Erratum: Author correction to 'VEGFR2-targeted antibody fused with IFNamut regulates the tumor microenvironment of colorectal cancer and exhibits potent anti-tumor and anti-metastasis activity' [Acta Pharm Sin B 11 (2021) 420-433].

[This corrects the article DOI: 10.1016/j.apsb.2020.09.008.].

Hydrogen-rich water alleviates constipation by attenuating oxidative stress through the sirtuin1/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signaling pathway.

BACKGROUND: Constipation, a highly prevalent functional gastrointestinal disorder, induces a significant burden on the quality of patients' life and is associated with substantial healthcare expenditures. Therefore, identifying efficient therapeutic modalities for constipation is of paramount importance. Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms. Consequently, we postulate that hydrogen therapy, an emerging and promising intervention, can serve as a safe and efficacious treatment for constipation. AIM: To determine whether hydrogen-rich water (HRW) alleviates constipation and its potential mechanism. METHODS: Constipation models were established by orally loperamide to Sprague-Dawley rats. Rats freely consumed HRW, and were recorded their 24 h total stool weight, fecal water content, and charcoal propulsion rate. Fecal samples were subjected to 16S rDNA gene sequencing. Serum non-targeted metabolomic analysis, malondialdehyde, and superoxide dismutase levels were determined. Colonic tissues were stained with hematoxylin and eosin, Alcian blue-periodic acid-Schiff, reactive oxygen species (ROS) immunofluorescence, and immunohistochemistry for cell growth factor receptor kit (c-kit), PGP 9.5, sirtuin1 (SIRT1), nuclear factor-erythroid-2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1, Nrf2 and HO-1. A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor, EX527, into constipated rats. NCM460 cells were induced with H2O2 and treated with the metabolites to evaluate ROS and SIRT1 expression. RESULTS: HRW alleviated constipation symptoms by improving the total amount of stool over 24 h, fecal water content, charcoal propulsion rate, thickness of the intestinal mucus layer, c-kit expression, and the number of intestinal neurons. HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism. HRW could also reduce intestinal oxidative stress through the SIRT1/Nrf2/HO-1 signaling pathway. This regulatory effect on oxidative stress was confirmed via an intraperitoneal injection of a SIRT1 inhibitor to constipated rats. The serum metabolites, ß-leucine (ß-Leu) and traumatic acid, were also found to attenuate H2O2-induced oxidative stress in NCM460 cells by up-regulating SIRT1. CONCLUSION: HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway, modulating gut microbiota and serum metabolites. ß-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress.

Soluble Programmed Cell Death 1 Protein Is a Promising Biomarker to Predict Severe Liver Inflammation in Chronic Hepatitis B Patients.

Background and Aims: Liver inflammation is important in guiding the initiation of antiviral treatment and affects the progression of chronic hepatitis B(CHB). The soluble programmed cell death 1 protein (sPD-1) was upregulated in inflammatory and infectious diseases and correlated with disease severity. We aimed to investigate the correlation between serum sPD-1 levels and liver inflammation in CHB patients and their role in indicating liver inflammation. Methods: 241 CHB patients who underwent liver biopsy were enrolled. The correlation between sPD-1 levels and the degree of liver inflammation was analyzed. Univariate and multivariate logistic regression analyses were performed to analyze independent variables of severe liver inflammation. Binary logistic regression analysis was conducted to construct a predictive model for severe liver inflammation, and the receiver operating characteristic curve (ROC) was used to evaluate the diagnostic accuracy of the predictive model. Results: sPD-1 was highest in CHB patients with severe liver inflammation, which was higher than that in CHB patients with mild or moderate liver inflammation (P < 0.001). Besides, sPD-1 was weakly correlated with AST (r = 0.278, P < 0.001). Multivariable analysis showed that sPD-1 was an independent predictor of severe liver inflammation. The predictive model containing sPD-1 had areas under the ROC (AUROCs) of 0.917 and 0.921 in predicting severe liver inflammation in CHB patients and CHB patients with ALT ≤ 1× upper limit of normal (ULN), respectively. Conclusions: Serum sPD-1 level is associated with liver inflammation in CHB patients, and high levels of sPD-1 reflect severe liver inflammation. Serum sPD-1 is an independent predictor of severe liver inflammation and shows improved diagnostic accuracy when combined with other clinical indicators.

