Enhanced multi-metals stabilization: Synergistic insights from hydroxyapatite and peroxide dosing strategies.

Sediment contamination by heavy metals is a pressing environmental concern. While in situ metal stabilization techniques have shown promise, a great challenge remains in the simultaneous immobilization of multi-metals co-existing in contaminated sediments. This study aims to address this challenge by developing a practical method for stabilizing multi-metals by hydroxyapatite and calcium peroxide (HAP/CaO2) dosing strategies. Results showed that dosing 15.12 g of HAP/CaO2 at a ratio of 3:1 effectively transformed labile metals into stable fractions, reaching reaction kinetic equilibrium within one month with a pseudo-second-order kinetic (R2 > 0.98). The stable fractions of Nickel (Ni), Chromium (Cr), and lead (Pb) increased by approximately 16.9 %, 26.7 %, and 21.9 %, respectively, reducing heavy metal mobility and ensuring leachable concentrations complied with the stringent environmental Class I standard. Mechanistic analysis indicated that HAP played a crucial role in Pb stabilization, exhibiting a high rate of 0.0176 d-1, while Cr and Ni stabilization primarily occurred through the formation of hydroxide precipitates, as well as the slowly elevated pH (>8.5). Importantly, the proposed strategy poses a minimal environmental risk to benthic organisms exhibits almost negligible toxicity towards Vibrio fischeri and the Chironomus riparius, and saves about 71 % of costs compared to kaolinite. These advantages suggest the feasibility of HAP/CaO2 dosing strategies in multi-metal stabilization in contaminated sediments.

Nomogram for predicting difficult total laparoscopic hysterectomy: A multi-institutional, retrospective model development and validation study.

BACKGROUND: Total laparoscopic hysterectomy (TLH) is the most commonly performed gynecological surgery. However, the difficulty of the operation varies depending on the patient and surgeon. Subsequently, patient's outcomes and surgical efficiency are affected. We aimed to develop and validate a pre-operative nomogram to predict the operative difficulty in patients undergoing TLH. METHODS: This retrospective study included 663 patients with TLH from XXX Hospital and 102 patients from YYY Hospital in Chongqing, China. A multivariate logistic regression analysis was used to identify the independent predictors of operative difficulty, and a nomogram was constructed. The performance of the nomogram was validated internally and externally. RESULTS: The uterine weight, history of pelvic surgery, presence of adenomyosis, surgeon's years of practice, and annual hysterectomy volume were identified as significant independent predictors of operative difficulty. The nomogram demonstrated good discrimination in the training dataset (area under the receiver operating characteristic curve [AUC], 0.827 (95% confidence interval [CI], 0.783-0.872), internal validation dataset (AUC, 0.793 [95% CI, 0.714-0.872]), and external validation dataset (AUC, 0.756 [95% CI, 0.658-0.854]). The calibration curves showed good agreement between the predictions and observations for both internal and external validations. CONCLUSION: The developed nomogram accurately predicted the operative difficulty of TLH, facilitated pre-operative planning and patient counseling, and optimized surgical training. Further prospective multicenter clinical studies are required to optimize and validate this model.

Application of calcium peroxide in promoting resource recovery from municipal sludge: A review.

The harmless disposal, resource recovery, and synergistic efficiency reduction of municipal sludge have been the research focuses for the last few years. Calcium peroxide (CaO2) is a multifunctional and safe peroxide that produces an alkaline oxidation environment to promote the fermentation of municipal sludge to produce hydrogen (H2) and volatile fatty acids (VFAs), thus realizing sludge resource recovery. This review outlines the research achievements of CaO2 in sludge resource recovery, improvement of sludge dewaterability, and removal of pollutants from sludge in recent years. Meanwhile, the mechanism of CaO2 and its influencing factors have also been comprehensively summarized. Finally, the future development direction of the application of CaO2 in municipal sludge is prospected. This review would provide theoretical reference for the potential engineering applications of CaO2 in improving sludge treatment in the future.

Insight into sludge dewatering by periodate driven directly with Fe(â ¡): Extracellular polymeric substances solubilization and mineralization.

