Clinical application of SARS-CoV-2 antibody detection and monoclonal antibody therapies against COVID-19.

The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodies (mAbs) in the treatment of coronavirus infectious disease 2019 (COVID-19). The dynamic changes of SARS-CoV-2 specific antibodies during COVID-19 were studied. Immunoglobulin M (IgM) appeared earlier and lasted for a short time, while immunoglobulin G (IgG) appeared later and lasted longer. IgM tests can be used for early diagnosis of COVID-19, and IgG tests can be used for late diagnosis of COVID-19 and identification of asymptomatic infected persons. The combination of antibody testing and nucleic acid testing, which complement each other, can improve the diagnosis rate of COVID-19. Monoclonal anti-SARS-CoV-2 specific antibodies can be used to treat hospitalized severe and critically ill patients and non-hospitalized mild to moderate COVID-19 patients. COVID-19 convalescent plasma, highly concentrated immunoglobulin, and anti-SARS-CoV-2 specific mAbs are examples of anti-SARS-CoV-2 antibody products. Due to the continuous emergence of mutated strains of the novel coronavirus, especially omicron, its immune escape ability and infectivity are enhanced, making the effects of authorized products reduced or invalid. Therefore, the optimal application of anti-SARS-CoV-2 antibody products (especially anti-SARS-CoV-2 specific mAbs) is more effective in the treatment of COVID-19 and more conducive to patient recovery.

Lactic acid bacteria biofilms and their antimicrobial potential against pathogenic microorganisms.

The continuous growth of pathogenic microorganisms and associated biofilms poses severe public health challenges, particularly in food and clinical environments. However, these difficulties have enabled scientists to develop novel and safe methods for combating pathogens. The use of biofilms produced by lactic acid bacteria (LAB) against pathogenic bacteria has recently gained popularity. This review provides an in-depth look at LAB biofilms, their distribution, and mechanisms of action against pathogenic bacteria. More importantly, the bioactive substances produced by LAB-forming biofilm may be active against undesirable microorganisms and their products, which is of great interest in improving human health. Therefore, this review implies that a combination of LAB biofilms and other LAB products like bacteriocins could provide viable alternatives to traditional methods of combating pathogenic microorganisms and their biofilms.

Advanced Nitric Oxide Generating Nanomedicine for Therapeutic Applications.

Nitric oxide (NO), a gaseous transmitter extensively present in the human body, regulates vascular relaxation, immune response, inflammation, neurotransmission, and other crucial functions. Nitrite donors have been used clinically to treat angina, heart failure, pulmonary hypertension, and erectile dysfunction. Based on NO's vast biological functions, it further can treat tumors, bacteria/biofilms and other infections, wound healing, eye diseases, and osteoporosis. However, delivering NO is challenging due to uncontrolled blood circulation release and a half-life of under five seconds. With advanced biotechnology and the development of nanomedicine, NO donors packaged with multifunctional nanocarriers by physically embedding or chemically conjugating have been reported to show improved therapeutic efficacy and reduced side effects. Herein, we review and discuss recent applications of NO nanomedicines, their therapeutic mechanisms, and the challenges of NO nanomedicines for future scientific studies and clinical applications. As NO enables the inhibition of the replication of DNA and RNA in infectious microbes, including COVID-19 coronaviruses and malaria parasites, we highlight the potential of NO nanomedicines for antipandemic efforts. This review aims to provide deep insights and practical hints into design strategies and applications of NO nanomedicines.

Disruption of the amino acid transporter CsAAP2 inhibits auxin-mediated root development in cucumber.

