Confidential multiple-input multiple-output optical camera communication aided by a two-dimensional pilot.

Optical camera communication (OCC) has attracted increased attention for its inherent security advantage. However, there still exists the risk of eavesdropping on the broadcasting channel of OCC. To achieve confidential communication, we propose the confidentiality-interference dual light-emitting diode (LED) communication (CIDLC) scheme at the transmitter (TX) and elimination of interference (EI) scheme at the receiver (RX). Meanwhile, interference signals refer to the bit shift of confidential signals. Further, we propose the two-dimensional pilot-aided channel estimation (2D-PACE) scheme to enhance the reliability of multiple-input multiple-output (MIMO) OCC. Experiment results validate the effectiveness of our schemes, which guarantee confidentiality while performing well at a 2 m non-line-of-sight (NLOS) distance. Finally, the communication-illumination integration OCC is constructed via the energy equalization coding (EEC) scheme.

R2* mapping and reduced field-of-view diffusion-weighted imaging for preoperative assessment of nonenlarged lymph node metastasis in rectal cancer.

The aim of the current study is to investigate the diagnostic value of R2* mapping versus reduced field-of-view diffusion-weighted imaging (rDWI) of the primary lesion of rectal cancer for preoperative prediction of nonenlarged lymph node metastasis (NLNM). Eighty-one patients with pathologically confirmed rectal cancer underwent preoperative R2* mapping and rDWI sequences before total mesorectal excisions and accompanying regional lymph node dissections. Two radiologists independently performed whole-tumor measurements of R2* and apparent diffusion coefficient (ADC) parameters on primary lesions of rectal cancer. Patients were divided into positive (NLNM+) and negative (NLNM-) groups based on their pathological analysis. The tumor location, maximum diameter of the tumor, and maximum short diameter of the lymph node were assessed. R2* and ADC, pT stage, tumor grade, status of mesorectal fascia, and extramural vascular invasion were also studied for their potential relationships with NLNM using multivariate logistic regression analysis. The NLNM+ group had significantly higher R2* (43.56 ± 8.43 vs. 33.87 ± 9.57, p < 0.001) and lower ADC (1.00 ± 0.13 vs. 1.06 ± 0.22, p = 0.036) than the NLNM- group. R2* and ADC were correlated to lymph node metastasis (r = 0.510, p < 0.001 for R2*; r = -0.235, p = 0.035 for ADC). R2* and ADC showed good and moderate diagnostic abilities in the assessment of NLNM status with corresponding area-under-the-curve values of 0.795 and 0.636. R2* provided a significantly better diagnostic performance compared with ADC for the prediction of NLNM status (z = 1.962, p = 0.0498). The multivariate logistic regression analysis demonstrated that R2* was a compelling factor of lymph node metastasis (odds ratio = 56.485, 95% confidence interval: 5.759-554.013; p = 0.001). R2* mapping had significantly higher diagnostic performance than rDWI from the primary tumor of rectal cancer in the prediction of NLNM status.

Biosynthesis of silver nanoparticles using Burkholderia contaminans ZCC and mechanistic analysis at the proteome level.

The biogenic synthesis of silver nanoparticles (AgNPs) by microorganisms has been a subject of increasing attention. Despite extensive studies on this biosynthetic pathway, the mechanisms underlying the involvement of proteins and enzymes in AgNPs production have not been fully explored. Herein, we reported that Burkholderia contaminans ZCC was able to reduce Ag+ to AgNPs with a diameter of (10±5) nm inside the cell. Exposure of B. contaminans ZCC to Ag+ ions led to significant changes in the functional groups of cellular proteins, with approximately 5.72% of the (C-OH) bonds being converted to (C-C/C-H) (3.61%) and CO (2.11%) bonds, and 4.52% of the CO (carbonyl) bonds being converted to (C-OH) bonds. Furthermore, the presence of Ag+ and AgNPs induced the ability of extracellular electron transfer for ZCC cells via specific membrane proteins, but this did not occur in the absence of Ag+ ions. Proteomic analysis of the proteins and enzymes involved in heavy metal efflux systems, protein secretion system, oxidative phosphorylation, intracellular electron transfer chain, and glutathione metabolism suggests that glutathione S-transferase and ubiquinol-cytochrome c reductase iron-sulfur subunit play importance roles in the biosynthesis of AgNPs. These findings contribute to a deeper understanding of the functions exerted by glutathione S-transferase and ferredoxin-thioredoxin reductase iron-sulfur subunits in the biogenesis of AgNPs, thereby hold immense potential for optimizing biotechnological techniques aimed at enhancing the yield and purity of biosynthetic AgNPs.