The production of waste activated sludge is expanding in tandem with the significant growth in the global population. It is important to explore sludge pretreatment technology to achieve sludge reduction. In this study, deep sludge dewatering was achieved by using Fe2+-catalyzed periodate (Fe2+/PI) conditioning. The result showed that capillary suction time was reduced by 48.27% under the optimum Fe2+ and PI dosages. ·OH, FeⅣ, O2·-, 1O2, and IO3· generated from the reaction between Fe2+ and PI, while ·OH (49.79%) and FeⅣ (47.76%) contributed significantly to sludge dewatering. Investigations of the mechanism revealed that the synergistic action of radical species oxidation and iron species flocculation in Fe2+/PI conditioning led to the mineralization and aggregation of hydrophilic substances in extracellular polymeric substances. The hydrophobic groups on the protein surface were more exposed to soluble extracellular polymeric substances and reduced protein-water interaction. The variations in zeta potential and particle size also verified the presence of a synergistic effect of oxidation and flocculation. The morphology observations revealed that the increased frictional forces generated when water flowed over the raw sludge (RS) surface prevented the rapid passage of internal water. In addition, the hydrophobic and electrostatic interactions in the sludge samples were essential influences that promoted flocculation and sedimentation of the sludge. This research aids engineers by providing a new option to better optimize sludge management while also deepening understanding of the Fe2+/PI conditioning involved in sludge dewatering.

N6-methyladenosine modified LINC00901 promotes pancreatic cancer progression through IGF2BP2/MYC axis.

Accumulating evidence indicates that RNA methylation at N6-methyladenosine (m6A) plays an important regulatory role in gene expression and aberrant mRNA m6A modification is often associated with a variety of cancers. However, little is known whether and how m6A-modification impacts long non-coding RNA (lncRNA) and lncRNA-mediated tumorigenesis, particularly in pancreatic ductal adenocarcinoma (PDAC). In the present study, we report that a previously uncharacterized lncRNA, LINC00901, promotes pancreatic cancer cell growth and invasion and moreover, LINC00901 is subject to m6A modification which regulates its expression. In this regard, YTHDF1 serves as a reader for the m6A modified LINC00901 and downregulates the LINC00901 level. Notably, two conserved m6A sites in LINC00901 are critical to the recognition of LINC00901 by YTHDF1. Finally, RNA sequencing (RNA-seq) and gene function analysis revealed that LINC00901 positively regulates MYC through upregulation of IGF2BP2, a known RNA binding protein that can enhance MYC mRNA stability. Together, our results suggest that there is a LINC00901-IGF2BP2-MYC axis through which LINC00901 promotes PDAC progression in an m6A dependent manner.

A parylene-mediated plasmonic-photonic hybrid fiber-optic sensor and its instrumentation for miniaturized and self-referenced biosensing.

With the development of advanced nanofabrication techniques over the past decades, different nanostructure-based plasmonic fiber-optic sensors have been developed and have presented a low limit of detection for various biomolecules. However, owing to both the dependence on complex equipment and the trade-off between the fabrication cost and sensing performance, nanostructured plasmonic fiber-optic sensors are rarely used outside laboratories. To facilitate wider application of the plasmonic fiber-optic sensors, a parylene-mediated hybrid plasmonic-photonic cavity-based sensor was developed. Compared with a similar plasmonic sensor which only works in the plasmonic mode, the proposed hybrid sensor shows a higher reproducibility (CV < 2.5%) due to its resistance to fabrication variations. Meanwhile, a self-referenced detection mechanism and a novel miniaturized system were developed to adapt to the hybrid resonance sensor. The entire system only has a weight of 263 g, and a size of 12 cm × 10 cm × 8 cm, and is especially suitable for outdoor applications in a handheld manner. In experiments, a high refractive index sensitivity of 3.148 RIU-1 and real-time biomolecule monitoring at nanomolar concentrations were achieved by the proposed system, further confirming the potential of the miniaturized system as a candidate for point-of-care health diagnostics outside laboratories.

From the teapot effect to tap-triggered self-wetting: a 3D self-driving sieve for whole blood filtration.