Amino acid transporters are the principal mediators of organic nitrogen distribution within plants and are essential for plant growth and development. Despite this importance, relatively few amino acid transporter genes have been explored and elucidated in cucumber (Cucumis sativus). Here, a total of 86 amino acid transporter genes were identified in the cucumber genome. We further identified Amino Acid Permease (AAP) subfamily members that exhibited distinct expression patterns in different tissues. We found that the CsAAP2 as a candidate gene encoding a functional amino acid transporter is highly expressed in cucumber root vascular cells. CsAAP2 knockout lines exhibited arrested development of root meristem, which then caused the delayed initiation of lateral root and the inhibition of root elongation. What is more, the shoot growth of aap2 mutants was strongly retarded due to defects in cucumber root development. Moreover, aap2 mutants exhibited higher concentrations of amino acids and lignin in roots. We found that the mutant roots had a stronger ability to acidize medium. Furthermore, in the aap2 mutants, polar auxin transport was disrupted in the root tip, leading to high auxin levels in roots. Interestingly, slightly alkaline media rescued their severely reduced root growth by stimulating auxin pathway.

Fatty Acid Binding Protein 5 (FABP5) Promotes Aggressiveness of Gastric Cancer Through Modulation of Tumor Immunity.

PURPOSE: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. MATERIALS AND METHODS: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). RESULTS: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokine-cytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. CONCLUSIONS: These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.

Factors influencing the quality of sexual life in the older adults: A scoping review.

Objective: Older people are often considered asexual, but sex is still important for older adults. So, this review aimed to analyze relevant studies on the sexual life of older adults to clarify factors, and provide a basis for their quality of sexual life. Method: A scoping review was performed according to Arksey and O'Malley's framwork, aiming to identify eligible research studies in PubMed, Web of Science, CINAHL, and PsycINFO, Cochrane Library, and Scopus databases. Peer-reviewed articles published in Chinese or English language from January 2012 to April 2022 were retrieved. All of identified studies were screened, extracted, and analyzed independently by two researchers. Result: A total of 7,374 studies were retrieved, and 13 eligible studies were finally included. The factors affect the sexual quality of life in older adults that included physiological, sociocultural, and health factors and being affected by marital relationships and a lack of relevant knowledge. Conclusion: The factors that affect the quality of old people's sex life interact and influence each other. Medical and health professionals can assist with the improvement of sexual health.

High-Q chalcogenide racetrack resonators based on the multimode waveguide.

We propose and demonstrate a high quality (Q) factor racetrack resonator based on uniform multimode waveguides in high-index contrast chalcogenide glass film. Our design features two carefully designed multimode waveguide bends based on modified Euler curves, which enable a compact 180° bend and reduce the chip footprint. A multimode straight waveguide directional coupler is utilized to couple the fundamental mode without exciting higher-order modes in the racetrack. The fabricated micro-racetrack resonator shows a record-high intrinsic Q of 1.31×106 for selenide-based devices, with a relatively low waveguide propagation loss of only 0.38 dB/cm. Our proposed design has potential applications in power-efficient nonlinear photonics.

Efficacy and safety of negative allosteric modulators of 5-hydroxytryptamine 2A receptors in the treatment of Alzheimer's disease psychosis: A systematic review and meta-analysis.

BACKGROUND: Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors are located postsynaptically to serotonergic neurons in the frontal cortex and mediate both excitatory and inhibitory neurotransmissions. However, the effectiveness and tolerance of negative modulators of 5-HT2A receptors in Alzheimer's disease psychosis (ADP) are uncertain. OBJECTIVES: To detect the negative modulators of the 5-HT2A receptor as a cure for ADP. MATERIAL AND METHODS: The primary outcome indicator was the total Neuropsychiatric Inventory (NPI) score. Other prognostic indicators included Mini-Mental State Examination (MMSE), the Katz Index of Independence in Activities of Daily Living (KATZ), the discontinuation rate, and adverse events. RESULTS: Compared to placebo, 5-HT2A inverse agonists significantly reduced the NPI total score, the KATZ and the MMSE score. The pooled odds ratio (OR) was 1.64 (95% confidence interval (95% CI): 1.01-2.65) and the heterogeneity variance was estimated at Tau2 = 0.52 with an I2 value of 90%, a χ2 value of 111.31, p = 0.04, and z-value of 2.01. The risk difference (RD) between the 5-HT2A receptor negative modulators and placebo groups was 0.12 (95% CI: 0.00-0.24) and the heterogeneity was estimated at Tau2 = 0.03, χ2 value of 127.23, degrees of freedom (df) value of 9, I2 value of 93%, z-value of 1.92, and p-value of 0.01 (<0.05). CONCLUSION: Our results suggest that negative modulators of 5-HT2A receptors are beneficial and well-tolerated in the treatment of ADP.

