Hyaluronic acid-coated porphyrin nanoplatform with oxygen sustained supplying and glutathione depletion for enhancing photodynamic/ion/chemo synergistic cancer treatment.

Hypoxia and high concentration of glutathione (GSH) in tumor seriously hinder the role of reactive oxygen species (ROS) and oxygen-dependence strategy in tumor treatment. In this work, a self-generating oxygen and self-consuming GSH hyaluronic acid (HA)-coated porphyrin nanoplatform (TAPPP@CaO2/Pt(IV)/HA) is established for enhancing photodynamic/ion/chemo targeting synergistic therapy of tumor. During the efforts of ROS production by nanosystems, a GSH consuming strategy is implemented for augmenting ROS-induced oxidative damage for synergetic cancer therapy. CaO2 in the nanosystems is decomposed into O2 and H2O2 in an acidic environment, which alleviates hypoxia and enhances the photodynamic therapy (PDT) effect. Calcium overload causes mitochondria dysfunction and induces apoptosis. Pt (IV) reacts with GSH to produce Pt (II) for chemotherapy and reduce the concentration of GSH, protecting ROS from scavenging for augmenting ROS-induced oxidative damage. In vitro and in vivo results demonstrated the self-generating oxygen and self-consuming GSH strategy can enhance ROS-dependent PDT coupled with ion/chemo synergistic therapy. The proposed strategy not only solves the long-term problem that hypoxia limits therapeutic effect of PDT, but also ameliorates the highly reducing environment of tumors. Thus the preparation of TAPPP@CaO2/Pt(IV)/HA provided a novel strategy for the effective combined therapy of cancers.

Inverse metabolic engineering based on metabonomics for efficient production of hydroxytyrosol by Saccharomyces cerevisiae.

Metabolic engineering provides a powerful approach to efficiently produce valuable compounds, with the aid of emerging gene editing tools and diverse metabolic regulation strategies. However, apart from the current known biochemical pathway information, a variety of unclear constraints commonly limited the optimization space of cell phenotype. Hydroxytyrosol is an important phenolic compound that serves various industries with prominent health-beneficial properties. In this study, the inverse metabolic engineering based on metabolome analysis was customized and implemented to disclose the hidden rate-limiting steps and thus to improve hydroxytyrosol production in Saccharomyces cerevisiae (S. cerevisiae). The potential rate-limiting steps involved three modules that were eliminated individually via reinforcing and balancing metabolic flow, optimizing cofactor supply, and weakening the competitive pathways. Ultimately, a 118.53 % improvement in hydroxytyrosol production (639.84 mg/L) was achieved by inverse metabolic engineering.

Association between estimated plasma volume status and acute kidney injury in patients who underwent coronary revascularization: A retrospective cohort study from the MIMIC-IV database.

BACKGROUND: Acute kidney injury (AKI) remains a common complication of coronary revascularization and increases poor outcomes in critically ill surgical patients. Compared to the plasma volume status (PVS), estimated plasma volume status (ePVS) has the advantages of being noninvasive and simple and has been shown to be associated with worse prognosis in patients undergoing coronary revascularization. This study was to evaluate the association of ePVS with the risk of AKI in patients who underwent coronary revascularization. METHODS: In this retrospective cohort study, data of patients who underwent coronary revascularization were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database (2008-2019). The outcome was the occurrence of AKI after ICU admission. The covariates were screened via the LASSO regression method. Univariate and multivariate Logistic regression models were performed to assess the association of ePVS and PVS and the odds of AKI in patients who underwent coronary revascularization, with results shown as odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses of age, surgery, and anticoagulation agents and sequential organ failure assessment (SOFA) score were performed to further explore the association of ePVS with AKI. RESULTS: A total of 3,961 patients who underwent coronary revascularization were included in this study, of whom 2,863 (72.28%) had AKI. The high ePVS was associated with the higher odds of AKI in patients who received coronary revascularization (OR = 1.06, 95%CI: 1.02-1.10), after adjusting for the covariates such as age, race, SAPS-II score, SOFA score, CCI, weight, heart rate, WBC, RDW-CV, PT, BUN, glucose, calcium, PH, PaO2, mechanical ventilation, vasopressors, and diuretic. Similar results were found in patients who underwent the CABG (OR = 1.07, 95%CI: 1.02-1.11), without anticoagulation agents use (OR = 1.07, 95%CI: 1.03-1.12) and with high SOFA score (OR = 1.10, 95%CI: 1.04-1.17). No relationship was found between PVS and the odds of AKI in patients who underwent the coronary revascularization. CONCLUSION: The ePVS may be a promising parameter to evaluate the risk of AKI in patients undergoing coronary revascularization, which provides a certain reference for the risk stratification management of ICU patients who underwent coronary revascularization.

