aged 27–35 years (22.0%) and 36–45 years (20.2%). Such coverage was very low among females aged 9–17 years (4.6%) and those aged 46–50 years (3.2%). Among females aged 18 years or above, higher education level, having a family doctor, and permanent residency in Shenzhen were associated with higher HPV vaccination coverage, while older age and being married/divorced were negatively associated with coverage. The HPV vaccination coverage in Shenzhen was 18.7% and there is a strong need for improvement.

Enhancing information representation in electromyography (EMG) signals is pivotal for interpreting human movement intentions. Traditional methods often concentrate on specific aspects of EMG signals, such as the time or frequency domains, while overlooking spatial features and hidden human motion information that exist across EMG channels. In response, we introduce an innovative approach that integrates multiple feature domains, including time, frequency, and spatial characteristics. By considering the spatial distribution of surface electromyographic electrodes, our method deciphers human movement intentions from a multidimensional perspective, resulting in significantly enhanced gesture recognition accuracy. Our approach employs a divide-and-conquer strategy to reveal connections between different muscle regions and specific gestures. Initially, we establish a microscopic viewpoint by extracting time-domain and frequency-domain features from individual EMG signal channels. We subsequently introduce a macroscopic perspective and incorporate spatial feature information by constructing an inter-channel electromyographic signal covariance matrix to uncover potential spatial features and human motion information. This dynamic fusion of features from multiple dimensions enables our approach to provide comprehensive insights into movement intentions. Furthermore, we introduce the space-to-space (SPS) framework to extend the myoelectric signal channel space, unleashing potential spatial information within and between channels. To validate our method, we conduct extensive experiments using the Ninapro DB4, Ninapro DB5, BioPatRec DB1, BioPatRec DB2, BioPatRec DB3, and Mendeley Data datasets. We systematically explore different combinations of feature extraction techniques. After combining multi-feature fusion with spatial features, the recognition performance of the ANN classifier on the six datasets improved by 2.53%, 2.15%, 1.15%, 1.77%, 1.24%, and 4.73%, respectively, compared to a single fusion approach in the time and frequency domains. Our results confirm the substantial benefits of our fusion approach, emphasizing the pivotal role of spatial feature information in the feature extraction process. This study provides a new way for surface electromyography-based gesture recognition through the fusion of multi-view features.

Potassium application can effectively mitigate the effects of drought stress on plant growth, and few studies have reported its application to the medicinal plant Salvia miltiorrhiza (S. miltiorrhiza). Four experimental treatments were used, including a control (Z1K0), non-drought potassium application (Z1K3), drought treatments (Z2K0), and drought-stress potassium application (Z2K3). The findings revealed that, in contrast to Z2K0, Z2K3 promoted the absorption of potassium in S. miltiorrhiza, elicited the aggregation of osmoregulatory compounds such as soluble protein and proline, and mitigated membrane impairment as a defense against the deleterious consequences of drought stress. Additionally, we extended our investigation to encompass comprehensive metabolomics analysis of the roots. Interestingly, subsequent root metabolomics analyses demonstrated that the drought application of potassium not only significantly reduced the amino acid content, but also increased the amount of terpenoids and phenolic acids in the roots. Nonetheless, the application of a particular amount of K under moderate drought conditions promoted the growth and yield of S. miltiorrhiza, but proved to be detrimental to its active ingredients. Indeed, the findings of this study offer valuable insights and recommendations for the application of potassium to mitigate the impact of drought stress in S. miltiorrhiza and other medicinal plants.

Pulmonary fibrosis is potentiated by a positive feedback loop involving the extracellular sialidase enzyme neuraminidase 3 (NEU3) causing release of active TGF-β1 and TGF-β1 upregulating NEU3 by increasing translation without affecting mRNA levels. In this report, we elucidate the TGF-β1 upregulation of the translation mechanism. In human lung fibroblasts, TGF-β1 increased levels of proteins, including NEU3, by increasing translation of the encoding mRNAs without significantly affecting levels of these mRNAs. A total of 180 of these mRNAs shared a common 20-nucleotide motif. Deletion of this motif from NEU3 mRNA eliminated the TGF-β1 upregulation of NEU3 translation, while insertion of this motif in 2 mRNAs insensitive to TGF-β1 caused TGF-β1 to upregulate their translation. RNA-binding proteins including DEAD box helicase 3, X-linked (DDX3), bind the RNA motif, and TGF-β1 regulates their protein levels and/or binding to the motif. We found that DDX3 was upregulated in the fibrotic lesions in patients with pulmonary fibrosis, and inhibiting DDX3 in fibroblasts reduced TGF-β1 upregulation of NEU3 levels. In the mouse bleomycin model of pulmonary fibrosis, injections of the DDX3 inhibitor RK-33 potentiated survival and reduced lung inflammation, fibrosis, and tissue levels of DDX3, TGF-β1, and NEU3. These results suggest that inhibiting an mRNA-binding protein that mediates TGF-β1 upregulation of translation can reduce pulmonary fibrosis.