[Advances in Molecular Targeted Ultrasound Contrast Agents].

In real-time ultrasound,molecular targeted contrast agent is introduced into the blood circulation through peripheral intravenous injection to enhance the imaging signal of target lesions after binding to the corresponding intravascular receptors,which can realize early diagnosis,staging of diseases,assessment of treatment response,and targeted treatment.In addition,molecular targeted ultrasound contrast agents provide a platform for the delivery of drugs and genes via microbubbles,and nanoscale contrast agents can be infiltrated through vascular endothelium into the interstitial space of the lesion for imaging or treatment.The available studies of molecular targeted ultrasound contrast agents mainly focus on the preclinical trials.Some clinical trials have been conducted in humans and preliminarily confirm the safety and feasibility of targeted ultrasound contrast agents.The molecular targeted ultrasound contrast agents enjoy a broad prospect in clinical application.

[Effect of circRASA2 targeting miR-543/TRAF6 axis on LPS-induced periodontal ligament cell proliferation and osteogenic differentiation].

PURPOSE: To investigate the possible role of circRASA2 in periodontitis and its potential regulatory mechanism. METHODS: Periodontitis cell model was established by lipopolysaccharide(LPS)-induced periodontal ligament cells(PDLCs). Cell proliferation activity was detected by CCK-8 assay, cell migration ability was detected by Transwell chamber assay, and the expression of osteogenic differentiation-related proteins in cells was detected by Western blot. The target miRNA of circRASA2 and its downstream target genes were predicted using the databases circinteractome and starBase, respectively, and the targeting relationship between the target genes was verified by dual-luciferase reporter gene experiment. GraphPad Prism 8.0 software package was used to analyze the data. RESULTS: circRASA2 was highly expressed in LPS-treated PDLCs cells. LPS-induced PDLCs cell proliferation activity, migration ability and osteogenic differentiation ability decreased, while knockdown of circRASA2 promoted proliferation, migration and osteogenic differentiation ability of PDLCs under LPS treatment. circRASA2 targeted and negatively regulated the expression of miR-543, and overexpression of miR-543 promoted proliferation, migration and osteogenic differentiation of PDLCs under LPS treatment. TRAF6 was a downstream target gene of miR-543, knockdown of circRASA2 down-regulated the expression of TRAF6 through the sponge action of miR-543. Overexpression of TRAF6 reversed the promotion of circRASA2 knockdown on proliferation, migration and osteogenic differentiation of PDLCs. CONCLUSIONS: circRASA2 accelerated the pathological process of periodontitis in vitro through miR-543/TRAF6 axis, and might improve periodontitis by targeting down the expression of circRASA2.

Long-term results of radiofrequency ablation for locally recurrent papillary thyroid carcinoma.

