Synergistic peptide combinations designed to suppress SARS-CoV-2.

The SARS-CoV-2, responsible for the COVID-19 pandemic, poses a significant threat to global healthcare. Peptide and peptide-based inhibitors, known for their safety, efficacy, and selectivity, have recently emerged as promising candidates for treating late-developing viral infections. In this study, three peptides were selected to target different stages of viral invasion, specifically ACE2 and S protein binding, as well as membrane fusion. The objective was to assess their ability to impede the entry of the SARS-CoV-2 Spike pseudotyped virus. Our findings revealed that a combination of these three peptides demonstrated enhanced antiviral effects. This outcome substantiates the feasibility of developing effective peptide combinations to combat diseases related to SARS-CoV-2. Moreover, the three-peptide combinations, designed to target multiple aspects of SARS-CoV-2 viral entry, exhibited heightened viral inhibition and broad-spectrum antiviral properties.

Palmitoylation of KSHV pORF55 is required for Golgi localization and efficient progeny virion production.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus etiologically associated with multiple malignancies. Both latency and sporadic lytic reactivation contribute to KSHV-associated malignancies, however, the specific roles of many KSHV lytic gene products in KSHV replication remain elusive. In this study, we report that ablation of ORF55, a late gene encoding a tegument protein, does not impact KSHV lytic reactivation but significantly reduces the production of progeny virions. We found that cysteine 10 and 11 (C10 and C11) of pORF55 are palmitoylated, and the palmytoilation is essential for its Golgi localization and secondary envelope formation. Palmitoylation-defective pORF55 mutants are unstable and undergo proteasomal degradation. Notably, introduction of a putative Golgi localization sequence to these palmitoylation-defective pORF55 mutants restores Golgi localization and fully reinstates KSHV progeny virion production. Together, our study provides new insight into the critical role of pORF55 palmitoylation in KSHV progeny virion production and offers potential therapeutic targets for the treatment of related malignancies.

Assessment of Cerebral White Matter Involvement in Amyotrophic Lateral Sclerosis Patients With Disease Progression and Cognitive Impairment by Fixel-Based Analysis and Neurite Orientation Dispersion and Density Imaging.

BACKGROUND: Previous studies using emerging diffusion MRI techniques have revealed damage to the white matter (WM) microstructure in amyotrophic lateral sclerosis (ALS), particularly the influence of crossed fibers, but there is a lack of subgroup analyses. PURPOSE: To detect WM microstructural changes in ALS patients using fixel-based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI) MRI. STUDY TYPE: Prospective. POPULATION: Thirty-six ALS patients (aged 60.50 ± 9.5 years) and 25 healthy controls (HCs) (aged 58.90 ± 8.1 years). FIELD STRENGTH/SEQUENCE: 3 T; NODDI and FBA (b-values = 0, 1000, and 2500 seconds/mm2 ). ASSESSMENT: Subgroups were performed according to progression rate and cognition, including fast and slow progression (FP/SP), ALS with and without cognitive impairment (ALS-ci/ALS-nci). Fiber density (FD), fiber-bundle cross-section (FC), combined fiber density and cross-section (FDC), neurite density index (NDI), orientation dispersion index (ODI), isotropic volume fraction (ISO), and fractional anisotropy (FA) were calculated and their correlation with clinical variables examined. STATISTICAL TESTING: Chi-square test, Mann-Whitney U test, two-sample t test, partial correlation analysis, and false discovery rate (FDR) corrected. A P-value <0.05 was considered significant. RESULTS: ALS patients had lower FD and FDC values predominantly in the corticospinal tract (CST) and corpus callosum (CC) regions, as well as lower NDI value in the CC, radial crown, and internal capsule compared to HCs. Subgroup analysis based on progression rate and cognitive function showed significant differences in FBA results. The FC in the right CST region was significantly lower in the FP than SP, and the FD in the CC region was significantly lower in the ALS-ci than ALS-nci. Furthermore, a negative correlation was found between the mean FC value and the rate of progression in ALS patients (r = -0.408). DATA CONCLUSION: FBA is a powerful tool for detecting complex cerebral WM microstructural damage for evaluating ALS cognition and disease progression.