AMPA receptor inhibition alleviates inflammatory response and myocardial apoptosis after myocardial infarction by inhibiting TLR4/NF-κB signaling pathway.

Myocardial infarction leads to myocardial inflammation and apoptosis, which are crucial factors leading to heart failure and cardiovascular dysfunction, eventually resulting in death. While the inhibition of AMPA receptors mitigates inflammation and tissue apoptosis, the effectiveness of this inhibition in the pathophysiological processes of myocardial infarction remains unclear. This study investigated the role of AMPA receptor inhibition in myocardial infarction and elucidated the underlying mechanisms. This study established a myocardial infarction model by ligating the left anterior descending branch of the coronary artery in Sprague-Dawley rats. The findings suggested that injecting the AMPA receptor antagonist NBQX into myocardial infarction rats effectively alleviated cardiac inflammation, myocardial necrosis, and apoptosis and improved their cardiac contractile function. Conversely, injecting the AMPA receptor agonist CX546 into infarcted rats exacerbated the symptoms and tissue damage, as reflected by histopathology. This agonist also stimulated the TLR4/NF-κB pathway, further deteriorating cardiac function. Furthermore, the investigations revealed that AMPA receptor inhibition hindered the nuclear translocation of P65, blocking its downstream signaling pathway and attenuating tissue inflammation. In summary, this study affirmed the potential of AMPA receptor inhibition in countering inflammation and tissue apoptosis after myocardial infarction, making it a promising therapeutic target for mitigating myocardial infarction.

Wet Etching of Silicon in Planar Nanochannels.

Silicon (Si) alkaline etching constitutes a fundamental process in the semiconductor industry. Although its etching kinetics on plain substrates have been thoroughly investigated, the kinetics of Si wet etching in nanoconfinements have yet to be fully explored despite its practical importance in three-dimensional (3-D) semiconductor manufacturing. Herein, we report the systematic study of potassium hydroxide (KOH) wet etching kinetics of amorphous silicon (a-Si)-filled two-dimensional (2-D) planar nanochannels. Our findings reveal that the etching rate would increase with the increase in nanochannel height before reaching a plateau, indicating a strong nonlinear confinement effect. Through investigation using etching solutions with different ionic strengths and/or different temperatures, we further find that both electrostatic interactions and the hydration layer inside the nanoconfinement contribute to the confinement-dependent etching kinetics. Our results offer fresh perspectives into the kinetic study of reactions in nanoconfinements and will shed light on the optimization of etching processes in the semiconductor industry.

Expression and significance of pigment epithelium-derived factor and vascular endothelial growth factor in colorectal adenoma and cancer.

BACKGROUND: The incidence and mortality of colorectal cancer (CRC) are among the highest in the world, and its occurrence and development are closely related to tumor neovascularization. When the balance between pigment epithelium-derived factors (PEDF) that inhibit angiogenesis and vascular endothelial growth factors (VEGF) that stimulate angiogenesis is broken, angiogenesis is out of control, resulting in tumor development. Therefore, it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment. AIM: To investigate the expression and significance of PEDF, VEGF, and CD31-stained microvessel density values (CD31-MVD) in normal colorectal mucosa, adenoma, and CRC. METHODS: In this case-control study, we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022. Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy (normal control group), 50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy (adenoma group), and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery (CRC group). An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens, analyze their differences, study the relationship between the two and clinicopathological factors in CRC group, record CD31-MVD in the three groups, and analyze the correlation of PEDF, VEGF, and CD31-MVD in the colorectal adenoma group and the CRC group. The F test or adjusted F test is used to analyze measurement data statistically. Kruskal-Wallis rank sum test was used between groups for ranked data. The chi-square test, adjusted chi-square test, or Fisher's exact test were used to compare the rates between groups. All differences between groups were compared using the Bonferroni method for multiple comparisons. Spearman correlation analysis was used to test the correlation of the data. The test level (α) was 0.05, and a two-sided P< 0.05 was considered statistically significant. RESULTS: The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group, adenoma group, and CRC group (100% vs 78% vs 50%, χ2 = 34.430, P < 0.001; ++~++ vs +~++ vs -~+, H = 94.059, P < 0.001), while VEGF increased gradually (0% vs 68% vs 96%, χ2 = 98.35, P < 0.001; - vs -~+ vs ++~+++, H = 107.734, P < 0.001). In the CRC group, the positive expression rate of PEDF decreased with the increase of differentiation degree, invasion depth, lymph node metastasis, distant metastasis, and TNM stage (χ2 = 20.513, 4.160, 5.128, 6.349, 5.128, P < 0.05); the high expression rate of VEGF was the opposite (χ2 = 10.317, 13.134, 17.643, 21.844, 17.643, P < 0.05). In the colorectal adenoma group, the expression intensity of PEDF correlated negatively with CD31-MVD (r = -0.601, P < 0.001), whereas VEGF was not significantly different (r = 0.258, P = 0.07). In the CRC group, the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF (r = -0.297, P < 0.05; r = -0.548, P < 0.05), while VEGF expression intensity was positively related to CD31-MVD (r = 0.421, P = 0.002). CONCLUSION: It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.