OBJECTIVE: To evaluate the long-term efficacy and safety of ultrasound-guided radiofrequency ablation (RFA) for treating locally recurrent papillary thyroid cancer (PTC). METHODS: This retrospective study involved 32 patients with pathologically confirmed locally recurrent PTC. The ablation zone was assessed by contrast-enhanced ultrasound (CEUS) after RFA. At baseline, 6 and 12 months and every 6 months or 12 months thereafter, the following results were recorded: recurrence rate, largest diameter, volume, volume reduction rate (VRR) of recurrent lesions, serum thyroglobulin (Tg) level and complications. RESULTS: 58 recurrent lesions in 32 patients were successfully ablated with RFA. The mean follow-up time was 73.19 ± 12.68 months (range, 60 to 98 months). At the last follow-up, almost all ablated lesions disappeared completely, and only one lesion showed scar-like changes. Nine (28.13%) patients developed new locally recurrent tumors; they were successfully treated with repeat RFA sessions. No new recurrent lesions were found during the follow-up. The largest diameter and volume of recurrent lesions decreased from 13.71 ± 6.48 mm and 520.43 ± 627.85 mm3 to 0 each at the end of observation period (p < .001). The average VRRs at 6, 12, 24, 36, 48, 60 months and last follow-up after RFA were 54.17%, 72.90%, 82.28%, 89.30%, 92.57%, 96.60%, 96.88%, 98.14% and 100% respectively. The median of serum Tg level was decreased from 1.48 ng/mL to 0.00 ng/mL (p < .05). No complications were reported during the follow-up. CONCLUSIONS: US-guided RFA is an effective and safe option for treating locally recurrent PTC in selected patients, with favorable long-term outcomes.

Achieving Free-Standing PEDOT:PSS Solar Generators with Efficient All-in-One Photothermoelectric Conversion.

Poly(3,4-ethylene dioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) has attracted widespread attention in solar generation due to its unique all-in-one photothermoelectric effect. However, the poor photothermal conversion, low conductivity, and unsatisfied mechanical properties limit its practical application. Herein, ionic liquids (IL) were first used to improve the conductivity of PEDOT:PSS through ion exchange, then surface-charged nanoparticles SiO2-NH2 (SiO2+) were added to promote the dispersion of IL and as a thermal insulator to decrease thermal conductivity. It resulted in a largely enhanced electrical conductivity and decreased thermal conductivity of PEDOT:PSS simultaneously. The obtained PEDOT:PSS/Ionic Liquid/SiO2+ (P_IL_SiO2+) film generated an excellent photothermal conversion of 46.15 °C, which improved ∼134 and ∼82.3% compared with PEDOT:PSS and PEDOT:PSS/Ionic Liquid (P_IL) composites, respectively. In addition, the thermoelectric performance increased by ∼270% more than P_IL films. As a result, the photothermoelectric effect for the self-supported three-arm devices produced an enormous output current and power of ∼50 µA and 13.57 nW, respectively, which showed significant improvement compared with other PEDOT:PSS films reported in the literature. Furthermore, the devices demonstrated outstanding stability with an internal resistance variation of less than 5% after 2000 cycles of bending. Our research offered significant insights into the flexible, high-performance, all-in-one photothermoelectric integration.

CEP55: an immune-related predictive and prognostic molecular biomarker for multiple cancers.

BACKGROUND: Centrosomal protein 55 (CEP55) plays a significant role in specific cancers. However, comprehensive research on CEP55 is lacking in pan-cancer. METHODS: In-house and multi-center samples (n = 15,823) were used to analyze CEP55 in 33 cancers. The variance of CEP55 expression levels among tumor and control groups was evaluated by the Wilcoxon rank-sum test and standardized mean difference (SMD). The clinical value of CEP55 in cancers was assessed using receiver operating characteristic (ROC) curves, Cox regression analysis, and Kaplan-Meier curves. The correlations between CEP55 expression and the immune microenvironment were explored using Spearman's correlation coefficient. RESULTS: The data of clustered regularly interspaced short palindromic repeats confirmed that CEP55 was essential for the survival of cancer cells in multiple cancer types. Elevated CEP55 mRNA expression was observed in 20 cancers, including glioblastoma multiforme (p < 0.05). CEP55 mRNA expression made it feasible to distinguish 21 cancer types between cancer specimens and their control samples (AUC = 0.97), indicating the potential of CEP55 for predicting cancer status. Overexpression of CEP55 was correlated with the prognosis of cancer individuals for 18 cancer types, exhibiting its prognostic value. CEP55 expression was relevant to tumor mutation burden, microsatellite instability, neoantigen counts, and the immune microenvironment in various cancers (p < 0.05). The expression level and clinical relevance of CEP55 in cancers were verified in lung squamous cell carcinoma using in-house and multi-center samples (SMD = 4.07; AUC > 0.95; p < 0.05). CONCLUSION: CEP55 may be an immune-related predictive and prognostic marker for multiple cancers, including lung squamous cell carcinoma.