T-cell acute lymphoblastic leukemia (T-ALL) has a poor prognosis as a result of severe immunosuppression and rapid tumor progression with resistance to conventional chemotherapy. Excessive IgD may play a role in T cell activation via IgD Fc receptor (FcδR). Here we aimed to investigate the effects of IgD in T-ALL and demonstrated the potential benefit by targeting IgD/FcδR in T-ALL patients with IgD-Fc-Ig fusion protein. In T-ALL patients’ blood samples and cell lines, the level of IgD, the percentage of FcδR expressing cells and the binding affinity were determined by flow cytometry. T cell viability, proliferation and apoptosis were analyzed. A mouse xenograft model was used to evaluate the in vivo effect of IgD-Fc-Ig, an IgD-FcδR blocker. The levels of serum IgD and FcδR were abnormally increased in part of T-ALL patients and IgD could induce over-proliferation and inhibit apoptosis of T-ALL cells in vitro. FcδR was constitutively expressed on T-ALL cells. IgD-Fc-Ig showed similar binding affinity to FcδR and selectively blocked the stimulation effect of IgD on T-ALL cells in vitro. In vivo study exhibited that IgD-Fc-Ig may also have therapeutic benefit. IgD-Fc-Ig administration inhibited human T-ALL growth and extended survival in xenograft T-ALL mice. In conclusion, this work supports the idea of targeting IgD/FcδR in T-ALL patients with excessive IgD. IgD-Fc-Ig fusion protein might be a potential biological drug with high selectivity for T-ALL treatment.

Abstract Background Obesity is a serious worldwide public health problem, especially for people with mental disorders. Aim To explore the related factors of obesity by analyzing the metabolic indexes of patients with common mental disorders in stable stage. Methods Five hundred seventy-six subjects with major depressive disorder (MDD), bipolar disorder (BD) or schizophrenia (SCZ) were included, who received fixed drug dose and routine drug treatment for 2 years or more. Their venous blood was collected, and the blood metabolic indexes were analyzed. Results BD and SCZ are more prone to obesity than MDD. Multiple linear regression analysis showed that the value of BMI increased with the increase of age(B = 0.084, p

In this paper, the Gilson–Pickering (GP) equation with applications for wave propagation in plasma physics and crystal lattice theory is studied. The model with wave propagation in plasma physics and crystal lattice theory is explained. A collection of evolution equations from this model, containing the Fornberg–Whitham, Rosenau–Hyman, and Fuchssteiner–Fokas–Camassa–Holm equations is developed. The descriptions of new waves, crystal lattice theory, and plasma physics by applying the standard tan(ϕ/2)-expansion technique are investigated. Many alternative responses employing various formulae are achieved; each of these solutions is represented by a distinct plot. Some novel solitary wave solutions of the nonlinear GP equation are constructed utilizing the Paul–Painlevé approach. In addition, several solutions including soliton, bright soliton, and periodic wave solutions are reached using He’s variational direct technique (VDT). The superiority of the new mathematical theory over the old one is demonstrated through theorems, and an example of how to design and numerically calibrate a nonlinear model using closed-form solutions is given. In addition, the influence of changes in some important design parameters is analyzed. Our computational solutions exhibit exceptional accuracy and stability, displaying negligible errors. Furthermore, our findings unveil several unprecedented solitary wave solutions of the GP model, underscoring the significance and novelty of our study. Our research establishes a promising foundation for future investigations on incompressible fluids, facilitating the development of more efficient and accurate models for predicting fluid behavior.

BackgroundThis study aimed to investigate the relationships between regional neural activity and multiple related indicators in patients with major depressive disorder (MDD).MethodsForty-two patients and 42 healthy controls (HCs) were enrolled. Pearson/Spearman correlation analyses were applied to examine the associations between abnormal regional homogeneity (ReHo) and different indicators in the patients.ResultsCompared with HCs, patients with MDD had increased ReHo in the left inferior temporal gyrus (ITG) and decreased ReHo values in the left putamen, anterior cingulate cortex (ACC), and precentral gyrus. The ReHo of the left putamen was positively correlated with the PR interval, Repeatable Battery for the Assessment of Neuropsychological Status 4A, and Discriminant analysis (D), and negatively correlated with Ae (block) and Ae (total) in the patients. The ReHo value of the left ACC was positively correlated with the severity of depression, Stroop Color Word Test of C − 2B + 100 in reaction time, and negatively correlated with Ce (Missay) and Perseverative Responses in the patients. The ReHo of the left ITG was positively correlated with the Neuroticism scores and negatively correlated with the Lie scores in the patients.ConclusionThese results suggested that the decreased ReHo of the salience network might be the underpinning of cognitive impairments in patients with MDD.

The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae), is a key vector of the causal agents of Huanglongbing (HLB), a devastating disease affecting citrus almost worldwide. Nicotiana tabacum L. is an important commercial crop in China. Field observations suggested that D. citri adults die on N. tabacum leaves when grown nearby citrus orchards. In this study, the preference for and survivorship of D. citri adults on N. tabacum and their feeding behavior were investigated. The results showed that D. citri adults were attracted to N. tabacum and to the green leaf volatiles (GLVs) (Z)-3-hexenol and (E)-2-hexenol. The survival of D. citri adults on N. tabacum was less than 30 h, which was shorter than that for adults without food (35 h) and on a suitable host Murraya exotica L. (29 days). Electrical penetration graph (EPG) recordings revealed that the pathway phase of D. citri on N. tabacum leaves consisted of four waveforms—the non-probing phase (NP), the pathway phase (PP, including intercellular probing of activity in the phloem (C) and phloem penetration (D)), phloem salivation (E1), and phloem ingestion (E2). Diaphorina citri only secreted saliva and ingested sap from phloem on N. tabacum leaves and spent the longest duration in phloem sap ingestion (E2). Moreover, L-nicotine, an important defense compound against insects in N. tabacum plants, was highly toxic to D. citri. These results suggested that N. tabacum plants could help to sustainably control the spread of D. citri and HLB when growing in and around citrus orchards.