What motivates information (non-)seeking behaviors about a healthy diet?

Previous research on health information seeking has primarily focused on individuals'intentions to seek or avoid information. However, limited empirical evidence exists regarding the actual behavioral patterns of information-seeking and non-seeking. To address this, we conducted a survey experiment manipulating cognitive load with mostly Belgian participants (N = 359). By integrating self-report and behavioral data, we investigated motivations and conditions associated with information (non)-seeking behaviors on a healthy diet. Guided by the risk information seeking and processing (RISP) model, we examined the roles of informational subjective norms and information insufficiency, as well as the moderating role of cognitive capacity. Neither informational subjective norms nor information insufficiency significantly correlated with information-seeking behaviors. However, a significant interaction between the predictors and cognitive capacity in predicting non-seeking behaviors was observed. These findings underscore the intricate nature of individuals' behavioral patterns in seeking or not seeking information about healthy eating.

Evaluation of a Novel Microfocused Ultrasound with Three-Dimensional Digital Imaging for Facial Tightening: A Prospective, Randomized, Controlled Trial.

BACKGROUND: The excellent efficacy is mitigated by the limited safety profile of microfocused ultrasound procedures. OBJECTIVE: We sought to assess the safety and tightening efficacy of a novel microfocused ultrasound. METHODS: The randomized middle and lower face and submental region of the participants were treated with the novel device using the following transducers: M4.5, D4.5, M3.0, and D3.0. Improvement in paired comparison of pretreatment and posttreatment photographs, three-dimensional (3D) volumetric assessments, skin thickness measured by B-ultrasonography, and skin photoaging parameters were evaluated. Adverse events and patient satisfaction were also recorded. RESULTS: A total of 20 participants (20 female) were enrolled. Fourteen of 20 participants (70%) were judged to show clinically significant facial tightening during 3-month follow-up (P < 0.05). The mean volumetric change in the lower face, as quantitatively assessed after 3 months was -0.29 mL compared with +0.42 mL on the control side (P < 0.05). The VAS pain score was 3.00 ± 1.19 without any oral or intramuscular anesthesia. CONCLUSIONS: A small sample size, lack of clinical scales, and impersonalized treatment parameters. The novel microfocused ultrasound appears to be a safe and effective modality for lower-face tightening. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR 2200064666.

Dendrite-Free Zinc Anodes Enabled by Exploring Polar-Face-Rich 2D ZnO Interfacial Layers for Rechargeable Zn-Ion Batteries.

Zinc metal is a promising candidate for anodes in zinc-ion batteries (ZIBs), but its widespread implementation is hindered by dendrite growth in aqueous electrolytes. Dendrites lead to undesirable side reactions, such as hydrogen evolution, passivation, and corrosion, causing reduced capacity during prolonged cycling. In this study, an approach is explored to address this challenge by directly growing 1D zinc oxide (ZnO) nanorods (NRs) and 2D ZnO nanoflakes (NFs) on Zn anodes, forming artificial layers to enhance ZIB performance. The incorporation of ZnO on the anode offers both chemical and thermal stability and leverages its n-type semiconductor nature to facilitate the formation of ohmic contacts. This results in efficient electron transport during Zn ion plating and stripping processes. Consequently, the ZnO NFs-coated Zn anodes demonstrate significantly improved charge storage performance, achieving 348 mAh g-1 , as compared to ZnO NRs (250 mAh g-1 ) and pristine Zn (160 mAh g-1 ) anodes when evaluated in full cells with V2 O5 cathodes. One significant advantage of ZnO NFs lies in their highly polar surfaces, promoting strong interactions with water molecules and rendering them exceptionally hydrophilic. This characteristic enhances the ability of ZnO NFs to desolvate Zn2+ ions, leading to improved charge storage performance.

Effect of serum autoantibodies on the COVID-19 patient's prognosis.