A Novel Spectral Index for Tracking Preload Change from a Wireless, Wearable Doppler Ultrasound.

A wireless, wearable Doppler ultrasound offers a new paradigm for linking physiology to resuscitation medicine. To this end, the image analysis of simultaneously-acquired venous and arterial Doppler spectrograms attained by wearable ultrasound represents a new source of hemodynamic data. Previous investigators have reported a direct relationship between the central venous pressure (CVP) and the ratio of the internal jugular-to-common carotid artery diameters. Because Doppler power is directly related to the number of red cell scatterers within a vessel, we hypothesized that (1) the ratio of internal jugular-to-carotid artery Doppler power (V/APOWER) would be a surrogate for the ratio of the vascular areas of these two vessels and (2) the V/APOWER would track the anticipated CVP change during simulated hemorrhage and resuscitation. To illustrate this proof-of-principle, we compared the change in V/APOWER obtained via a wireless, wearable Doppler ultrasound to B-mode ultrasound images during a head-down tilt. Additionally, we elucidated the change in the V/APOWER during simulated hemorrhage and transfusion via lower body negative pressure (LBNP) and release. With these Interesting Images, we show that the Doppler V/APOWER ratio qualitatively tracks anticipated changes in CVP (e.g., cardiac preload) which is promising for both diagnosis and management of hemodynamic unrest.

In Situ Formation of Conductive Epidermal Electrodes Using a Fully Integrated Flexible System and Injectable Photocurable Ink.

In situ fabrication of wearable devices through coating approaches is a promising solution for the fast deployment of wearable devices and more adaptable devices for different sensing demands. However, heat, solvent, and mechanical sensitivity of biological tissues, along with personal compliance, pose strict requirements for coating materials and methods. To address this, a biocompatible and biodegradable light-curable conductive ink and an all-in-one flexible system that conducts in situ injection and photonic curing of the ink as well as monitoring of biophysiological information have been developed. The ink can be solidified through spontaneous phase changes and photonic cured to achieve a high mechanical strength of 7.48 MPa and an excellent electrical conductivity of 3.57 × 105 S/m. The flexible system contains elastic injection chambers embedded with specially designed optical waveguides to uniformly dissipate visible LED light throughout the chambers and rapidly cure the ink in 5 min. The resulting conductive electrodes offer intimate skin contact even with the existence of hair and work stably even under an acceleration of 8 g, leading to a robust wearable system capable of working under intense motion, heavy sweating, and varied surface morphology. Similar concepts may lead to various rapidly deployable wearable systems that offer excellent adaptability to different monitoring demands for the health tracking of large populations.

Furan Synthesis via a Tandem 1,2-Acyloxy Migration/[3 + 2] Cycloaddition/Aromatization of Enol Ether-Tethered Propargylic Esters.

An effective method for the synthesis of furans is developed via a tandem 1,2-acyloxy migration/intramolecular [3 + 2] cycloaddition/aromatization of enol ether-tethered propargylic esters. The reaction exhibits excellent functional group tolerance, broad substrate scope, and excellent chemoselectivity. The isolation of dihydrofuran intermediates in some cases gives more insight into the [3 + 2] cycloisomerization process.

[Effects of 24 Years Different Straw Return on Soil Carbon, Nitrogen, Phosphorus, and Extracellular Enzymatic Stoichiometry in Dryland of the Loess Plateau, China].