Abstract Background A thermal face recognition under different conditions is proposed in this article. The novelty of the proposed method is applying temperature information in the recognition of thermal face. The physiological information is obtained from the face using a thermal camera, and a machine learning classifier is utilized for thermal face recognition. The steps of preprocessing, feature extraction and classification are incorporated in training phase. First of all, by using Bayesian framework, the human face can be extracted from thermal face image. Several thermal points are selected as a feature vector. These points are utilized to train Random Forest (RF). Random Forest is a supervised learning algorithm. It is an ensemble of decision trees. Namely, RF merges multiple decision trees together to obtain a more accurate classification. Feature vectors from the testing image are fed into the classifier for face recognition. Results Experiments were conducted under different conditions, including normal, adding noise, wearing glasses, face mask, and glasses with mask. To compare the performance with the convolutional neural network-based technique, experimental results of the proposed method demonstrate its robustness against different challenges. Conclusions Comparisons with other techniques demonstrate that the proposed method is robust under less feature points, which is around one twenty-eighth to one sixtieth of those by other classic methods.

BackgroundWith increasing evidence suggesting potential benefits, acupuncture is often applied to the treatment of premature ventricular complexes (PVCs), particularly in symptomatic patients who fail or are unsuitable for medications or refuse catheter ablation. However, the existing clinical evidence is inconsistent.ObjectivesThis review aims to systematically evaluate the effectiveness and safety of acupuncture therapies for PVCs without ischemic or structural heart diseases, when it is compared with sham/placebo acupuncture or usual care, or used as an add-on therapy to routine care; and to summarize existing pre-clinical research evidence supporting the effects of acupuncture therapies for this clinical condition.MethodsFour English-language databases, four Chinese-language databases and seven clinical registries were searched from their inceptions to May 21, 2021 and updated to November 01, 2022. Trials comparing acupuncture with sham acupuncture or evaluating the add-on effects of acupuncture were included. Primary outcomes are the number of premature ventricular beats (PVBs) and effective rate defined as “the proportion of participants with over 50% decrease in the number of PVBs from baseline to the end of treatment measured by 24-h Holter”.ResultsA total of 479 records were identified with nine trials involving 847 participants included in this review. Meta-analysis on two sham-control trials with low risk of bias for all domains suggested that acupuncture could significantly reduce the number of PVBs (RR 3.83, 95% CI [2.19, 6.7], I2 = 0%). Moreover, the combination of acupuncture and standard treatment was superior to standard treatment alone in reducing the burden of PVBs (RR 1.21, 95% CI [1.08, 1.36], I2 = 0%). Though no treatment protocol consensus was announced, body acupuncture on point PC6, HT7, DU10, DU11, and ST36 with duration of needle retention ranging from 15 to 30 min for a 4-week treatment period is broadly used by the included trials. For experimental evidence, five studies explored the mechanisms of acupuncture for PVCs were eventually included into analysis and PC6 was the most frequently studied acupuncture point. Moreover, a reduction of electrical activity of sympathetic nerves in experimental animals undergoing electro-acupuncture was observed by four of these studies.ConclusionSham-controlled RCT evidence with moderate-level certainty suggested that acupuncture could be a therapeutic option to reduce the burden of PVBs in patients without ischemic or structural heart diseases. Further clinical studies using validated and reliable outcome measurement instruments and bench research to unveil the mechanisms of acupuncture stimulation and point-specific effects for PVCs are needed.Systematic review registration[https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=262132], identifier [CRD42021262132].

ObjectivesEvidence from systematic reviews/meta-analyses about the efficacy and safety of Qishen Yiqi (QSYQ) dripping pills in chronic heart failure (CHF) remains unclear. This study comprehensively reviewed available systematic reviews on latest evidence to provide reliable information for the clinical use of QSYQ in CHF.MethodsThe systematic review was performed on studies retrieved from six major medical databases. Eligible studies were evaluated in terms of methodological quality and quality of evidence using the Assessment of Multiple Systematic review 2 (AMSTAR-2) tool, the Risk of Bias in Systematic Reviews (ROBIS) was used to assess the risk of bias, and the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) 2020 was utilized for assessing reporting quality. In addition, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to determine primary outcome indicators’ evidence quality.ResultsA total of 14 systematic reviews were included in this study, based on which it could be concluded that QSYQ combined with conventional medicine (CM) treatment tended to be superior to CM treatment alone in terms of improving cardiac function-related indices (e.g., increasing the left ventricular ejection fraction [LVEF] and reducing the left ventricular end-diastolic dimension [LVEDD] and left ventricular end-systolic internal diameter [LVESD]), improving the total effective rate and 6-min walking distance (6MWD), and reducing N-terminal pro-brain natriuretic peptide (NT-proBNP). Overall, no serious QSYQ-related adverse events were observed. However, the GRADE results showed “very low” to “moderate” evidence for these outcomes, with no high-quality evidence supporting them. Unsatisfactory results were obtained in terms of methodological quality, risk of bias and reporting quality after assessment using the AMSTAR-2, ROBIS, and PRISMA 2020, limited mainly by deficiencies in the following areas: registration of study protocols, explanation of the inclusion of randomized controlled trials (RCTs), complete and detailed search strategy, list of excluded literature, description of funding sources for inclusion in RCTs, investigation of the impact of risk of bias on the results of meta-analysis, and reporting of potential conflicts of interest.ConclusionThe efficacy and safety of QSYQ adjuvant therapy in CHF remain to be further clarified due to the lack of high-quality evidence provided by current systematic reviews.