Objectives: Virus infection closely associated with autoimmune disease. The study aimed to explore the autoantibody profiles and the correlation of autoantibodies with the disease severity and the prognosis of the coronavirus disease 2019 (COVID-19) patients. Methods: Three hundred thirty-seven hospitalized COVID-19 patients from 6th to 23rd January 2023 were enrolled. Logistic and Cox regression analyses were used to analyze the risk factors for the patient's disease severity and outcome. The association between Anti-extractable nuclear antigen antibody (ENA) positivity and the prognosis of COVID-19 patients was analyzed using Kaplan-Meier survival curves. Results: 137 of COVID-19 patients were detected positive for antinuclear antibody (ANA), 61 had positive results for ENA, and 38 were positive for ANA and ENA. ANA positivity rate was higher in non-severe illness group (p = 0.032). COVID-19 patients who died during hospitalization had a high rate of ENA positivity than convalescent patients (p = 0.002). Multivariate logistic regression showed that ANA positivity was a protective factor for the disease severity of COVID-19. Multivariate Cox regression analysis revealed that ENA positivity, white blood cells count (WBC), aspartate aminotransferase (AST), Creatinine (CREA), and CRP were independent risk factors for the outcome of COVID-19 patients, and that COVID-19 patients with ENA positivity had a lower cumulative survival rate (p = 0.002). Conclusion: A spectrum of autoantibodies were expressed in COVID-19 patients, among which ANA and ENA positivity was associated with the severity and prognosis of COVID-19. Therefore, autoantibodies may help to assess the disease severity and prognosis of COVID-19 patients.

The presence of baseline HBsAb-Specific B cells can predict HBsAg or HBeAg seroconversion of chronic hepatitis B on treatment.

Indices for predicting HBsAg or HBeAg seroconversion in patients with chronic hepatitis B virus (HBV) infection during antiviral therapy remain elusive. We aimed to investigate if the presence of HBsAb-specific B cells at baseline can predict HBsAg or HBeAg seroconversion. In this study, 134 treatment-naive patients with chronic HBV were enrolled. A baseline HBsAb-specific B cell ELISpot assay was performed for all the patients that enrolled. Serum samples were collected at 12, 24, and 48 weeks for patients treated with Peg-IFN-α, or at 1 year, 3 years, and 5 years for patients treated with NAs. Laboratory testing of HBsAg, HBsAb, HBeAg, HBeAb, HBcAb, HBV DNA, ALT, and AST was done. We observed a significantly lower frequency of HBsAb-specific B cells in patients with chronic HBV than in healthy individuals . In the Peg-IFN-α-treated group, 41.2% of patients with baseline HBsAb-specific B cells achieved HBsAg seroconversion, while only 13.6% of patients without baseline HBsAb-specific B cells achieved HBsAg seroconversion (p = 0.006). By logistic regression analysis, patients with baseline HBsAb-specific B cells and HBsAg ≤ 1500 had higher HBsAg clearance at the end of treatment (p < 0.05). In the NA-treated group, 58.3% of patients with baseline HBsAb-specific B cells achieved HBeAg seroconversion, whereas only 30.0% of patients without baseline HBsAb-specific B cells achieved HBeAg seroconversion (p = 0.114). Our result revealed that baseline HBsAb-specific B cells by ELISpot assay might be a valuable predictive biomarker of HBsAg or HBeAg seroconversion in patients with chronic HBV on treatment.

Clinical value of droplet digital PCR in the diagnosis and dynamic monitoring of suspected bacterial bloodstream infections.