Exploring the biogeochemical cycle characteristics of soil carbon, nitrogen, and phosphorus in farmland in the dryland of the loess plateau can provide scientific basis and technical support for efficient crop production and sustainable land use. Here, based on a long-term (24 year) straw return field experiment in Shouyang, Shanxi province, the effects of different straw return regimes, i.e., straw mulching (SM), direct straw return (DS), animal-digested straw return (AS), and non-straw return (CK), on the stoichiometric ratio of soil elements and extracellular enzyme activities were studied. The vector angle and length were calculated to indicate the resource constraints faced by microorganisms. The vector angle was greater than 45° and less than 45°, indicating that microorganisms were limited by phosphorus and nitrogen, respectively. The greater the deviation from 45°, the greater the degree of limitation, and the longer the vector length, the more severely limited by carbon. The results showed that ① the soil C/N and C/P of long-term straw returning ranged from 9.81 to 14.28 and from 14.58 to 21.92, with the mean values of 12.36 and 17.51, respectively, which were 6.0% and 4.2% lower than that at the initial stage of the experiment. The soil N/P was distributed between 1.27 and 1.57, with an average of 1.42, which was 2.2% higher than that in the initial stage. The soil C/N and C/P ratios showed a trend of first decreasing and then increasing, the soil N/P ratio basically showed a flat trend, and there was no significant difference in soil element metering ratios between different straw returning treatments. ② Compared with the 24-year long-term non-straw return treatment, the activities of ß-1,4-glucosidase (BG) and ß-1,4-N-acetylglucosaminidase (NAG) in the soil of the long-term straw mulching treatment increased by 134.4% and 107.5% (P<0.05), the activities of BG and alkaline phosphatase (AP) in the soil of the long-term straw mulching treatment decreased by 59.3% and 59.5% (P<0.05), respectively, and the activities of NAG in the soil of the long-term straw mulching treatment increased by 102.8% (P<0.05). Under the long-term straw returning treatment, soil microorganisms were faced with carbon and phosphorus limitation as a whole. Long-term straw mulching aggravated microbial carbon limitation, and animal-digested straw return could alleviate the degree of carbon limitation. Compared with that in the 24-year long-term non-straw return treatment, soil EEAC/N could be significantly reduced by the animal-digested straw return treatment, and soil EEAC/P could be increased by the direct straw return treatment. The three straw returning methods had no significant indigenous effect on soil EEAN/P. The overall vector angle was greater than 45°, and the vector length increased by 3.8%-20.1% compared with that in the initial stage. ③ Correlation analysis showed that C and N inputs were significantly negatively correlated with BG activity; available nitrogen was significantly correlated with NAG activity, AP activity, and EEAC/N; C/P was significantly positively correlated with EEAC/N; there were significant correlations between N/P and NAG activity, AP activity, EEAC/N, and EEAC/P; and there was no significant correlation between EEAN/P and any environmental factors. In conclusion, the availability of soil nitrogen and phosphorus elements and N/P ratio had significant effects on soil extracellular enzyme activity and stoichiometric characteristics under different long-term straw returning treatments. In the future, more attention should be paid to the improvement of organic carbon and the promotion of nitrogen and phosphorus availability in farmland soil in soil-efficient cultivation and agricultural production activities.

ALDOB represents a potential prognostic biomarker for patients with clear cell renal cell carcinoma.

Background: Previous studies have shown that aldolase B (ALDOB) might play controversial roles in multiple types of cancer, which could act as a cancer-promoting factor or a cancer-inhibiting factor depending on the subtype of the cancer. However, the role of ALDOB in clear cell renal cell carcinoma (ccRCC) patients has not been clearly elucidated. Therefore, this study aimed to comprehensively explore the expression level, prognostic value, functional enrichment, immune infiltration, and N6-methyladenosine (m6A) modification of ALDOB in ccRCC patients. Methods: A total of 1,070 ccRCC tissues and 409 normal tissues from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database, and the ArrayExpress database were enrolled to evaluate the expression level and prognostic value of ALDOB in ccRCC. The Kaplan-Meier survival curves and the Log-Rank test were performed to assess the prognostic value. The univariate and multivariate Cox regression analysis were used to identify the independent prognostic predictors in ccRCC patients. In addition, R version 4.2.0 with its suitable packages were used to perform the functional enrichment analysis, immune infiltration analysis, and m6A methylation analysis. Statistical significance was set at the P value <0.05. Results: The expression level of ALDOB was significantly down-regulated in ccRCC compared to normal tissue, and the ALDOB expression level was noticeably correlated with T stage, M stage, and histologic grade of patients with ccRCC. The survival analysis revealed that ALODB was the independent predictor of overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) of ccRCC patients. In addition, the functional enrichment analysis showed that ALDOB and its related genes were mainly involved in the metabolism and metabolic pathways of multiple substances, including glycolysis, gluconeogenesis, and fatty acid degradation. Finally, the immune infiltration analysis and the m6A methylation analysis suggested that ALDOB was closely correlated with the infiltration abundance of immune cells and stromal cells in the tumor microenvironment and several types of m6A regulators in ccRCC. Conclusions: As a potential prognostic biomarker for patients with ccRCC, downregulation of ALDOB was closely associated with the clinicopathological features, poor prognosis, immune infiltration, and m6A modification in ccRCC patients.