Neovascular Age-Related Macular Degeneration in a Predominantly Black Population.

BACKGROUND AND OBJECTIVE: We intend to study the characteristics and outcomes of an understudied patient population with neovascular age-related macular degeneration (nAMD). PATIENTS AND METHODS: This retrospective study evaluated presenting features and outcomes in a predominantly Black patient population with nAMD. A multivariate regression explored baseline characteristics predictive of 1-year vision. RESULTS: Sixty-three eyes were included. The median (interquartile range) baseline vision was 20/300 (20/80 to counting fingers). Patients' baseline optical coherence tomography findings showed a mean central subfield thickness of 336 µm; 80% (n = 35) and 41% (n = 18) had fluid and central scarring, respectively. The primary predictor for vision at year-one was baseline vision (P = 0.03, 95% CI: 0.04 to 0.91). All of those who gained ≥ 3 lines of vision lacked central scarring at baseline. CONCLUSION: Further studies are needed to investigate how to improve earlier detection and treatment of nAMD in this patient population. [Ophthalmic Surg Lasers Imaging Retina 2023;54:580-584.].

The Use of Diffusion Tensor Imaging in the Identification of Acute Rejection and Chronic Allograft Nephropathy After Renal Transplantation.

BACKGROUND: Identifying the cause of renal allograft dysfunction is important for the clinical management of kidney transplant recipients. PURPOSE: To evaluate the diagnostic efficiency of diffusion tensor imaging (DTI) for identifying allografts with acute rejection (AR) and chronic allograft nephropathy (CAN). STUDY TYPE: Prospective. SUBJECTS: Seventy-seven renal transplant patients (aged 42.5 ± 9.5 years), including 29 patients with well-functioning stable allografts (Control group), 25 patients diagnosed with acute rejection (AR group), and 23 patients diagnosed with chronic allograft nephropathy (CAN group). FIELD STRENGTH/SEQUENCE: 1.5 T/T2-weighted imaging and DTI. ASSESSMENT: The serum creatinine, proteinuria, pathologic results, and fractional anisotropy (FA) values were obtained and compared among the three groups. STATISTICAL TEST: One-way analysis of variance; correlation analysis; independent-sample t-test; intraclass correlation coefficients and receiver operating characteristic curves. Statistical significance was set to a P-value <0.05. RESULTS: The AR and CAN groups presented with significantly elevated serum creatinine as compared with the Control group (191.8 ± 181.0 and 163.1 ± 115.8 µmol/L vs. 82.3 ± 20.9 µmol/L). FA decreased in AR group (cortical/medullary: 0.13 ± 0.02/0.31 ± 0.07) and CAN group (cortical/medullary: 0.11 ± 0.02/0.27 ± 0.06), compared with the Control group (cortical/medullary: 0.15 ± 0.02/0.35 ± 0.05). Cortical FA in the AR group was higher than in the CAN group. The area under the curve (AUC) for identifying AR from normal allografts was 0.756 and 0.744 by cortical FA and medullary FA, respectively. The AUC of cortical FA and medullary FA for differentiating CAN from normal allografts was 0.907 and 0.830, respectively. The AUC of cortical FA and medullary FA for distinguishing AR and CAN from normal allografts was 0.828 and 0.785, respectively. Cortical FA was able to distinguish between AR and CAN with an AUC of 0.728. DATA CONCLUSION: DTI was able to detect patients with dysfunctional allografts. Cortical FA can further distinguish between AR and CAN. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Nonmetallic SERS-based biosensor for ultrasensitive and reproducible immunoassay of ferritin mediated by magnetic molybdenum disulfide nanoflowers and black phosphorus nanosheets.