BACKGROUND: Bloodstream infections (BSIs) represent a significant public health challenge due to their high morbidity and mortality. The clinical prognosis of BSIs is closely related to the timely and accurate diagnosis and the rational use of initial antimicrobials. We aimed to evaluate the clinical value of droplet digital PCR (ddPCR) in rapid diagnosis and dynamic monitoring of BSIs. METHODS: In this prospective study, using a ddPCR-based approach which detects 18 common pathogens, we compared the detection results and clinical concordance rates of ddPCR with blood culture (BC) in 211 patients with suspected BSIs. Further, the inflammatory profile of BSIs with Gram-negative bacteria was analyzed by Olink proteomics platform. RESULTS: Our data showed that the positive detection rate of ddPCR was 48.82%, which was higher than that of BC (9.48%). For BC-validated BSIs, ddPCR had a sensitivity of 90.00% and a specificity of 55.50%. When considering clinically-validated BSIs, the diagnostic value of ddPCR improved with a sensitivity of 92.59% and a specificity of 78.46%.The bacterial load detected by ddPCR was correlated with traditional clinical inflammatory indicators such as interleukin-6 (IL-6) and C-reactive protein (CRP). In addition, using Olink proteomics platform, we revealed that serological osteoprotegerin (OPG), interleukin-8 (IL-8), interleukin-18 receptor 1 (IL-18R1), C-C motif chemokine 20 (CCL20) and IL-6 were substantially elevated in Gram-negative bacteria-associated BSIs, which could serve as novel auxiliary diagnostic indicators for Gram-negative bacteria BSIs. CONCLUSION: ddPCR has the potential to provide early pathogen diagnosis, dynamic monitoring, and treatment regimen optimization for patients with BSIs.

One-pot solvothermal synthesis of flower-like Fe-doped In2S3/Fe3S4 S-scheme hetero-microspheres with enhanced interfacial electric field and boosted visible-light-driven CO2 reduction.

S-scheme heterojunctions hold great potential for CO2 photoreduction into solar fuels, but their activities are severely limited by the low efficiency of interfacial charge transfer. In this work, a facile one-pot solvothermal reaction has been developed to dope Fe into flower-like In2S3/Fe3S4 hetero-microspheres (Fe-In2S3/Fe3S4 HMSs), which are demonstrated as an efficient S-scheme photocatalyst for visible-light-driven CO2 photoreduction. The doping of Fe not only reduces the bandgap of In2S3 and thus extends the optical response to the visible-light region, but also increases the densities of donors and sulfur vacancies, which leads to an elevated Fermi level (Ef). The difference of Ef between In2S3 and Fe3S4 is enlarged and their band bending at the interface is therefore enhanced, which results in promoted carriers transfer in the S-scheme pathway due to the reinforced interfacial electric field. Moreover, Fe-doped In2S3 reduces the formation energy of the *CO intermediate, which thermodynamically favors the CO evolution at the surface. As a result, the Fe-In2S3/Fe3S4 HMSs exhibit a significantly boosted CO2 photoreduction activity in comparison with bare In2S3 and Fe-In2S3 samples. This work demonstrates the great potential of heteroatom-engineered S-scheme photocatalysts for CO2 photoreduction.

Sesamol inhibits proliferation, migration and invasion of triple negative breast cancer via inactivating Wnt/ß-catenin signaling.

Triple negative breast cancer (TNBC), a particularly aggressive breast cancer subtype without estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2) expression, possesses highly invasive capacity, uncontrolled proliferative phenotype and poor clinical prognosis. Sesamol enriched in sesame seeds has been widely reported as a metabolic modulator due to its anti-aging, anti-hepatotoxic and cardio-protective properties. In this study, we found that sesamol significantly inhibited proliferation, migration and invasion of TNBC cells via attenuating PCNA, CyclinD1 expression and reversion of epithelial-mesenchymal transition (EMT) characterized by increased epithelial marker E-cadherin and decreased mesenchymal marker N-cadherin, Vimentin, Snail expression. Moreover, sesamol inactivated Wnt/ß-catenin signaling and Wnt agonist 1 AMBMP application reversed the inhibition of proliferation, migration and invasion of TNBC by sesamol administration. Subsequently, our data showed that sesamol induced Wnt inhibitory factor 1 (WIF1), an endogenous inhibitor of Wnt/ß-catenin pathway, expression and WIF1 artificial knockdown abrogated the inactivation of Wnt/ß-catenin signaling by sesamol exposure in TNBC cells. And we found that promoter region de-methylation was responsible for WIF1 up-regulation by sesamol administration. Finally, with the xenograft assay using nude mice, we also found that sesamol inhibited proliferation and metastasis of TNBC via WIF1-induced inactivation of Wnt/ß-catenin signaling in vivo. Collectively, these data added novel understandings and evidences to the anti-cancer properties of sesamol.