Metabolic disorders in prediabetes: From mechanisms to therapeutic management.

Diabetes, one of the world's top ten diseases, is known for its high mortality and complication rates and low cure rate. Prediabetes precedes the onset of diabetes, during which effective treatment can reduce diabetes risk. Prediabetes risk factors include high-calorie and high-fat diets, sedentary lifestyles, and stress. Consequences may include considerable damage to vital organs, including the retina, liver, and kidneys. Interventions for treating prediabetes include a healthy lifestyle diet and pharmacological treatments. However, while these options are effective in the short term, they may fail due to the difficulty of long-term implementation. Medications may also be used to treat prediabetes. This review examines prediabetic treatments, particularly metformin, glucagon-like peptide-1 receptor agonists, sodium glucose cotransporter 2 inhibitors, vitamin D, and herbal medicines. Given the remarkable impact of prediabetes on the progression of diabetes mellitus, it is crucial to intervene promptly and effectively to regulate prediabetes. However, the current body of research on prediabetes is limited, and there is considerable confusion surrounding clinically relevant medications. This paper aims to provide a comprehensive summary of the pathogenesis of pre-diabetes mellitus and its associated therapeutic drugs. The ultimate goal is to facilitate the clinical utilization of medications and achieve efficient and timely control of diabetes mellitus.

Characterization of cells in blood evoked from periapical tissues in immature teeth with pulp necrosis and their potential for autologous cell therapy in Regenerative Endodontics.

OBJECTIVE: The objectives of this study were to isolate, characterize progenitor cells from blood in the root canals of necrotic immature permanent teeth evoked from periapical tissues and evaluate the applicable potential of these isolated cells in Regenerative Endodontics. DESIGN: Ten necrotic immature permanent teeth from seven patients were included. Evoked bleeding from periapical tissues was induced after chemical instrumentation of the root canals. Cells were isolated from the canal blood and evaluated for cell surface marker expression, multilineage differentiation potential, proliferation ability, and target protein expression. Cell sheets formed from these cells were transferred into human root segments, and then transplanted into nude mice. Histological examination was performed after eight weeks. Data analysis was conducted using one-way ANOVA followed by Tukey's post-hoc comparison, considering p < 0.05 as statistically significant. RESULTS: The isolated cells exhibited characteristics typical of fibroblastic cells with colony-forming efficiency, and displayed Ki67 positivity and robust proliferation. Flow cytometry data demonstrated that at passage 3, these cells were positive for CD73, CD90, CD105, CD146, and negative for CD34 and CD45. Vimentin expression indicated a mesenchymal origin. Under differentiation media specific differentiation media, the cells demonstrated osteogenic, adipogenic, and chondrogenic differentiation potential. Subcutaneous root canals with cell sheets of isolated cells in nude mice showed the formation of pulp-like tissues. CONCLUSIONS: This study confirmed the presence of progenitor cells in root canals following evoked bleeding from periapical tissues of necrotic immature teeth. Isolated cells exhibited similar immunophenotype and regenerative potential with dental mesenchymal stromal cells in regenerative endodontic therapy.

Coordinated optimization of the polymerization and transportation processes to enhance the yield of exopolysaccharide heparosan.