To improve the curability of cancer patients, it is essential to propose an early diagnosis technology with ultra-high sensitivity and reliable biocompatibility. Herein, a sophisticated nonmetallic SERS-based immunosensor, comprised by a MoS2 @Fe3O4 nanoflower-based immunoprobe with magnetism and a black phosphorus (BP) nanosheet-based immunosubstrate, was proposed for the specific in-situ monitoring of ferritin (FER). The sandwich immunosensor was endowed with an excellent SERS performance mainly ascribed to a synergistic chemical enhancement as well as an additional electrostatic adsorption effect, achieving a limit of detection down to 7.3 × 10-5 µg/mL. Particularly, all the Raman label, target FER, and anti-FER could be completely degraded within 70 min under visible light irradiation owing to the favorable photocatalytic activities of MoS2 and BP which could be then effectively separated and collected with the assistance of an external magnet. Such a recyclable nonmetallic immunosensor holds great potential and practicality in the clinical screening of cancer.

Prognostic signatures of sphingolipids: Understanding the immune landscape and predictive role in immunotherapy response and outcomes of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a complex disease with a poor outlook for patients in advanced stages. Immune cells play an important role in the progression of HCC. The metabolism of sphingolipids functions in both tumor growth and immune infiltration. However, little research has focused on using sphingolipid factors to predict HCC prognosis. This study aimed to identify the key sphingolipids genes (SPGs) in HCC and develop a reliable prognostic model based on these genes. Methods: The TCGA, GEO, and ICGC datasets were grouped using SPGs obtained from the InnateDB portal. A prognostic gene signature was created by applying LASSO-Cox analysis and evaluating it with Cox regression. The validity of the signature was verified using ICGC and GEO datasets. The tumor microenvironment (TME) was examined using ESTIMATE and CIBERSORT, and potential therapeutic targets were identified through machine learning. Single-cell sequencing was used to examine the distribution of signature genes in cells within the TME. Cell viability and migration were tested to confirm the role of the key SPGs. Results: We identified 28 SPGs that have an impact on survival. Using clinicopathological features and 6 genes, we developed a nomogram for HCC. The high- and low-risk groups were found to have distinct immune characteristics and response to drugs. Unlike CD8 T cells, M0 and M2 macrophages were found to be highly infiltrated in the TME of the high-risk subgroup. High levels of SPGs were found to be a good indicator of response to immunotherapy. In cell function experiments, SMPD2 and CSTA were found to enhance survival and migration of Huh7 cells, while silencing these genes increased the sensitivity of Huh7 cells to lapatinib. Conclusion: The study presents a six-gene signature and a nomogram that can aid clinicians in choosing personalized treatments for HCC patients. Furthermore, it uncovers the connection between sphingolipid-related genes and the immune microenvironment, offering a novel approach for immunotherapy. By focusing on crucial sphingolipid genes like SMPD2 and CSTA, the efficacy of anti-tumor therapy can be increased in HCC cells.

Quantitative detection of purine from food products with different water activities using needle-based surface-enhanced Raman scattering sensors.

Typically, for accurate quantitative tests of molecules, considering the actual solute concentration in the environment with different water activities (Aws) is essential. Accordingly, for effective detection of food substances, this paper proposes a non-destructive pluggable sensor to capture and monitor four free purines based on surface-enhanced Raman scattering characteristics such as sensitivity, uniformity, repeatability, and stability. In particular, we investigate the impact of Aw on the evaluation of purine detection and its deviation corrections. Furthermore, the recoveries of purine from three food products, including fish (Aw: 0.99), ham (Aw: 0.91), and bacon (Aw: 0.73), are subsequently explored to validate the reliability of the proposed method. The results indicate that the proposed non-destructive pluggable sensor performs better when the Aw is considered. Therefore, this strategy for achieving more reliable quantitative detection by rectifying deviations based on the Aw can significantly help monitor food quality.

A non-metallic SERS-based immunoassay founded by light-harvesting effect and strengthened chemical enhancement.

Owing to its promising biocompatibility and reliable sensitivity, semiconductor-guided surface-enhanced Raman scattering (SERS) technology has aroused widespread concern in clinical immunoassays. Herein, the well-improved light capture capability of MoS2 with a novel three-dimensional (3D) flower-like morphology was combined with the synergistic chemical enhancement from a MoS2@red phosphorus (RP) hybrid system, facilitating an attractive non-metallic SERS-based detection of ferritin in serum. Owing to the remarkable enhancement factors of both the immunoprobe and immunosubstrate, which were comparable to noble metal, an extremely low limit detection of 11.5 pg mL-1 was achieved in the absence of fluorescence interference. In particular, the trace ferritin in the clinical serum sample was successfully monitored, demonstrating superior sensitivity to the traditional chemiluminescent method. Overall, this study convincingly revealed the feasibility and reliability of SERS-based immunoassays induced by biocompatible semiconductors, which has opened a new way to implement the detection and tracking of biomarkers in the human body.