Bile components play a critical role in maintaining gut microbiota homeostasis. In cholestasis, bile secretion is impaired, leading to liver injury. However, it remains to be elucidated whether gut microbiota plays a role in cholestatic liver injury. Here, we performed a sham operation and bile duct ligation (BDL) in antibiotic-induced microbiome depleted (AIMD) mice and assessed liver injury and fecal microbiota composition in these mice. Significant reductions in gut microbiota richness and diversity were found in AIMD-sham mice when compared to sham controls. Three-day BDL leads to great elevation of plasma ALT, ALP, total bile acids, and bilirubin where reduced diversity of the gut microbiota was also found. AIMD further aggravated cholestatic liver injury evidenced by significantly higher levels of plasma ALT and ALP, associated with further reduced diversity and increased Gram-negative bacteria in gut microbiota. Further analyses revealed increased levels of LPS in the plasma of AIMD-BDL mice where elevated expression of inflammatory genes and decreased expression of hepatic detoxification enzymes were also found in liver when compared to the BDL group. These findings indicate that gut microbiota plays a critical role in cholestatic liver injury. Maintaining its homeostasis may alleviate liver injury in patients with cholestasis.

An earthquake emergency command system is designed based on cloud computing and the Internet of Things (IoT) to mitigate slow information acquisition, low processing efficiency, and weak information storage and communication ability in earthquake rescue. First, cloud computing technology is introduced, and a traditional earthquake emergency command system is analyzed comprehensively. Then, the characteristics of midwave infrared remote sensing data are explored before and after recent earthquakes in China based on satellite remote sensing data. Subsequently, a new earthquake emergency command system is built based on cloud computing and IoT technology along with data from satellite midwave infrared remote sensing. Finally, system feasibility is evaluated. The results show that surface radiation changes significantly before an earthquake; infrared brightness and temperature fluctuates drastically; and the abnormal region gradually approaches the epicenter of the earthquake. The peak value of the relative power spectrum in the earthquake is more than 9 times the average. In conclusion, the proposed emergency command system based on satellite remote sensing data, cloud computing, and IoT can yield good evaluation results (5.36), demonstrating that multidimensional satellite thermal infrared remote sensing data analysis can improve the accuracy of earthquake prediction. The proposed earthquake emergency command system based on satellite remote sensing data combined with cloud computing and IoT technology can also provide a basis for optimizing earthquake rescue strategies.

Gas clusters can reprove the sewage ability of flame-permeability char joint, but the interaction motion between proposed vapor molecules and gasoline-confine charcoal during the wind enema advance is still unclear. For this consideration, supported by the surface assimilation figure of qualifier-enclose char, the magnificent orthodox whole Monte Carlo (GCMC) manner was interesting to ponder the elution conduct of CH4 in the wind-confine charcoal configuration after the farding bag of N2/CO2 under distinct enema stamp. The clockwork of N2/C advances the elution of CH4 in charcoal. The examination ensues showed the following: (1) Compared with the enema of N2, the gasoline-restrain charcoal has more familiar CH4 molecules after CO2 enema, and the constituting force of the CH4-CO2 system is everywhere more humble than that of the CH4-N2 system, the former is more fix. (2) In the same enema pattern, obtained with the CH4-N2 system, the CH4 grout indicated more regular distribution in the CH4-CO2 system. CH4 heptane is more active, the expansion cooperation of CH4 in the CH4-CO2 system is more, and the effect of CO2 in promoting the elution of CH4 is better. (3) After CO2/N2 is interjected into the fart-hold charcoal construction, as the enema compression extension, the referring concentrations of CO2, N2, and CH4 in the coping wax, the opposite to major of CH4 in the CH4-CO2 system is the zenith everywhere. In the CH4—N2 system, the opposite to major of CO2 in the CH4 and CH4—CO2 system is in the centric, and the opposite to major of N2 in the CH4—N2 system is the lowermost. (4) The reasonably enema affliction for N2 to raise CH4 elution is between 2 and 4 MPa, and CO2 is honest to advance CH4 elution. The enema urgency is between 3 and 4 MPa. Based on this data, methane extraction and resource utilization can be improved to a certain extent. The result has shown that the inquiry effect can condition speculative uphold for the research studies of char cicatrix petrol enema irritation technology.

BackgroundInsomnia is the most common of the sleep disorders. Current pharmacotherapy treatment options are usually associated with adverse effects and withdrawal phenomena. Therapeutic alternatives with a more favorable safety profile for patients are needed. Mongolian medical warm acupuncture (MMWA) is an emerging therapeutic option for treating insomnia. However, the underlying mechanisms responsible for the anti-insomnia efficacy of the MMWA remain unclear. This study aims to investigate the effect of the MMWA on the alterations of the gut microbiota and serum metabolome in rats with insomnia.ResultsWe found that the relative abundances of gut bacteria and the concentrations of several serum metabolites were obviously altered in PCPA-induced insomnia rats. The MMWA treatment exerted an anti-insomnia effect. In addition, the dysbiosis of the gut microbiota and the serum metabolites were ameliorated by the MMWA. Correlation analysis between the gut microbiota and metabolites suggested that the levels of Amide c18, Benzoyl chloride, Cytosine, and N, n-dimethylarginine were positively correlated with the relative abundance of Clostridium XlVa and Blautia, which characterized the insomnia rats. KEGG enrichment analysis identified the cAMP signaling pathway involving anti-insomnia effect of the MMWA. Moreover, the MMWA intervention significantly increased contents of butyrate in feces, while effectively inhibited the expression level of GAT-1 in brain tissues.ConclusionThis study reveals that the MMWA intervention might have a major impact on the modulation of host gut microbiota and metabolites, which in turn have a crucial role in the regulation of the host's signaling pathways associated with insomnia. The present study could provide useful ideas for the study of the intervention mechanisms of the MMWA in insomnia rat models.