Theoretical understanding on all-solid frustrated Lewis pair sites of C2N anchored by single metal atom.

The design of all-solid heterogeneous catalysts with frustrated Lewis pairs (FLPs) has attracted much attention recently because of their appealing low dissociation energy for H2 molecules due to which a promotion of hydrogenation reaction is expected. The sterically encumbered Lewis acid (metal site) and base (nitrogen site) in the cavity of single transition metal atom-doped M/C2N sheets make them potential candidates for the design of catalysts with FLPs, while a comprehensive understanding of their intrinsic property and reactivity is still lacking. Calculations show that the complete dissociation of the H2 molecule into two H* states at the N sites requires two steps: heterolytic cleavage of the H2 molecule and the transfer of H* from the metal site to the N site, which are strongly related to the acidity of the metal site. Ni/C2N and Pd/C2N, which outperform the other eight transition metal atom (M) anchored M/C2N candidates, possess low energy barriers for the complete dissociation of H2 molecules, with values of only 0.30 and 0.20 eV, respectively. Furthermore, both Ni/C2N and Pd/C2N catalysts can achieve semi-hydrogenation of C2H2 into C2H4, with overall barriers of 0.81 and 0.75 eV, respectively, which are lower than those reported for many other catalysts. It is speculated that M/C2N catalysts with intrinsic FLPs may also find applications in other important hydrogenation reactions.

A Novel Study on Alar Mobility of HAN Female by 3dMD Dynamic Surface Imaging System.

AIM: The aim of this study is to conduct a quantitative analysis on alar mobility of HAN females and provided referenced materials for alar dynamic aesthetic. METHODS: One hundred and fifty healthy HAN females without rhinoplasty, nasal injury, nasal deformity and craniofacial deformity were included in this study. 3dMD surface imaging system was used for anthropometric analysis. All participants were instructed to perform the desired dynamic facial expression from rest to maximum smile without reveling teeth and recorded by 3dMD dynamic surface imaging system simultaneously. Two frames of rest status and alar maximum enlargement were selected for measuring alar width, alar base width and inner-canthal distance. The difference between two status represented alar mobility, which was generated through equation: [Formula: see text]. RESULTS: Alar mobility consisted of alar flaring mobility and alar base mobility. The alar flaring mobility was (9.49 ± 4.90)%, reference range was(1.45, 17.53)% and regression equation between rest and maximum smile was Y = 7.953 + 0.886X (R2 = 0.641, p = 0.000); the alar base mobility was (17.94 ± 10.44)%, reference range was (0.88, 35.00)% and regression equation between rest and maximum smile was Y = 4.481 + 0.966X (R2 = 0.528, p = 0.000. CONCLUSION: Asian alar anatomy has great distinction from Caucasian, processing conspicuous alar movement and damaging alar aesthetic dynamically. This study novelly defined alar mobility by three-dimensional anthropometric analysis, providing objective references for alar dynamic aesthetic and arousing plastic surgeons' attention on keeping balance of static and dynamic aesthetic in rhinoplasty. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A Novel Serum tsRNA for Diagnosis and Prediction of Nephritis in SLE.

Objective: Dysregulation of transfer RNA (tRNA)-derived small noncoding RNA (tsRNA) signatures in human serum has been found in various diseases. Here, we determine whether the signatures of tsRNAs in serum can serve as biomarkers for diagnosis or prognosis of systemic lupus erythematosus (SLE). Methods: Initially, small RNA sequencing was employed for the screening serum tsRNAs obtained from SLE patients, followed by validation with TaqMan probe-based quantitative reverse transcription-PCR (RT-PCR) assay. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic efficacy. The biological functions of tsRNAs were identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) assay. Results: We first analyzed tsRNA signatures in SLE serum and identified that tRF-His-GTG-1 was significantly upregulated in SLE serum. The combination of tRF-His-GTG-1 and anti-dsDNA could serve as biomarkers for diagnosing SLE with a high area under the curve (AUC) of 0.95 (95% CI = 0.92-0.99), sensitivity (83.72%), and specificity (94.19%). Importantly, the noninvasive serum tRF-His-GTG-1 could also be used to distinguish SLE with LN or SLE without LN with AUC of 0.81 (95% CI, 0.73-0.88) and performance (sensitivity 66.27%, specificity 96.15%). Moreover, the serum tsRNA is mainly secreted via exosome and can directly target signaling molecules that play crucial roles in regulating the immune system. Conclusion: In this study, it has been demonstrated for the first time that serum tsRNAs can be employed as noninvasive biomarkers for the efficient diagnosis and prediction of nephritis in SLE.