Heparosan as the precursor for heparin biosynthesis has attracted intensive attention while Escherichia coli Nissle 1917 (EcN) has been applied as a chassis for heparosan biosynthesis. Here, after uncovering the pivotal role of KfiB in heparosan biosynthesis, we further demonstrate KfiB is involved in facilitating KpsT to translocate the nascent heparosan polysaccharide chain. As a result, an artificial expression cassette KfiACB was constructed with optimized RBS elements, resulting in 0.77 g/L heparosan in shake flask culture. Moreover, in view of the intracellular accumulation of heparosan, we further investigated the effects of overexpression of the ABC transport system proteins on heparosan biosynthesis. By co-overexpressing KfiACB with KpsTME, the heparosan production in flask cultures was increased to 1.03 g/L with an extracellular concentration of 0.96 g/L. Eventually, the engineered strain EcN/pET-kfiACB3-galU-kfiD-glmM/pCDF-kpsTME produced 12.2 g/L heparosan in 5-L fed-batch cultures while the extracellular heparosan was about 11.2 g/L. The results demonstrate the high-efficiency of the strategy for co-optimizing the polymerization and transportation for heparosan biosynthesis. Moreover, this strategy should be also available for enhancing the production of other polysaccharides.

Construction of 5-Aminolevulinic Acid Microbial Cell Factories through Identification of Novel Synthases and Metabolic Pathway Screens and Transporters.

5-Aminolevulinic acid (5-ALA) plays a pivotal role in the biosynthesis of heme and chlorophyll and has garnered great attention for its agricultural applications. This study explores the multifaceted construction of 5-ALA microbial cell factories. Evolutionary analysis-guided screening identified a novel 5-ALA synthase from Sphingobium amiense as the best synthase. An sRNA library facilitated global gene screening that demonstrated that trpC and ilvA repression enhanced 5-ALA production by 74.3% and 102%, respectively. Subsequently, efflux of 5-ALA by the transporter Gdx increased 5-ALA biosynthesis by 25.7%. To mitigate oxidative toxicity, DNA-binding proteins from starved cells were employed, enhancing cell density and 5-ALA titer by 21.1 and 4.1%, respectively. Combining these strategies resulted in an Escherichia coli strain that produced 5-ALA to 1.51 g·L-1 in shake flask experiments and 6.19 g·L-1 through fed-batch fermentation. This study broadens the repertoire of available 5-ALA synthases and transporters and provides a new platform for optimizing 5-ALA bioproduction.

Chronic nicotine exposure elicits pain hypersensitivity through activation of dopaminergic projections to anterior cingulate cortex.

BACKGROUND: Cigarette smoking is commonly reported among chronic pain patients in the clinic. Although chronic nicotine exposure is directly linked to nociceptive hypersensitivity in rodents, underlying neurobiological mechanisms remain unknown. METHODS: Multi-tetrode recordings in freely moving mice were used to test the activity of dopaminergic projections from the ventral tegmental area (VTA) to pyramidal neurones in the anterior cingulate cortex (ACC) in chronic nicotine-treated mice. The VTA→ACC dopaminergic pathway was inhibited by optogenetic manipulation to detect chronic nicotine-induced allodynia (pain attributable to a stimulus that does not normally provoke pain) assessed by von Frey monofilaments (force units in g). RESULTS: Allodynia developed concurrently with chronic (28-day) nicotine exposure in mice (0.36 g [0.0141] vs 0.05 g [0.0018], P<0.0001). Chronic nicotine activated dopaminergic projections from the VTA to pyramidal neurones in the ACC, and optogenetic inhibition of VTA dopaminergic terminals in the ACC alleviated chronic nicotine-induced allodynia in mice (0.06 g [0.0064] vs 0.28 g [0.0428], P<0.0001). Moreover, optogenetic inhibition of Drd2 dopamine receptor signalling in the ACC attenuated nicotine-induced allodynia (0.07 g [0.0082] vs 0.27 g [0.0211], P<0.0001). CONCLUSIONS: These findings implicate a role of Drd2-mediated dopaminergic VTA→ACC pathway signalling in chronic nicotine-elicited allodynia.

A newly developed deep learning-based system for automatic detection and classification of small bowel lesions during double-balloon enteroscopy examination.