Abstract Impressive clinical benefit is seen in clinic with PD‐1 inhibitors on portion of cancer patients. Yet, there remains an urgent need to develop effective synergizers to expand their clinical application. Tumor‐associated macrophage (TAM), a type of M2‐polarized macrophage, eliminates or suppresses T‐cell‐mediated anti‐tumor responses. Transforming TAMs into M1 macrophages is an attractive strategy of anti‐tumor therapy. Here, we conducted a high‐throughput screening and found that Carfilzomib potently drove M2 macrophages to express M1 cytokines, phagocytose tumor cells, and present antigens to T cells. Mechanistically, Carfilzomib elicited unfolded protein response (UPR), activated IRE1α to recruit TRAF2, and activated NF‐κB to transcribe genes encoding M1 markers in M2 macrophages. In vivo, Carfilzomib effectively rewired tumor microenvironment through reprogramming TAMs into M1‐like macrophages and shrank autochthonous lung cancers in transgenic mouse model. More importantly, Carfilzomib synergized with PD‐1 antibody to almost completely regress autochthonous lung cancers. Given the safety profiles of Carfilzomib in clinic, our work suggested a potentially immediate application of combinational treatment with Carfilzomib and PD‐1 inhibitors for patients with solid tumors.

Fibrosing diseases are a major medical problem, and are associated with more deaths per year than cancer in the US. Sialidases are enzymes that remove the sugar sialic acid from glycoconjugates. In this review, we describe efforts to inhibit fibrosis by inhibiting sialidases, and describe the following rationale for considering sialidases to be a potential target to inhibit fibrosis. First, sialidases are upregulated in fibrotic lesions in humans and in a mouse model of pulmonary fibrosis. Second, the extracellular sialidase NEU3 appears to be both necessary and sufficient for pulmonary fibrosis in mice. Third, there exist at least three mechanistic ways in which NEU3 potentiates fibrosis, with two of them being positive feedback loops where a profibrotic cytokine upregulates NEU3, and the upregulated NEU3 then upregulates the profibrotic cytokine. Fourth, a variety of NEU3 inhibitors block pulmonary fibrosis in a mouse model. Finally, the high sialidase levels in a fibrotic lesion cause an easily observed desialylation of serum proteins, and in a mouse model, sialidase inhibitors that stop fibrosis reverse the serum protein desialylation. This then indicates that serum protein sialylation is a potential surrogate biomarker for the effect of sialidase inhibitors, which would facilitate clinical trials to test the exciting possibility that sialidase inhibitors could be used as therapeutics for fibrosis.

Background: The coronavirus disease 2019 (COVID-19) pandemic has severely affected healthcare systems around the world. This study aimed to investigate the perceptions of cardiologists regarding how the COVID-19 pandemic has affected the clinical practice patterns for acute coronary syndrome (ACS). Methods: A multicenter clinician survey was sent to 300 cardiologists working in 22 provinces in China. The survey collected demographic information and inquired about their perceptions of how the COVID-19 pandemic has affected ACS clinical practice patterns. Results: The survey was completed by 211 (70.3%) cardiologists, 82.5% of whom were employed in tertiary hospitals, and 52.1% reported more than 10 years of clinical cardiology practice. Most respondents observed a reduction in ACS inpatients and outpatients in their hospitals during the pandemic. Only 29.9% of the respondents had access to a dedicated catheter room for the treatment of COVID-19-positive ACS patients. Most respondents stated that the COVID-19 pandemic had varying degrees of effect on the treatment of acute ST-segment elevation myocardial infarction (STEMI), acute non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina. Compared with the assumed non-pandemic period, in the designed clinical questions, the selection of coronary interventional therapy for STEMI, NSTEMI, and unstable angina during the COVID-19 pandemic was significantly decreased (all p < 0.05), and the selection of pharmacotherapy was increased (all p < 0.05). The selection of fibrinolytic therapy for STEMI during the pandemic was higher than in the assumed non-pandemic period (p < 0.05). Conclusions: The COVID-19 pandemic has profoundly affected ACS clinical practice patterns. The use of invasive therapies significantly decreased during the pandemic period, whereas pharmacotherapy was more often prescribed by the cardiologists.

Lung cancer is the leading cause of cancer-related deaths worldwide. Tumor suppressor genes (TSGs) play a critical role in restricting tumorigenesis and impact the therapeutic effect of various treatments. However, TSGs remain to be systemically determined in lung cancer. Here, we identified GATA6 as a potent lung cancer TSG. GATA6 inhibited lung cancer cell growth in vitro and tumorigenesis in vivo. Mechanistically, GATA6 upregulated p53 and p21 mRNA while it inhibited AKT activation to stabilize p21 protein, thus inducing lung cancer cell senescence. Furthermore, we showed that ectopic expression of GATA6 led to dramatic slowdown of growth rate of established lung tumor xenograft in vivo.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and T cell hyper-activation. Emerging evidence has shown that the stimulation of immunoglobulin D (IgD) induces T cell activation and may contribute to disease pathogenesis. In this study, the sIgD concentrations were positively associated with disease activity score in 28 joints (DAS28) and anti-cyclic citrullinated peptide (anti-CCP) in RA. We demonstrated that IgD-Fc-Ig (composed of human IgD Fc domain and IgG1 Fc domain, obtained through prokaryotic protein expression and chromatography purification) effectively inhibited the activation and proliferation of T cells in healthy controls and PBMCs in RA patients stimulated by IgD, recovered the Th17/Treg cell subset balance, and downregulated p-Lck and p-ZAP70 expression. Moreover, in vivo, IgD-Fc-Ig decreased the swollen joint counts and arthritis indices in mice with collagen-induced arthritis (CIA), and ameliorated histopathological changes in joint and spleen tissue. It also downregulated thymocyte proliferation and reduced the percentage of helper T cells (Th) and CD154+ T cells, reversed the imbalance of Th1/Th2 and Th17/Treg cell subsets, reduced cytokine and chemokine levels, and inhibited p-Lck and p-ZAP70 expression. Our data suggest that IgD-Fc-Ig fusion protein regulates T cell activity in RA. These findings have potential implications for IgD-targeted strategies to treat IgD-associated RA.