Single non-noble metal atom doped C2N catalysts for chemoselective hydrogenation of 3-nitrostyrene.

Improving the reaction selectivity and activity for challenging substrates such as nitroaromatics bearing two reducible functional groups is important in industry, yet remains a great challenge using traditional metal nanoparticle based catalysts. In this study, single metal atom doped M-C2N catalysts were theoretically screened for selective hydrogenation of 3-nitrostyrene to 3-vinylaniline with H2 as the H-source. Among 20 M-C2N catalysts, the non-noble Mn-C2N catalyst was found to have excellent reaction selectivity. Importantly, due to the solid frustrated Lewis pair sites in the pores of Mn-C2N, a low H2 activation energy is achieved on high-spin Mn-C2N and the rate-determining step for the hydrogenation reactions is the H diffusion from the metal site to the N site. The unraveled mechanism of the hydrogenation of 3-nitrostyrene using Mn-C2N enriches the applications of Mn based catalysts and demonstrates its excellent properties for catalyzing the challenging hydrogenation reaction of substrates with two reducible functional groups.

Sesamol Epigenetically Induces Estrogen Receptor α Re-expression by Upregulating miR-370-3p in Estrogen Receptor α-Negative Breast Cancer.

Due to lack of estrogen receptor α (ERα, gene name: ESR1), ERα-negative breast carcinoma is insensitive to endocrine therapy, and restoration of ERα has become a promising strategy for ERα-negative breast cancer treatment. Sesamol, a naturally occurring phenolic compound, is usually extracted from sesame seeds. Previous investigations have unmasked its anti-oxidant and anti-inflammation properties. In this study, sesamol induced ERα functional re-expression followed by upregulation of its downstream pS2 and GREB1 genes in ERα-negative breast carcinoma. Moreover, it endowed responsiveness of ERα-negative breast carcinoma to the endocrine treatment drug 4-hydroxytamoxifen without influencing the viability of normal human umbilical vein endothelial cells. Mechanistically, sesamol induced ESR1 gene promoter demethylation by downregulating the expression of the DNA methyltransferases DNMT3A and DNMT3B, without affecting DNMT1. Moreover, the non-coding RNA miR-370-3p directly targeted DNMT3A and DNMT3B mRNA, and its expression increased upon treatment with sesamol. Artificial abrogation of miR-370-3p expression with an antagomir abolished the inhibition of DNMT3A and DNMT3B expression by sesamol, resulting in a fallback in ERα reactivation. In mice, sesamol significantly induced ERα re-expression via miR-370-3p-mediated downregulation of DNMT3A and DNMT3B. Sesamol may be a safe and effective option for clinical adjuvant therapy in patients with ERα-negative breast cancer.

VEGFR2-targeted antibody fused with IFN α mut regulates the tumor microenvironment of colorectal cancer and exhibits potent anti-tumor and anti-metastasis activity.