An Interpretable Deep Embedding Model for Few and Imbalanced Biomedical Data.

In healthcare, training examples are usually hard to obtain (e.g., cases of a rare disease), or the cost of labelling data is high. With a large number of features ( p) be measured in a relatively small number of samples ( N), the "big p, small N" problem is an important subject in healthcare studies, especially on the genomic data. Another major challenge of effectively analyzing medical data is the skewed class distribution caused by the imbalance between different class labels. In addition, feature importance and interpretability play a crucial role in the success of solving medical problems. Therefore, in this paper, we present an interpretable deep embedding model (IDEM) to classify new data having seen only a few training examples with highly skewed class distribution. IDEM model consists of a feature attention layer to learn the informative features, a feature embedding layer to directly deal with both numerical and categorical features, a siamese network with contrastive loss to compare the similarity between learned embeddings of two input samples. Experiments on both synthetic data and real-world medical data demonstrate that our IDEM model has better generalization power than conventional approaches with few and imbalanced training medical samples, and it is able to identify which features contribute to the classifier in distinguishing case and control.

Brush-like gold nanowires-anchored g-C3N4 nanosheets with tunable geometry for ultrasensitive and regenerative SERS detection of gaseous molecules.

Strapping plasmonic substrate with a reliable ability to anchor molecules and achieve reproducible result provides trustworthy opportunities for flourishing surface-enhanced Raman scattering (SERS) technique. Herein, a facile controllable in-situ anisotropic growth strategy was exploited to anchor gold nanowires (Au NWs) onto two-dimensional g-C3N4 nanosheets (g-C3N4/Au NWs), facilitating a sensitive and recyclable SERS sensor for gaseous analytes. Benefiting from the attractive enrichment effect of the brush-like surface formed by numerous small Au NWs as well as their rich nanotips-mediated enhancement capability, the hybrid substrate showed an outstanding performance in SERS-based detection of trace 4-Aminothiophenol (4-ATP) molecules, demonstrating a monitoring limitation down to 10-8 M even in atmosphere. Satisfyingly, under visible light illumination, the efficient green photocatalytic ability derived from the g-C3N4 supporting matrix rendered reusable capability for the substrate, whose SERS signal was kept at a persistent high level throughout 6 cycles. Attributed to the narrow line width of SERS spectrum, the 4-ATP assay under the interference of 2-naphthalenethiol (2-NAT) was acquired in gas phase and the dependable recovery rates from 85.4 to 93.9% were confirmed as well. Thanks to the intriguing features including excellent sensitivity and recyclability, the g-C3N4/Au NWs substrate proposed here will pave the way toward the potential application of SERS technique in multiplexed gaseous detection.

Multifunctional SERS chip mediated by black phosphorus@gold-silver nanocomposites inserted in bilayer membrane for in-situ detection and degradation of hazardous materials.

Self-cleaning surface-enhanced Raman scattering (SERS) substrates dependent on versatile two-dimensional semiconductors offer an efficient channel for the sensitive monitoring and timely degradation of hazardous molecules. Herein, a kind of sophisticated SERS-active nanocomposites was developed by incorporating Au-Ag nanoparticles onto black phosphorus (BP) nanosheets via photo-induced self-reduction. Combining the substantial electromagnetic "hot spots" triggered by bimetallic plasma coupling effect and the efficient charge transfer from BP to probe molecules, the proposed nanocomposites featured attractive SERS enhancement, facilitating a limit of detection down to 4.5 × 10-10 M. Attributed to the remarkable restriction of electron-hole recombination stemming from "Schottky contact", the photocatalytic activity of BP was prominently boosted, demonstrating a complete degradation time as short as 65 min. Furthermore, the disgusting instability of BP was considerably hindered by inserting the nanocomposites into various bilayer matrices with diverse hardness and viscosity inspired by cling film principle. Moreover, a significantly elevated collection rate high to 93.1% for in-situ detection was also achieved by the as-manufactured flexible SERS chips based on tape. This study illustrates a clear perspective for the development of versatile BP-based SERS chips which might facilitate sensitive analysis and treatment of perilous contaminants in complicated real-life scenarios.