BACKGROUND: Double-balloon enteroscopy (DBE) is a standard method for diagnosing and treating small bowel disease. However, DBE may yield false-negative results due to oversight or inexperience. We aim to develop a computer-aided diagnostic (CAD) system for the automatic detection and classification of small bowel abnormalities in DBE. DESIGN AND METHODS: A total of 5201 images were collected from Renmin Hospital of Wuhan University to construct a detection model for localizing lesions during DBE, and 3021 images were collected to construct a classification model for classifying lesions into four classes, protruding lesion, diverticulum, erosion & ulcer and angioectasia. The performance of the two models was evaluated using 1318 normal images and 915 abnormal images and 65 videos from independent patients and then compared with that of 8 endoscopists. The standard answer was the expert consensus. RESULTS: For the image test set, the detection model achieved a sensitivity of 92% (843/915) and an area under the curve (AUC) of 0.947, and the classification model achieved an accuracy of 86%. For the video test set, the accuracy of the system was significantly better than that of the endoscopists (85% vs. 77 ± 6%, p < 0.01). For the video test set, the proposed system was superior to novices and comparable to experts. CONCLUSIONS: We established a real-time CAD system for detecting and classifying small bowel lesions in DBE with favourable performance. ENDOANGEL-DBE has the potential to help endoscopists, especially novices, in clinical practice and may reduce the miss rate of small bowel lesions.

Exploring the interference mechanisms of surface and aqueous complexes with groundwater arsenate and arsenite adsorption.

Ca2+, Mg2+, and HCO3- are extremely common coexisting ions with arsenic (As) in geogenic As-polluted groundwaters. Although extensive research has improved our knowledge of groundwater As removal techniques and mechanisms, there is still a lack of a definite explanation of the distinct influences of Ca2+ and Mg2+ on As immobilization. Furthermore, the question of whether the occurrence of metal-As aqueous complexes has positive or detrimental effects on As adsorption is still open, which hinders our ability to predict the effectiveness of groundwater As removal. The goal of our present work was to investigate the molecular-level interference mechanisms of Ca2+, Mg2+, and HCO3- on arsenic adsorption with batch/column filtration experiments and spectroscopic techniques. The results showed that the co-presence of Ca2+ and As significantly increased As(V) and As(III) adsorption by 22.1 and 12.2% in batch studies and by 20.1 and 16.7% in column adsorptive filtrations, which could be explained by forming a ternary Ca-As-TiO2 complex. Without the surface complex, Mg2+ only had a slightly positive effect on As removal. Co-existence of Ca2+ and HCO3- prevented the generation this surface complex, which significantly decreased the elimination of As(III). Inversely, the As(V) ternary complex and adsorption were not interfered by HCO3-. Moreover, an aqueous Ca-As(V) complex was detected without surface, which facilitated generation of the surface complex and As(V) adsorption. The results of this work clarified the distinct effects of Ca2+ and Mg2+ and As(V) and As(III) adsorption, which was critical in predicting the As adsorption efficiency in column filtration processes.

Activation of sigma-1 receptor ameliorates sepsis-induced myocardial injury by mediating the Nrf2/HO1 signaling pathway to attenuate mitochondrial oxidative stress.

BACKGROUND: Sepsis is a condition that triggers the release of large amounts of reactive oxygen species and inflammatory factors in the body, leading to myocardial injury and cardiovascular dysfunction - an important contributor to the high mortality rate associated with sepsis. Although it has been demonstrated that the sigma-1 receptor (S1R) is essential for preventing oxidative stress, its effectiveness in treating sepsis is yet unknown. AIM: This study aimed to investigate the role and mechanisms of S1R activation in sepsis-induced myocardial injury. METHODS: A model of sepsis-induced myocardial injury was constructed by performing cecum ligation and puncture(CLP) surgery on rats. Flv or BD1047 were intraperitoneally injected into rats for one consecutive week before performing CLP, and then intraperitoneally injected into the rats again 1 h after the surgery.The effects of Flv and BD1047 were detected by HE staining, immunofluorescence staining, IHC staining, echocardiography measurements,TUNEL, oxidative stress detection, TEM, flow cytometry and western blot. We further validated the mechanism in vitro using neonatal rat cardiomyocites and H9C2 cells. RESULTS: S1R protein level was reduced in the hearts of septic rats, whereas administration of Flv, an S1R activator, ameliorated myocardial injury, mitochondrial oxidative stress, and pathological manifestations of sepsis. On the other hand, administration of the S1R inhibitor BD1047 exacerbated the mitochondrial oxidative stress, and apoptosis, as well as symptoms and pathological manifestations of sepsis. In addition, we found that up-regulation of S1R activated the Nrf2/HO1 signaling pathway and promoted nuclear translocation of Nrf2, which activated downstream proteins to generate antioxidant factors, such as HO1, in turn alleviating oxidative stress and countering myocardial damage. CONCLUSION: By scavenging ROS accumulation and reducing mitochondrial oxidative stress via the Nrf2/HO1 signaling pathway, activation of S1R improves cardiac function, mitigates death of cardiomyocytes, and attenuates sepsis-induced myocardial injury.