Background Laboratory studies demonstrate glucose‐insulin‐potassium (GIK) as a potent cardioprotective intervention, but clinical trials have yielded mixed results, likely because of varying formulas and timing of GIK treatment and different clinical settings. This study sought to evaluate the effects of modified GIK regimen given perioperatively with an insulin‐glucose ratio of 1:3 in patients undergoing cardiopulmonary bypass surgery. Methods and Results In this prospective, randomized, double‐blinded trial with 930 patients referred for cardiac surgery with cardiopulmonary bypass, GIK (200 g/L glucose, 66.7 U/L insulin, and 80 mmol/L KCl) or placebo treatment was administered intravenously at 1 mL/kg per hour 10 minutes before anesthesia and continuously for 12.5 hours. The primary outcome was the incidence of in‐hospital major adverse cardiac events including all‐cause death, low cardiac output syndrome, acute myocardial infarction, cardiac arrest with successful resuscitation, congestive heart failure, and arrhythmia. GIK therapy reduced the incidence of major adverse cardiac events and enhanced cardiac function recovery without increasing perioperative blood glucose compared with the control group. Mechanistically, this treatment resulted in increased glucose uptake and less lactate excretion calculated by the differences between arterial and coronary sinus, and increased phosphorylation of insulin receptor substrate‐1 and protein kinase B in the hearts of GIK‐treated patients. Systemic blood lactate was also reduced in GIK‐treated patients during cardiopulmonary bypass surgery. Conclusions A modified GIK regimen administered perioperatively reduces the incidence of in‐hospital major adverse cardiac events in patients undergoing cardiopulmonary bypass surgery. These benefits are likely a result of enhanced systemic tissue perfusion and improved myocardial metabolism via activation of insulin signaling by GIK. Clinical Trial Registration URL: clinicaltrials.gov. Identifier: NCT01516138.

Diaphorina citri Kuwayama is the most economically important citrus pest which is the primary vector of Candidatus Liberibacter spp. causing citrus greening (huanglongbing, HLB) disease. To better understand the developmental and structural changes of antennae and antennal sensilla in D. citri nymphs, we investigated the antennal morphology, structure and sensilla distribution of the five nymphal stages of D. citri using scanning electron microscopy. The antennae of the five different nymphal stages of D. citri were filiform in shape, which consisted of two segments in the first-, second- and third-instar nymphs; three segments in the fourth- and fifth-instar nymphs. The length of their antennae was significantly increased with the increase of the nymphal instar, as well as the total number of antennal sensilla. Ten morphological sensilla types were recorded altogether. They were the long terminal hair (TH1), short terminal hair (TH2), sensilla trichoidea (ST), cavity sensillum 1 (CvS1), cavity sensillum 2 (CvS2), sensilla basiconica 1-3 (SB1-3), sensilla campaniform (SCA) and partitioned sensory organ (PSO). Also, the distribution of antennal sensilla in each nymphal stage of D. citri was asymmetrical. The SBs only occurred on the antennae of the third-, fourth- and fifth-instar nymphs. Only one CvS2 was found in the third- and fifth-instar nymphs, and one SCA in the fourth- and fifth-instar nymphs, respectively. The possible roles of the nymphal antennal sensilla in D. citri were discussed. The results could contribute to a better understanding of the development of the sensory system, and facilitate future studies on the antennal functions in D. citri nymphs.

Speckle noise removal in medical ultrasound images is a challenging task. In this paper, a new model is proposed to removal speckle noise, alternating direction method of multipliers algorithm is employed to solve the new energy minimization model. The convexity, existence, and uniqueness of the new energy minimization model’s solution are proved. Series of experiments are designed in this paper. Numerical results show that the new algorithm can reduce the step effect effectively obtain good results in visual effect and quantitative measures by comparing with some traditional models.

Abstract Background Pentraxins are a family of highly conserved secreted proteins that regulate the innate immune system, including monocytes and macrophages. C-reactive protein (CRP) is a plasma protein whose levels can rise to 1000 μg/ml from the normal

Abstract BTK plays a critical role in the B cell receptor mediated inflammatory signaling in the rheumatoid arthritis (RA). Through a rational design approach we discovered a highly selective and potent BTK kinase inhibitor (CHMFL-BTK-11) which exerted its inhibitory efficacy through a covalent bond with BTK Cys481. CHMFL-BTK-11 potently blocked the anti-IgM stimulated BCR signaling in the Ramos cell lines and isolated human primary B cells. It significantly inhibited the LPS stimulated TNF-α production in the human PBMC cells but only weakly affecting the normal PBMC cell proliferation. In the adjuvant-induced arthritis rat model, CHMFL-BTK-11 ameliorated the inflammatory response through blockage of proliferation of activated B cells, inhibition of the secretion of the inflammatory factors such as IgG1, IgG2, IgM, IL-6 and PMΦ phagocytosis, stimulation of secretion of IL-10. The high specificity of CHMFL-BTK-11 makes it a useful pharmacological tool to further detect BTK mediated signaling in the pathology of RA.