Although interferon α (IFNα) and anti-angiogenesis antibodies have shown appropriate clinical benefit in the treatment of malignant cancer, they are deficient in clinical applications. Previously, we described an anti-vascular endothelial growth factor receptor 2 (VEGFR2)-IFNα fusion protein named JZA01, which showed increased in vivo half-life and reduced side effects compared with IFNα, and it was more effective than the anti-VEGFR2 antibody against tumors. However, the affinity of the IFNα component of the fusion protein for its receptor-IFNAR1 was decreased. To address this problem, an IFNα-mutant fused with anti-VEGFR2 was designed to produce anti-VEGFR2-IFNαmut, which was used to target VEGFR2 with enhanced anti-tumor and anti-metastasis efficacy. Anti-VEGFR2-IFNαmut specifically inhibited proliferation of tumor cells and promoted apoptosis. In addition, anti-VEGFR2-IFNαmut inhibited migration of colorectal cancer cells and invasion by regulating the PI3K-AKT-GSK3ß-snail signal pathway. Anti-VEGFR2-IFNαmut showed superior anti-tumor efficacy with improved tumor microenvironment (TME) by enhancing dendritic cell maturation, dendritic cell activity, and increasing tumor-infiltrating CD8+ T cells. Thus, this study provides a novel approach for the treatment of metastatic colorectal cancer, and this design may become a new approach to cancer immunotherapy.

Enophthalmos: Exploration of Quantitative Treatment With Retro-Orbital Fat Globules Injection.

Craniomaxillofacial and plastic surgeons are often confronted with patients who present with enophthalmos caused mainly by trauma. In many patients, one-stage reconstruction repairs only the bony orbit, leaving intact the disfiguring enophthalmos. Thus, some filler is needed to restore the normal volume of the orbit. The authors describe a technique to correct such deformation safely and effectively. Data were collected from 30 enophthalmic patients (average age 36.67 ±â€Š11.66 years) who underwent retro-ocular injections of fat globules between August 2014 and July 2018. CT helped identify a safe injection site, and specific CT measurements quantified the volume of fat globules required. There was a significant difference between the preoperative and postoperative values for lateral orbital protrusion (P < .01), superior orbital protrusion (P < .01), and orbital volume (P < .01). Most patients were satisfied with the outcome. There were no significant complications. Injecting fat globules into the retro-orbital area is an effective technique for correcting enophthalmos deformity.

[Assessing Performance of Pollutant Removal from Municipal Wastewater by Physical and Chemical Methods Based on Membranes].

The removal characteristics of various pollution factors in municipal wastewater by membrane-based physical and chemical treatment, especially the enrichment characteristics of dissolved organic matter, were investigated by high performance liquid chromatography and three-dimensional fluorescence spectroscopy. The results showed that the municipal wastewater had a low COD/TN ratio after the treatment. The micro-flocculation filtration mainly enriched the non-dissolvable organic matter in the raw water and aromatic protein substances with relative molecular mass greater than 30 000. The enrichment degree was up to 60.93%, especially for tyrosine-like and tryptophan-like substances. The dissolved organic matter (DOM) with a molecular weight greater than 30 000 was enriched fully by 0.45 µm and 0.22 µm acetate membranes, but the microfiltration membrane was not selective for the enrichment of organic matter. Thus, NF mainly enriched the fulvic acid and humic acid in urban sewage. The enrichment degree was 52.01% and 53.57%, respectively, and the total enrichment degree of dissolved organic matter was about 42%.

Anti-VEGFR2-interferon-α2 regulates the tumor microenvironment and exhibits potent antitumor efficacy against colorectal cancer.

Interferon-α (IFNα) has multiple antitumor effects including direct antitumor toxicity and the ability to potently stimulate both innate and adaptive immunity. However, its clinical applications in the treatment of malignancies have been limited because of short half-life and serious adverse reactions when attempting to deliver therapeutically effective doses. To address these issues, we fused IFNα2a to the anti-vascular endothelial growth factor and receptor 2 (VEGFR2) antibody JZA00 with the goal of targeting it to the tumor microenvironment where it can stimulate the antitumor immune response. The fusion protein, JZA01, is effective against colorectal cancer by inhibiting angiogenesis, exhibiting direct cytotoxicity, and activating the antitumor immune response. Although JZA01 exhibited reduced IFNα2 activity in vitro compared with native IFNα2, VEGFR2 targeting permitted efficient antiproliferative, proapoptotic, antiangiogenesis, and immune-stimulating effects against the colorectal tumors HCT-116 and SW620. JZA01 showed in vivo efficacy in NOD-SCID mice-bearing established HCT-116 tumors. In conclusion, this study describes an antitumor immunotherapy that is highly promising for the treatment of colorectal cancer.