Monitoring acoustic vibrations in optical fibers by estimating polarization matrix variation with the integration of coherent optical communication and sensing.

In this paper, we propose a novel architecture called as the Direct-Computation-Sensing Architecture (DCSA) to directly calculates the polarization state changes caused by optical fiber vibrations with training data, offering a more accurate and responsive method than that with adaptive filter-based sensing architectures. We detected the distinct fiber vibration induced by piezoelectric ceramics in an established experimental platform, and recovered a song melody played near the optical fiber buddle from the fiber's polarization changes. We locate the source of the vibration by comparing data from both ends of a bidirectional transmission setup. Lastly, we conducted field tests under conditions involving machine-induced vibrations and natural cable movements.

Ultra-expanded interlayer spacing of vanadium oxide nanowires intercalated with poly(3,4-ethylene dioxythiophene) in organic ammonium ion batteries.

Rechargeable batteries employing ammonium (NH4+) ions have attracted widespread interest owing to the abundant resources, eco-friendliness, and sustainability of NH4+ ions. Herein, an organic-inorganic hybrid is applied to organic NH4+ ion batteries. A poly (3,4-ethylene dioxythiophene) (PEDOT)-intercalated vanadium oxide nanowire (noted as VO-P-x) is applied for organic NH4+ ion storage. VO-P-x with the optimal content of PEDOT showed an interlayer spacing (d-spacing) expanded to 1.82 nm, exhibiting an ultrahigh initial coulombic efficiency of 91% and a reversible capacity of 163 mA h g-1. A significant improvement in NH4+ ion storage was achieved due to the large interlayer spacing and conductive polymer PEDOT. Combining ex situ X-ray photoelectron spectroscopy (XPS) and multi-sweep cyclic voltammetry tests, the NH4+ ion storage mechanism of VO-P-x was clearly revealed. This study provides a new strategy for designing high-performance organic ammonium batteries.

Association of sex-specific abdominal adipose tissue with WHO/ISUP grade in clear cell renal cell carcinoma.

OBJECTIVES: To explore the association between computed tomography (CT)-measured sex-specific abdominal adipose tissue and the pathological grade of clear cell renal cell carcinoma (ccRCC). METHODS: This retrospective study comprised 560 patients (394 males and 166 females) with pathologically proven ccRCC (467 low- and 93 high-grade). Abdominal CT images were used to assess the adipose tissue in the subcutaneous, visceral, and intermuscular regions. Subcutaneous fat index (SFI), visceral fat index (VFI), intermuscular fat index (IFI), total fat index (TFI), and relative visceral adipose tissue (rVAT) were calculated. Univariate and multivariate logistic regression analyses were performed according to sex to identify the associations between fat-related parameters and pathological grade. RESULTS: IFI was significantly higher in high-grade ccRCC patients than in low-grade patients for both men and women. For male patients with high-grade tumors, the SFI, VFI, TFI, and rVAT were significantly lower, but not for female patients. In both univariate and multivariate studies, the IFI continued to be a reliable and independent predictor of high-grade ccRCC, regardless of sex. CONCLUSIONS: Intermuscular fat index proved to be a valuable biomarker for the pathological grade of ccRCC and could be used as a reliable independent predictor of high-grade ccRCC for both males and females. CRITICAL RELEVANCE STATEMENT: Sex-specific fat adipose tissue can be used as a new biomarker to provide a new dimension for renal tumor-related research and may provide new perspectives for personalized tumor management decision-making approaches. KEY POINTS: • There are sex differences in distribution of subcutaneous fat and visceral fat. • The SFI, VFI, TFI, and rVAT were significantly lower in high-grade ccRCC male patients, but not for female patients. • Intermuscular fat index can be used as a reliable independent predictor of high-grade ccRCC for both males and females.

Serinc2 deficiency exacerbates sepsis-induced cardiomyopathy by enhancing necroptosis and apoptosis.