Objective This study was performed to evaluate the clinical efficacy and safety of a novel surgical procedure in treating tracheal or bronchial compression related to severe congenital heart disease. Methods The clinical data of 28 patients with tracheal or bronchial compression related to severe congenital heart disease were retrospectively analyzed. In the control group, 12 patients underwent surgery for congenital cardiac malformations. In the treatment group, 16 patients underwent surgery for congenital cardiac malformations combined with partial resection of the pulmonary artery wall. The cardiothoracic ratio, pulmonary arterial pressure, left ventricular end-diastolic dimension, diameter of the pulmonary artery, and diameter of the trachea in the stenotic segment were quantitatively measured before and 9 days after the operation. Results The diameter of the pulmonary artery and diameter of the trachea in the stenotic segment were almost restored to the normal range in the treatment group. Patients in the treatment group recovered more rapidly and effectively than those in the control group. Conclusion Partial resection of the pulmonary artery wall is an efficacious and safe technique in the treatment of tracheal or bronchial compression related to severe congenital heart disease.

The present study was designed to test the hypothesis that exercise training elicited a cardioprotective effect against ischemia and reperfusion (I/R) via the κ-opioid receptor (κ-OR)-mediated signaling pathway. Rats were randomly divided into four groups: the control group, the moderate intensity exercise (ME) group, the high intensity exercise (HE) group, and the acute exercise (AE) group. For the exercise training protocols, the rats were subjected to one week of adaptive treadmill training, while from the second week, the ME and HE groups were subjected to eight weeks of exercise training, and the AE group was subjected to three days of adaptive treadmill training and one day of vigorous exercise. After these protocols, the three exercise training groups were divided into different treatment groups, and the rats were subjected to 30 min of ischemia and 120 min of reperfusion. Changes in infarct size and serum cTnT (cardiac troponin T) caused by I/R were reduced by exercise training. Moreover, cardiac dysfunction caused by I/R was also alleviated by exercise training. These effects of exercise training were reversed by nor-BNI (a selective κ-OR antagonist), Compound C (a selective AMPK inhibitor), Akt inhibitor and L-NAME (a non-selective eNOS inhibitor). Expression of κ-OR and phosphorylation of AMPK, Akt and eNOS were significantly increased in the ME, HE and AE groups. These findings demonstrated that the cardioprotective effect of exercise training is possibly mediated by the κ-OR-AMPK-Akt-eNOS signaling pathway.

Immunoglobulin D (IgD) is a surface immunoglobulin that is expressed as either membrane IgD (mIgD) or secreted IgD (sIgD). Researchers have shown that sIgD is often elevated in patients with autoimmune diseases. The possible roles of sIgD on the function of peripheral blood mononuclear cells (PBMCs) in rheumatoid arthritis (RA) are still unclear. In this study, we compared the expression of sIgD, mIgD and IgD receptor (IgDR) in RA patients and healthy controls, and investigated the effect of sIgD on the function of PBMCs. We found that the levels of sIgD, mIgD and IgDR were significantly higher in RA patients compared with healthy controls. The concentrations of sIgD were positively correlated with soluble receptor activator of nuclear factor-κB ligand (sRANKL), rheumatoid factor (RF) and C-reactive protein (CRP) in RA patients. Strikingly, IgD could enhance the proliferation of PBMCs and induce IL-1α, IL-1β, TNF-α, IL-6 and IL-10 production from PBMCs. Moreover, the percentage of activated T cell subsets (CD4+CD69+, CD4+CD154+) and activated B cell subsets (CD19+CD23+, CD19+CD21+, CD19+IgD+ and CD19-CD138+) were increased by IgD. The percentage of unactivated T cell subset (CD4+CD62L+) and immature B cell subset (CD19+IgM+IgD-) were decreased by IgD in PBMCs. Furthermore, the expressions of IgDR on T and B cells were significantly increased by treatment with IgD. Our results demonstrate that IgD enhanced the activation of PBMCs, which may contribute to RA pathogenesis. Therefore, IgD could be a potential novel immunotherapeutic target for the management of RA.

Myopia incidence in China is rapidly becoming a very serious sight compromising problem in a large segment of the general population. Therefore, delineating the underlying mechanisms leading to myopia will markedly lessen the likelihood of other sight compromising complications. In this regard, there is some evidence that patients afflicted with familial adenomatous polyposis (FAP), havean adenomatous polyposis coli (APC) mutation and a higher incidence of myopia. To clarify this possible association, we determined whether the changes in pertinent biometric and biochemical parameters underlying postnatal refractive error development in APCMin mice are relevant for gaining insight into the pathogenesis of this disease in humans. The refraction and biometrics in APCMin mice and age-matched wild-type (WT) littermates between postnatal days P28 and P84 were examined with eccentric infrared photorefraction (EIR) and customized optical coherence tomography (OCT). Compared with WT littermates, the APCMin mutated mice developed myopia (average -4.64 D) on P84 which was associated with increased vitreous chamber depth (VCD). Furthermore, retinal and scleral changes appear in these mice along with: 1) axial length shortening; 2) increased retinal cell proliferation; 3) and decreased tyrosine hydroxylase (TH) expression, the rate-limiting enzyme of DA synthesis. Scleral collagen fibril diameters became heterogeneous and irregularly organized in the APCMin mice. Western blot analysis showed that scleral alpha-1 type I collagen (col1α1) expression also decreased whereas MMP2 and MMP9 mRNA expression was invariant. These results indicate that defective APC gene function promotes refractive error development. By characterizing in APCMin mice ocular developmental changes, this approach provides novel insight into underlying pathophysiological mechanisms contributing to human myopia development.