Achieving passive microparticle filtration with micropore membranes is challenging due to the capillary pinning effect of the membranes. Inspired by the teapot effect that occurs when liquid (tea) is poured from a teapot spout, we proposed a tap-triggered self-wetting strategy and utilized the method with a 3D sieve to filter rare cells. First, a 3D-printed polymer tap-trigger microstructure was implemented. As a result, the 3 µm micropore membrane gating threshold (the pressure needed to open the micropores) was lowered from above 3000 to 80 Pa by the tap-trigger microstructure that facilated the liquid leakage and spreading to self-wet more membrane area in a positive feedback loop. Then, we implemented a 3D cone-shaped cell sieve with tap-trigger microstructures. Driven by gravity, the sieve performed at a high throughput above 20 mL/min (DPBS), while the micropore size and porosity were 3 µm and 14.1%, respectively. We further filtered leukocytes from whole blood samples with the proposed new 3D sieve, and the method was compared with the traditional method of leukocyte isolation by chemically removing red blood cells. The device exhibited comparable leukocyte purity but a higher platelet removal rate and lower leukocyte simulation level, facilitating downstream single-cell analysis. The key results indicated that the tap-triggered self-wetting strategy could significantly improve the performance of passive microparticle filtration.

Brachial-Ankle Pulse Wave Velocity Mediates the Association between Increased Age and Risk of Sarcopenia among Chinese Patients with Type 2 Diabetes Mellitus.

Background and Aims: Arterial stiffness and sarcopenia are commonly seen in patients with type 2 diabetes mellitus (T2DM), and both are age-related diseases. However, few studies have addressed the causal relationship between age, arterial stiffness, and sarcopenia, especially in patients with T2DM. This study is aimed at investigating the relationship among age, arterial stiffness, and sarcopenia in patients with T2DM. Methods and Results: This cross-sectional study enrolled 557 inpatients with diabetes at the First Affiliated Hospital of Wenzhou Medical University, China, between June 2020 and July 2021. Patients who were diagnosed with T2DM and underwent examination of dual-energy X-ray absorptiometry, handgrip strength, 6-meter walk speed, and brachial-ankle pulse wave velocity (baPWV, a recognized indicator of arterial stiffness) were enrolled. A total of 447 patients were included. A dose-dependent relationship was found between age and sarcopenia. We also found a dose-dependent relationship between age and baPWV. Similarly, significant dose-dependent relationships were found across baPWV tertiles with higher prevalence of sarcopenia. Then, a mediation analysis was performed to explore the mediation effect of arterial stiffness on age-associated sarcopenia. We found that the prevalence of sarcopenia increased by 0.0115 (95% CI, 0.0028-0.0239) per 1 year increase in age by the mediation effect of baPWV and that the direct effect of aging on sarcopenia was 0.0441 (95% CI, 0.0101-0.0909) per 1 year older. baPWV mediated 20.5% of the positive relationship between increased age and the prevalence of sarcopenia. Conclusions: Elevated baPWV partially mediates the association of age and sarcopenia among patients with T2DM.

Comparing SARC-CalF With SARC-F for Screening Sarcopenia in Adults With Type 2 Diabetes Mellitus.

Background: The prevalence of sarcopenia is high in older people with type 2 diabetes mellitus (T2DM) and is now considered a critical problem in the healthcare sector. However, the preferred screening tool for identifying sarcopenia remains unknown. Thus, the aim of this study was to ensure that the diagnostic values of the SARC-F (strength, assisting with walking, rising from a chair, climbing stairs, and falling) and SARC-CalF (SARC and calf circumference) scales were compared with five reference diagnostic criteria for sarcopenia. Methods: This was a cross-sectional study. Patients diagnosed with diabetes were treated at the First Affiliated Hospital of Wenzhou Medical University. Appendicular skeletal muscle mass, muscle strength, and physical performance were assessed using dual-energy X-ray absorptiometry, handgrip strength, and gait speed assessment. Five diagnostic criteria for sarcopenia (Asian Working Group for Sarcopenia, International Working Group on Sarcopenia, Foundation for the National Institutes of Health, Sarcopenia Project, Society on Sarcopenia Cachexia and Wasting Disorders, and European Working Group on Sarcopenia in Older People criteria) were utilized. Sensitivity and specificity analyses were performed on the SARC-CalF and SARC-F scales. The diagnostic precision of both instruments was determined using the receiver-operating characteristic (ROC) curves and area under the ROC curves (AUC). Results: This study included 689 subjects (459 men and 230 women) with a mean age of 58.1 ± 13.2 years. In accordance with the five reference diagnostic parameters, the prevalence of sarcopenia was between 4.5 and 19.2%. In addition, the range of sensitivity of SARC-F and SARC-CalF ranged from 61.4 to 67.4 and 82.6 to 91.8%, respectively. Concurrently, the specificity ranged from 63.1 to 67.3 and 51.5 to 61.2%, respectively. Overall, AUC values for SARC-CalF were higher than those for SARC-F, regardless of the diagnostic standard, sex, or age. Conclusion: The results of this study suggest that SARC-CalF significantly enhances the sensitivity and overall diagnosis of SARC-F. SARC-CalF appears to be an optimal screening tool for sarcopenia in adults with T2DM.