In critical care medicine, sepsis is a potentially fatal syndrome characterized by multi-organ dysfunction and eventual failure. Sepsis-induced cardiomyopathy (SIC) is characterized by decreased venstricular contractility. Serine incorporator 2 (Serinc2) is a protein involved in phosphatidylserine biosynthesis and membrane incorporation. It may also be a protective factor in septic lung injury. However, it is unknown whether Serinc2 influences SIC onset or progression. In the present study, we found that Serinc2 was downregulated in the cardiomyocytes of cecal ligation and puncture (CLP)-induced SIC and in neonatal rat cardiomyocytes (NRCMs) exposed to lipopolysaccharides (LPS). Serinc2 knockout (KO) exacerbated sepsis-induced myocardial inflammation, necroptosis, apoptosis, myocardial damage, and contractility impairment. Furthermore, the lack of Serinc2 in cardiomyocytes aggravated LPS-induced cardiomyopathic inflammation, necroptosis, and apoptosis. An adenovirus overexpressing Serinc2 inhibited the inflammatory response and favored cardiomyocyte survival. A mechanistic analysis revealed that Serinc2 deficiency exacerbated LPS-induced cardiac dysfunction by inhibiting the protein kinase B (Akt)/glycogen synthase kinase 3 beta (GSK-3ß) signaling pathway that regulates necrotic complex formation and apoptotic pathways in cardiomyopathy. The findings of the present work demonstrated that Serinc2 plays an essential role in SIC and is, therefore, promising as a prophylactic and therapeutic target for this condition.

PET imaging with [68Ga]-labeled TGFß-targeting peptide in a mouse PANC-1 tumor model.

Purpose: Transforming growth factor ß (TGFß) is upregulated in many types of tumors and plays important roles in tumor microenvironment construction, immune escape, invasion, and metastasis. The therapeutic effect of antibodies and nuclide-conjugated drugs targeting TGFß has not been ideal. Targeting TGFß with small-molecule or peptide carriers labeled with diagnostic/therapeutic nuclides is a new development direction. This study aimed to explore and confirm the imaging diagnostic efficiency of TGFß-targeting peptide P144 coupled with [68Ga] in a PANC-1 tumor model. Procedures: TGFß-targeting inhibitory peptide P144 with stable activity was prepared through peptide synthesis and screening, and P144 was coupled with biological chelator DOTA and labeled with radionuclide [68Ga] to achieve a stable TGFß-targeting tracer [68Ga]Ga-P144. This tracer was first used for positron emission tomography (PET) molecular imaging study of pancreatic cancer in a mouse PANC-1 tumor model. Results: [68Ga]Ga-P144 had a high targeted uptake and relatively long uptake retention time in tumors and lower uptakes in non-target organs and backgrounds. Target pre-blocking experiment with the cold drug P144-DOTA demonstrated that the radioactive uptake with [68Ga]Ga-P144 PET in vivo, especially in tumor tissue, had a high TGFß-targeting specificity. [68Ga]Ga-P144 PET had ideal imaging efficiency in PANC-1 tumor-bearing mice, with high specificity in vivo and good tumor-targeting effect. Conclusion: [68Ga]Ga-P144 has relatively high specificity and tumor-targeted uptake and may be developed as a promising diagnostic tool for TGFß-positive malignancies.

Advances in Research on Type 2 Diabetes Mellitus Targets and Therapeutic Agents.

Diabetes mellitus is a chronic multifaceted disease with multiple potential complications, the treatment of which can only delay and prolong the terminal stage of the disease, i.e., type 2 diabetes mellitus (T2DM). The World Health Organization predicts that diabetes will be the seventh leading cause of death by 2030. Although many antidiabetic medicines have been successfully developed in recent years, such as GLP-1 receptor agonists and SGLT-2 inhibitors, single-target drugs are gradually failing to meet the therapeutic requirements owing to the individual variability, diversity of pathogenesis, and organismal resistance. Therefore, there remains a need to investigate the pathogenesis of T2DM in more depth, identify multiple therapeutic targets, and provide improved glycemic control solutions. This review presents an overview of the mechanisms of action and the development of the latest therapeutic agents targeting T2DM in recent years. It also discusses emerging target-based therapies and new potential therapeutic targets that have emerged within the last three years. The aim of our review is to provide a theoretical basis for further advancement in targeted therapies for T2DM.