Strategic Design of Conquering Hypoxia in Tumor for Advanced Photodynamic Therapy.

Photodynamic therapy (PDT), with its advantages of high targeting, minimally invasive, and low toxicity side effects, has been widely used in the clinical therapy of various tumors, especially superficial tumors. However, the tumor microenvironment (TME) presents hypoxia due to the low oxygen (O2 ) supply caused by abnormal vascularization in neoplastic tissues and high O2 consumption induced by the rapid proliferation of tumor cells. The PDT process generally relies on the presence of O2 , so the efficacy of PDT can be hampered by a hypoxic TME. To address this problem, researchers have been developing advanced nanoplatforms and strategies to enhance the therapeutic effect of PDT in tumor treatment. This review summarizes recent advanced PDT therapeutic strategies to against the hypoxic TME during the PDT treatment, thus enhancing PDT efficacy, including increasing O2 content in TME through delivering O2 to the tumors and in situ generations of O2 ; decreasing the O2 consumption during PDT by design of type I photosensitizers. To boost the PDT therapeutic effect, recent synergistically combination therapy of PDT and other therapeutic methods such as chemotherapy, photothermal therapy (PTT), immunotherapy, gas therapy is accounted by addressing the challenging problems of mono PDT in hypoxic environments, including tumor resistance, proliferation, and metastasis. Finally, we provide perspectives of the opportunities and challenges of PDT in future clinical research and translations. This article is protected by copyright. All rights reserved.

Detecting the Change in Total Circulatory Flow with a Wireless, Wearable Doppler Ultrasound Patch: A Pilot Study.

Measuring fluid responsiveness is important in the management of critically ill patients, with a 10-15% change in cardiac output typically being used to indicate "fluid responsiveness." Ideally, these changes would be measured noninvasively and peripherally. The aim of this study was to determine how the common carotid artery (CCA) maximum velocity changes with total circulatory flow when confounding factors are mitigated and determine a value for CCA maximum velocity corresponding to a 10% change in total circulatory flow. DESIGN: Prospective observational pilot study. SETTING: Patients undergoing elective, on-pump coronary artery bypass grafting (CABG) surgery. PATIENTS: Fourteen patients were referred for elective coronary artery bypass grafting surgery. INTERVENTIONS: Cardiopulmonary bypass (CPB) pump flow changes during surgery, as chosen by the perfusionist. MEASUREMENTS: A hands-free, wearable Doppler patch was used for CCA velocity measurements with the aim of preventing user errors in ultrasound measurements. Maximum CCA velocity was determined from the spectrogram acquired by the Doppler patch. CPB flow rates were recorded as displayed on the CPB console, and further measured from the peristaltic pulsation frequency visible on the recorded Doppler spectrograms. MAIN RESULTS: Changes in CCA maximum velocity tracked well with changes in CPB flow. On average, a 13.6% change in CCA maximum velocity was found to correspond to a 10% change in CPB flow rate. CONCLUSIONS: Changes in CCA velocity may be a useful surrogate for determining fluid responsiveness when user error can be mitigated.