Recent Progress of Research Regarding the Applications of Stem Cells for Treating Diabetes Mellitus.

At present, the number of diabetes patients has exceeded 537 million worldwide and this number continues to increase. Stem cell therapy represents a new direction for the treatment of diabetes; the use of stem cells overcomes some shortcomings associated with traditional therapies. Functional ß cells play an important role in the pathogenesis of diabetes. As therapeutic targets, functional ß cells are restored by a variety of stem cells, including pluripotent stem cells, mesenchymal cells, and urine-derived stem cells. Although all types of stem cells have their own characteristics, they mainly promote the repair and regeneration of ß cells through directional differentiation, immunomodulation, and paracrine signaling after homing to the injured site. However, stem cell therapy still faces many obstacles, such as low long-term cell survival rate after transplantation, low maintenance time of blood glucose homeostasis, immune rejection, and tumorigenesis. Recently, genetically edited pluripotent stem cells and the cotransplantation of mesenchymal stem cells and islet cells have made significant progress in improving the efficacy of stem cell transplantation processes, also providing powerful tools for the study of the mechanisms underlying diabetes and disease modeling. In this review, we first focused on: (1) stem cells as a pool for the differentiation of insulin-producing cells; (2) stem cells as a source for regenerative repair of damaged islets and as a potential cotransplanted population with islets; (3) the potential of combining gene editing with stem cell therapy; and (4) selection of the stem cell transplantation approach. Based on these topics, we discuss the challenges within the field of adapting stem cell-supported and stem cell-derived transplantations and the promising routes for overcoming these problems.

A 3D Capillary-Driven Multi-Micropore Membrane-Based Trigger Valve for Multi-Step Biochemical Reaction.

Point-of-care testing (POCT) techniques based on microfluidic devices enabled rapid and accurate tests on-site, playing an increasingly important role in public health. As the critical component of capillary-driven microfluidic devices for POCT use, the capillary microfluidic valve could schedule multi-step biochemical operations, potentially being used for broader complex POCT tasks. However, owing to the reciprocal relationship between the capillary force and aperture in single-pore microchannels, it was challenging to achieve a high gating threshold and high operable liquid volume simultaneously with existing 2D capillary trigger valves. This paper proposed a 3D capillary-driven multi-microporous membrane-based trigger valve to address the issue. Taking advantage of the high gating threshold determined by micropores and the self-driven capillary channel, a 3D trigger valve composed of a microporous membrane for valving and a wedge-shaped capillary channel for flow pumping was implemented. Utilizing the capillary pinning effect of the multi-micropore membrane, the liquid above the membrane could be triggered by putting the drainage agent into the wedge-shaped capillary channel to wet the underside of the membrane, and it could also be cut off by taking away the agent. After theoretical analysis and performance characterizations, the 3D trigger valve performed a high gating threshold (above 1000 Pa) and high trigger efficiency with an operable liquid volume above 150 µL and a trigger-to-drain time below 6 s. Furthermore, the retention and trigger states of the valve could be switched for repeatable triggering for three cycles within 5 min. Finally, the microbead-based immunoreaction and live cell staining applications verified the valve's ability to perform multi-step operations. The above results showed that the proposed 3D trigger valve could be expected to play a part in wide-ranging POCT application scenarios.

Refractory hypokalemia caused by cetuximab with advanced colorectal cancer patients: the case series and literature review.

Cetuximab is the first-line treatment for advanced metastatic colon cancer. But cetuximab can cause electrolyte disturbances, including hypomagnesemia and hypokalemia. Among them, hypokalemia is often caused by hypomagnesemia, not directly caused by cetuximab. This article reports two cases of refractory hypokalemia caused by cetuximab without hypomagnesemia. The two patients had no abnormalities in serum potassium before cetuximab treatment. The occurrence of hypokalemia was clearly correlated with the cetuximab, and they were significantly improved after stopping or reducing the dose. At the same time, the appearance of hypokalemia is significantly related to the efficacy of cetuximab. They have received 37 and 35 cycles of cetuximab-related therapy, with condition stable periods of 12.8 and 15.1 months, respectively. Obviously, our report refutes the above view. In our opinion, hypokalemia, a side effect of cetuximab, may be directly caused by it, rather than secondary to hypomagnesemia. Similar to hypomagnesemia, the appearance of hypokalemia often indicates a better curative effect of cetuximab.