[Efficacy Evaluation of Three Endoscopic Therapies of Isolated Gastric Varices with Modified Tissue Adhesive].

Objective: To evaluate the efficacy of three endoscopic therapies of isolated gastric varices (IGV) with modified tissue adhesive. Methods: A retrospective analysis was conducted with the clinical data of 73 IGV patients who were treated between January 2008 and December 2019 at Beijing Ditan Hospital. Patient clinical data on age, sex, etiology, biochemistry findings, Child-Pugh classification, the type of spontaneous shunt, preoperative bleeding history, and the presence or absence of liver cancer were collected. The three therapies evaluated were endoscopic intravenous injection of tissue glue combined with lauromacrogol, endoscopic clip-assisted intravenous injection of tissue glue combined with lauromacrogol, and endoscopic clip and LOOP-assisted intravenous injection of tissue glue combined with lauromacrogol. Their respective clinical treatment outcomes, including ectopic embolism rate, survival rate, rebleeding rate, amount of lauromacrogol and tissue glue used, the number of endoscopic clips used, and the number of times of the procedure the patient underwent, were evaluated. Results: In the patient baseline data, Child-Pugh grade, preoperative thrombus formation, and the presence or absence of liver cancer, showed significant difference between the three therapies ( P<0.05). There was no significant difference in the rates of ectopic embolism among the three methods ( P>0.05), but no ectopic embolism occurred after endoscopic clip-assisted intravenous injection of tissue glue combined with lauromacrogol, or after endoscopic clip and LOOP-assisted intravenous injection of tissue glue combined with lauromacrogol. There was no significant difference in the survival rate, the rebleeding rate, amount of lauromacrogol and tissue glue used for the three therapies, but there was significant difference in the number of endoscopic clips used and the number of times the procedure was conducted within one year ( P<0.05). Conclusion: The two endoscopic therapies of intravenous injection of modified tissue glue, one assisted by clip and the other assisted by clip and LOOP, can help reduce the number of procedures IGV patients undergo within one year.

Coupling reconstruction of atmospheric hydrological profile and dry-up risk prediction in a typical lake basin in arid area of China.

Arid area is very sensitive to global warming and are extremely vulnerable to climate change. Moreover, the water resources system in the arid area is fragile and will undergo tremendous changes with climate change. Therefore, the interaction of climate and hydrology in arid area has an important impact on the formation of regional microclimate and hydrological changes. Daihai Lake is a typical closed inland lake in arid area of China, and a key area for ecological protection in North China. In this paper, WRF-Hydro model is used to simulate the climate hydrological coupling situation of Daihai Basin from 1980 to 2020, and the coupling results are verified and calibrated by meteorological statistics, runoff calculation and remote sensing analysis. Based on the synopsis of climate and hydrology in the past 40 years, the causes and future trends of the hydrological elements in Daihai Basin are analyzed. Through the analysis, it is found that the interannual variation of precipitation in Daihai Basin is sharp, with 401.75 mm as the average from 1980 to 1994; and drastic fluctuations from 1995 to 2011, with a difference of nearly 400 mm between the interannual maximum and minimum; From 2012 to 2020, the fluctuation is small. Although the interannual variation of evaporation fluctuated, it showed an upward trend with a slope of 8.855 mm/year. The annual average temperature showed an obvious upward trend with a slope of 0.040 °C/year. From 1980 to 2020, the inflow of Daihai Lake shows a downward trend; Since 2013, the runoff into the lake has tended to be flat. Climate change and human activities are the decisive factors leading to the change of water quantity in Daihai, among which human activities play a greater role. Cultivated land irrigation and industrial water use are highly correlated with the lake discharge, and these two factors have a great influence on the lake discharge. If the current agricultural and industrial water consumption does not increase, Daihai still has a lifespan of nearly 120 years. If human activities do not change and any protective measures are not taken in time, under the background of global climate change, the flow of the Daihai Lake into the lake will be reduced to zero in 2025, and the Daihai Lake will completely dry up in 2031-2033. The study of climate hydrological coupling of long time series in Daihai Basin can not only make up for the lack of runoff data, but also provide the basis for water resources management, disaster prevention and mitigation.