Levels of bile acid metabolic enzymes and membrane transporters have been reported to change in cholestasis. These alterations (e.g. CYP7A1 repression and MRP4 induction) are thought to be adaptive responses that attenuate cholestatic liver injury. However, the molecular mechanisms of these adaptive responses in human obstructive cholestasis due to gallstone biliary obstruction remain unclear.We collected liver samples from cholestatic patients with biliary obstruction due to gallstones and from control patients without liver disease (n = 22 per group). The expression levels of bile acid synthetic and detoxification enzymes, membrane transporters, and the related nuclear receptors and transcriptional factors were measured.The levels of bile acid synthetic enzymes, CYP7B1 and CYP8B1, and the detoxification enzyme CYP2B6 were increased in cholestatic livers by 2.4-fold, 2.8-fold, and 1.9-fold, respectively (p

Prostaglandin (PG) analogs, including latanoprost, travoprost, and bimatoprost, are currently the most commonly used topical ocular hypotensive medications. The purpose of this study was to investigate the corneal alterations in rabbits following exposure to commercial solution of latanoprost, travoprost and bimatoprost. A total of 64 New Zealand albino rabbits were used and four groups of treatments were constituted. Commercial latanoprost, travoprost, bimatoprost or 0.02% benzalkonium chloride (BAK) was applied once daily to one eye each of rabbits for 30 days. The contralateral untreated eyes used as controls. Schirmer test, tear break-up time (BUT), rose Bengal and fluorescein staining were performed on days 5, 10, 20, and 30. Central corneal changes were analyzed by in vivo confocal microscopy, and the corneal barrier function was evaluated by measurement of corneal transepithelial electrical resistance on day 5. Whole mount corneas were analyzed by using fluorescence confocal microscopy for the presence of tight-junction (ZO-1, occludin) and adherens-junction (E-cadherin, β-catenin) proteins, actin cytoskeleton, proliferative marker Ki67 and cell apoptosis in the epithelium. Topical application of commercial PG analogs resulted in significant corneal epithelial and stromal defects while no significant changes in aqueous tear production, BUT, rose bengal and fluorescein staining scores on day 5. Commercial PG analogs induced dislocation of ZO-1 and occludin from their normal locus, disorganization of cortical actin cytoskeleton at the superficial layer, and disruption of epithelial barrier function. The eyes treated with 0.02% BAK and latanoprost exhibited significantly reduced Schirmer scores, BUT, and increased fluorescein staining scores on days 10 and 30, respectively. Topical application of commercial PG analogs can quickly impair the corneal epithelium and stroma without tear deficiency. Commercial PG analogs break down the barrier integrity of corneal epithelium, concomitant with the disruption of cell junction and actin cytoskeleton between superficial cells in the corneal epithelium in vivo.

Gap junction intercellular communication (GJIC) plays a critical role in the maintenance of corneal endothelium homeostasis. We determined if benzalkonium chloride (BAK) alters GJIC activity in the rabbit corneal endothelium since it is commonly used as a drug preservative in ocular eyedrop preparations even though it can have cytotoxic effects.Thirty-six adult New Zealand albino rabbits were randomly divided into three groups. BAK at 0.01%, 0.05%, and 0.1% was applied twice daily to one eye of each of the rabbits in one of the three groups for seven days. The contralateral untreated eyes were used as controls. Corneal endothelial morphological features were observed by in vivo confocal microscopy (IVCM). Immunofluorescent staining resolved changes in gap junction integrity and localization. Western blot analysis and RT-PCR evaluated changes in levels of connexin43 (Cx43) and tight junction zonula occludens-1 (ZO-1) gene and protein expression, respectively. Cx43 and ZO-1 physical interaction was detected by immunoprecipitation (IP). Primary rabbit corneal endothelial cells were cultured in Dulbecco's Modified Eagle Medium (DMEM) containing BAK for 24 hours. The scrape-loading dye transfer technique (SLDT) was used to assess GJIC activity.Topical administration of BAK (0.05%, 0.1%) dose dependently disrupted corneal endothelial cell morphology, altered Cx43 and ZO-1 distribution and reduced Cx43 expression. BAK also markedly induced increases in Cx43 phosphorylation status concomitant with decreases in the Cx43-ZO-1 protein-protein interaction. These changes were associated with marked declines in GJIC activity.The dose dependent declines in rabbit corneal endothelial GJIC activity induced by BAK are associated with less Cx43-ZO-1 interaction possibly arising from increases in Cx43 phosphorylation and declines in its protein expression. These novel changes provide additional evidence that BAK containing eyedrop preparations should be used with caution to avoid declines in corneal transparency resulting from losses in GJIC activity and endothelial function.

Although pterostilbene (PTE) has been shown to have potent antitumor activities against various cancer types, the molecular mechanisms of these activities remain unclear. In this study, we investigated the antitumor activity of PTE against human lung adenocarcinoma in vitro and in vivo and explored the role of the Notch1 signaling pathway in this process. PTE treatment resulted in a dose- and time-dependent decrease in the viability of A549 cells. Additionally, PTE exhibited strong antitumor activity, as evidenced not only by a reduced mitochondrial membrane potential (MMP) and a decreased intracellular glutathione content but also by increases in the apoptotic index and the level of reactive oxygen species (ROS). Furthermore, PTE treatment induced the activation of the Notch1 Intracellular Domain (NICD) protein and activated Hes1. DAPT (a gamma secretase inhibitor) and Notch1 siRNA prevented the induction of NICD and Hes1 activation by PTE treatment and sensitized the cells to PTE treatment. The down-regulation of Notch signaling also prevented the activation of pro-survival pathways (most notably the PI3K/Akt pathway) after PTE treatment. In summary, lung adenocarcinoma cells may enhance Notch1 activation as a protective mechanism in response to PTE treatment. Combining a gamma secretase inhibitor with PTE treatment may represent a novel approach for treating lung adenocarcinoma by inhibiting the survival pathways of cancer cells.