A simple model predicting in-hospital death in patients with type A acute aortic dissection.

BACKGROUND: Type A acute aortic dissection (TAAAD) is a destructive cardiovascular disease, with high morbidity and mortality rates. Identifying the high-risk TAAAD patients at an early stage is urgently necessary. METHODS: A retrospective study of 160 patients was carried out. The admission data were retrospectively gathered. Logistic regression analysis and receiver operator characteristic curve (AUC) was utilized. RESULTS: Compared with the survivor group, the nonsurvivor group was older, had higher D-dimer levels, red blood cell distribution width (RDW) levels and platelet distribution width (PDW) levels, and lower fibrinogen levels, platelet levels and plateletcrit levels. Multivariate analysis displayed that four independent factors, age (hazard ratio (HR): 7.877, 95% confidence interval (CI) 2.740-22.641, p < 0.001), D-dimer (HR: 3.791, 95% CI 1.520-9.452, p = 0.004), RDW (HR: 3.300, 95% CI 1.109-9.825, p = 0.032), PDW (HR: 3.755, 95% CI 1.436-9.815, p = 0.007) were incorporated into the model. The predict accuracy of the model (AUC 0.861, 95% CI 0.798-0.911, p < 0.001) was best. CONCLUSIONS: Age, D-dimer, RDW and PDW are independent markers of in-hospital death in TAAAD patients and the newly established model has better performance in predicting high-risk patients. This model can be used as a quick screening tool to assess the prognosis of patients in individualizing.

Genomic Landscape in Neoplasm-Like Stroma Reveals Distinct Prognostic Subtypes of Pancreatic Ductal Adenocarcinoma.

As a main component of the tumor microenvironment, the stroma is critical in development, progression, and metastasis of pancreatic ductal adenocarcinoma (PDAC). The genomic status and its relationship of neoplastic and stromal components remain unclear in PDAC. We performed targeted sequencing for 1,021 cancer-suspected genes on parallel microdissected stromal and neoplastic components from 50 operable PDAC patients. Clonality analysis of mutations was conducted to reconstruct the evolutionary trajectory, and then molecular subtypes were established. Multi-lineage differentiation potential and mesenchymal transformation of KRAS-mutant cell line Panc1 were evaluated using RT-PCR and immunofluorescence staining. In this study, 39 (78.0%) were genomically altered in stroma, with KRAS (71.8%), TP53 (61.5%), and CDKN2A (23.1%) as the most commonly mutated genes. The majority of stromal mutations (89.8%) were detected in matched neoplastic components. Patients with KRAS/TP53-mut stroma demonstrated a higher tumor cell fraction (TCF) than did those with wild-type (WT) stroma (p = 0.0371, p = 0.0014). In both components, mutants KRAS and TP53 often occurred as clonal events, and the allele frequencies presented linear correlation in the same specimen. All neoplasm-like stroma (characterized with all or initial neoplastic clones and driver events in stroma) harbored KRAS or TP53 mutations. Neoplasm-like and KRAS-mutant stroma was associated with shorter disease-free survival. It is a new finding for the existence of driver gene mutations in PDAC stroma. These data suggest that genomic features of stromal components may serve as prognostic biomarkers in resectable PDAC and might help to guide a more precise treatment paradigm in therapeutic options.

Lnc-DC promotes estrogen independent growth and tamoxifen resistance in breast cancer.