Animal Models of Femur Head Necrosis for Tissue Engineering and Biomaterials Research.

Femur head necrosis, also known as osteonecrosis of the femoral head (ONFH), is a widespread disabling pathology mostly affecting young and middle-aged population and one of the major causes of total hip arthroplasty in the elderly. Currently, there are limited number of different clinical or medication options for the treatment or the reversal of progressive ONFH, but their clinical outcomes are neither satisfactory nor consistent. In pursuit of more reliable therapeutic strategies for ONFH, including recently emerged tissue engineering and biomaterials approaches, in vivo animal models are extremely important for therapeutic efficacy evaluation and mechanistic exploration. Based on the better understanding of pathogenesis of ONFH, animal modeling method has evolved into three major routes, including steroid-, alcohol-, and injury/trauma-induced osteonecrosis, respectively. There is no consensus yet on a standardized ONFH animal model for tissue engineering and biomaterial research; therefore, appropriate animal modeling method should be carefully selected depending on research purposes and scientific hypotheses. In this work, mainstream types of ONFH animal model and their modeling techniques are summarized, showing both merits and demerits for each. In addition, current studies and experimental techniques of evaluating therapeutic efficacy on the treatment of ONFH using animal models are also summarized, along with discussions on future directions related to tissue engineering and biomaterial research. Impact statement Exploration of tissue engineering and biomaterial-based therapeutic strategy for the treatment of femur head necrosis is important since there are limited options available with satisfactory clinical outcomes. To promote the translation of these technologies from benchwork to bedside, animal model should be carefully selected to provide reliable results and clinical outcome prediction. Therefore, osteonecrosis of the femoral head animal modeling methods as well as associated tissue engineering and biomaterial research are overviewed and discussed in this work, as an attempt to provide guidance for model selection and optimization in tissue engineering and biomaterial translational studies.

Reusable dual-functional SERS sensor based on gold nanoflowers-modified red phosphorus nanoplates for ultrasensitive immunoassay and degradation of CA19-9.

It is tremendously desirable for the timely and effective detection of cancer to facilitate the ultra-highly sensitive monitoring of tumor marker in clinical serum sample. In this study, an electromagnetic and chemical synergistically enabled recyclable immunoassay based on surface-enhanced Raman scattering (SERS) was proposed by realizing the anisotropic growth of sea-urchin-like gold nanoflowers (Au NFs) on two-dimensional red phosphorus (RP) nanoplates. Besides the achieved enhancement factor as high as 2.24 × 106, it was found that the photocatalytic and SERS activities were kept at a high level for the hybrid substrate of RP/Au NFs throughout 7 cycles of immunoassay. In combination with a non-metallic immunoprobe, the limit of detection was drove to 7.41 × 10-5 IU·mL-1 for cancer antigen 19-9. The comparative experiments of nonspecific monitoring verified the promising selectivity of this strategy. Considering the intriguing features of high sensitivity, recyclability, and specificity, the proposed multifunctional RP/Au NFs exhibited its superior role in the early detection of cancer and can be adapted for point-of-care diagnosis.

The complete chloroplast genome of Vicia cracca L.

Vicia cracca L. is a widespread perennial herb in the Northern Hemisphere. It has purple flowers and leave tendrils for climbing on neighboring vegetation. For knowing the chloroplast genome, a sample's genomic was extracted, sequenced, assembled and annotated. The chloroplast genome of this plant is a circular form of 126,272bp in length with IR loss. After annotation, a total of 108 genes were predicted, of which, 75 encode proteins, 3 rRNA, 30 tRNA. The evolutionary history, inferred using Maximum Likelihood method, indicates that V. cracca was grouped within Vicia in Fabaceae. The complete cp genome will be helpful for further studies on molecular biology, evolution, population genetics, taxonomy or resources protection.