Selective estrogen receptor modulators (SERMs) such as tamoxifen have proven to be effective in the treatment of estrogen receptor (ER) positive breast cancer. However, a major obstacle for such endocrine therapy is estrogen independent growth, leading to resistance, and the underlying mechanism is not fully understood. The purpose of this study was to determine whether long non-coding RNAs (lncRNAs) are involved in regulation of estrogen independent growth and tamoxifen resistance in ER positive breast cancer. Using a CRISPR/Cas9-based SAM (synergistic activation mediator) library against a focus group of lncRNAs, we identify Lnc-DC as a candidate lncRNA. Further analysis suggests that Lnc-DC is able to reduce tamoxifen-induced apoptosis by upregulation of anti-apoptotic genes such as Bcl2 and Bcl-xL. Furthermore, Lnc-DC activates STAT3 by phosphorylation (pSTAT3Y705), and the activated STAT3 subsequently induces expression of cytokines which in turn activate STAT3, forming an autocrine loop. Clinically, upregulation of Lnc-DC is associated with poor prognosis. In particular, analysis of a tamoxifen-treated patient cohort indicates that Lnc-DC expression can predict the response to tamoxifen. Together, this study demonstrates a previously uncharacterized function of Lnc-DC/STAT3/cytokine axis in estrogen independent growth and tamoxifen resistance, and Lnc-DC may serve as a potential predictor for tamoxifen response.

Role of mean platelet volume in differential diagnosis of adult-onset Still's disease and sepsis

SUMMARY OBJECTIVES: Mean platelet volume is a simple biomarker for inflammatory disease. The purpose of this study is to evaluate the role of mean platelet volume in distinguishing adult-onset Still's disease from sepsis. METHODS: We retrospectively selected 68 patients with adult-onset Still's disease and 55 patients with sepsis between January 2015 and December 2019. Related laboratory data were collected and analyzed. RESULTS: There were no significant differences in white blood cell counts, neutrophils, lymphocytes, and C-reactive protein between adult-onset Still's disease group and sepsis group. However, patients in adult-onset Still's disease group showed higher ferritin and platelets and lower mean platelet volume and platelet distribution width than those in sepsis group (p<0.01 for both). Receiver operating characteristic curve analysis was performed to distinguish adult-onset Still's disease and sepsis. The area under the curve of mean platelet volume was 0.761 (95%CI 0.673-0.849), with a sensitivity of 79.1%, a specificity of 63.3%, and a cutoff value of 10.9 fL. In contrast, the area under the curve of combined ferritin and mean platelet volume was 0.90l (95%CI 0.837-0.965), with higher sensitivity (82.8%) and specificity (96.2%). Therefore, mean platelet volume could be used as a supplementary indicator to distinguish adult-onset Still's disease from sepsis. CONCLUSION: We suggest that mean platelet volume could be used as a supplementary biomarker for differential diagnosis of adult-onset Still's disease and sepsis in addition to ferritin.

A Neoantigen-Based Peptide Vaccine for Patients With Advanced Pancreatic Cancer Refractory to Standard Treatment.

Background: Neoantigens are critical targets to elicit robust antitumor T-cell responses. Personalized cancer vaccines developed based on neoantigens have shown promising results by prolonging cancer patients' overall survival (OS) for several cancer types. However, the safety and efficacy of these vaccine modalities remains unclear in pancreatic cancer patients. Methods: This retrospective study enrolled 7 advanced pancreatic cancer patients. Up to 20 neoantigen peptides per patient identified by our in-house pipeline iNeo-Suite were selected, manufactured and administered to these patients with low tumor mutation burden (TMB) (less than 10 mutations/Mb). Each patient received multiple doses of vaccine depending on the progression of the disease. Peripheral blood samples of each patient were collected pre- and post-vaccination for the analysis of the immunogenicity of iNeo-Vac-P01 through ELISpot assay and flow cytometry. Results: No severe vaccine-related adverse effects were witnessed in patients enrolled in this study. The mean OS, OS associated with vaccine treatment and progression free survival (PFS) were reported to be 24.1, 8.3 and 3.1 months, respectively. Higher peripheral IFN-γ titer and CD4+ or CD8+ effector memory T cells count post vaccination were found in patients with relatively long overall survival. Remarkably, for patient P01 who had a 21-month OS associated with vaccine treatment, the abundance of antigen-specific TCR clone drastically increased from 0% to nearly 100%, indicating the potential of iNeo-Vac-P01 in inducing the activation of a specific subset of T cells to kill cancer cells. Conclusions: Neoantigen identification and selection were successfully applied to advanced pancreatic cancer patients with low TMB. As one of the earliest studies that addressed an issue in treating pancreatic cancer with personalized vaccines, it has been demonstrated that iNeo-Vac-P01, a personalized neoantigen-based peptide vaccine, could improve the currently limited clinical efficacy of pancreatic cancer. Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT03645148).Registered August 24, 2018 - Retrospectively registered.

Management and Thinking on the Treatment of Cancer Patients During the COVID-19.

Coronavirus disease-2019 (COVID-19) has spread rapidly around the world and has become a public health emergency of international concern. The weekly epidemiological report issued by the WHO pointed out that new coronavirus variants have appeared in 131 countries and regions, which demonstrates that the current epidemic situation is still severe. As of now, the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been widespread worldwide for more than one year and poses a serious threat to the health of vulnerable groups such as those with malignancies, the elderly, and the immunocompromised. Compared with the general population, cancer patients with COVID-19 infection are more likely to have serious clinical adverse events, leading to higher mortality. There is no doubt that during the COVID-19 epidemic, whether it is with regards to how to prevent infection or how to continue anti-tumor treatment, cancer patients are in a difficult situation. Meanwhile, an international patient with malignant Hodgkin's lymphoma who was cured after being infected with the new coronavirus surprised us, and it inspires more scientists to explore the relationship between infection, immunity, and tumors. Relevantly, through multi-disciplinary discussion, scientists put forward more new perspectives on the treatment of future tumors and the management of SARS-CoV-2 diseases. In this review, the impact of COVID-19 on cancer patients is discussed in detail and the recommendations for the diagnosis, treatment and management of cancer patients will be put forward under the challenge of the COVID-19 epidemic. Furthermore, the safety and effectiveness of the SARS-CoV-2 vaccine will be discussed, and we will also put forward our insights on cancer immunity.

C-peptide ameliorates high glucose-induced podocyte dysfunction through the regulation of the Notch and TGF-ß signaling pathways.

The podocyte is one of the main components of the glomerular filtration barrier in the kidney, and its injury may contribute to proteinuria, glomerulosclerosis and eventually kidney failure. C-peptide, a cleavage product of proinsulin, shows therapeutic potential for treating diabetic nephropathy (DN). The aim of this study was to investigate the effect of C-peptide on high glucose-induced podocyte dysfunction. In the present study, we found that the protective effects of islet transplantation were superior to simple insulin therapy for the treatment of DN in streptozotocin (STZ)-treated rats. And such superiority may due to the function of C-peptide secreted at the implanted site. Based on this background, we determined that the application of C-peptide significantly prevented high glucose-induced podocyte injury by increasing the expression of nephrin and synaptopodin. Meanwhile, C-peptide suppressed high glucose-induced epithelial-mesenchymal transition (EMT) and renal fibrosis via decreasing the expression of snail, vimentin, α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF). Moreover, the Notch and transforming growth factor-ß (TGF-ß) signaling pathways were activated by high glucose, and treatment with C-peptide down-regulated the expression of the Notch signaling molecules Notch 1 and Jagged 1 and the TGF-ß signaling molecule TGF-ß1. These findings suggested that C-peptide might serve as a novel treatment method for DN and podocyte dysfunction.

Reduction-Responsive Anticancer Nanodrug Using a Full Poly(ethylene glycol) Carrier.

Poly(ethylene glycol) (PEG) is applied extensively in biomedical fields because of its nontoxic, nonimmunogenic, and protein resistance properties. However, the strong hydrophilicity of PEG prevents it from self-assembling into an amphiphilic micelle in water, making it a challenge to fabricate a full-PEG carrier to deliver hydrophobic anticancer drugs. Herein, a paclitaxel (PTX)-loaded nanodrug was readily prepared through self-assembly of PTX and an amphiphilic PEG derivative, which was synthesized via melt polycondensation of two PEG diols (i.e., PEG200 and PEG10k) and mercaptosuccinic acid. The full PEG component endows the nanocarrier with good biocompatibility. Furthermore, because of the core cross-linked structure via the oxidation of mercapto groups, the nanodrug can be selectively disassociated under an intratumor reductive microenvironment through the reduction of disulfide bonds to release the loaded PTX and kill the cancer cells while maintaining high stability under the extratumor physiological condition. Additionally, it was confirmed that the nanodrug not only prolongs the biocirculation time of PTX but also possesses excellent in vivo antitumor efficacy while avoiding side effects of free PTX, for example, liver damage, which is promising for delivering clinical hydrophobic drugs to treat a variety of malignant tumors.