Injectable Therapeutic Hydrogel with H2O2 Self-Supplying and GSH Consumption for Synergistic Chemodynamic/Low-Temperature Photothermal Inhibition of Postoperative Tumor Recurrence and Wound Infection.

Postoperative tumor recurrence and wound infection remain significant clinical challenges in surgery, often requiring adjuvant therapies. The combination treatment of photothermal therapy (PTT) and chemodynamic therapy (CDT) has proven to be effective in cancer treatment and wound infection. However, the hyperthermia during PTT increases the risk of normal tissue damage, severely impeding its application. Moreover, the efficacy of CDT is limited by insufficient hydrogen peroxide (H2O2) and excessive glutathione (GSH) levels at tumor or infection sites. Herein, an injectable and multifunctional CuO2@Au hydrogel system (CuO2@Au Gel) is developed for synergistic CDT and low-temperature PTT (LTPTT) to prevent tumor recurrence and bacterial wound infections. CuO2@Au Gel is constructed by embedding therapeutic CuO2@Au into low-melting point agarose hydrogel. In vitro and in vivo experiments confirm that the CuO2@Au in CuO2@Au Gel is capable of self-supplying H2O2 and depleting GSH, exhibiting effective CDT effect in acidic tumor or bacterial infected microenvironment. Additionally, it exhibits favorable photothermal conversion ability, inducing localized temperature elevation and synergistically enhancing CDT efficiency. The prepared CuO2@Au Gel demonstrates efficient tumor ablation capability in post-surgery recurrence mouse models and exhibits promising anti-infective efficiency in bacterial infection wound models, indicating significant potential in adjuvant therapy for post-surgical treatment and recovery.

Mesoporous polydopamine Targeting CDK4/6 Inhibitor toward Brilliant Synergistic Immunotherapy of Breast Cancer.

Immunotherapy utilizing anti-PD-L1 blockade has achieved dramatic success in clinical breast cancer management but is often hampered by the limited immune response. Increasing evidence shows that immunogenic cell death (ICD) recently arises as a promising strategy for enlarging tumor immunogenicity and eliciting systemic anti-tumor immunity effectively. However, developing simple but versatile, highly efficient but low-toxic, biosafe, and clinically available transformed ICD inducers remains a huge demand and is highly desirable. Herein, a multifunctional ICD inducer is purposefully developed A6-MPDA@PAL by integrating photothermal therapy (PTT) nanoplatforms mesoporous polydopamine (MPDA), CDK4/6 inhibitor palbociclib (PAL), and CD44-specific targeting A6 peptide in a simple way for augmenting the immune antitumor efficacy of anti-PD-L1 therapy. Remarkably, the light-inducible nanoplatforms exhibit multiple favorable therapeutic features ensuring a superior and biosafe PTT/chemotherapy efficacy. Together with stronger accumulative ICD induction, single administration of A6-MPDA@PAL can trigger robust systemic antitumor immunity and abscopal effect with the assistance of anti-PD-L1 blockade by fascinating the intratumoral infiltration of T lymphocytes and reversing the immunosuppressive tumor microenvironment simultaneously, therapy achieving brilliant synergistic immunotherapy with effective tumor ablation. This study presents a simple and smart ICD inducer opening up attractive clinical possibilities for reinforcing the anti-PD-L1 therapy against breast cancer.

Copper(II)-infused porphyrin MOF: maximum scavenging GSH for enhanced photodynamic disruption of bacterial biofilm.

Bacterial biofilm infection is a serious obstacle to clinical therapeutics. Photodynamic therapy (PDT) plays a dynamic role in combating biofilm infection by utilizing reactive oxygen species (ROS)-induced bacterial oxidation injury, showing advantages of mild side effects, spatiotemporal controllability and little drug resistance. However, superfluous glutathione (GSH) present in biofilm and bacteria corporately reduces ROS levels and seriously affects PDT efficiency. Herein, we have constructed a Cu2+-infused porphyrin metal-organic framework (MOF@Cu2+) for the enhanced photodynamic combating of biofilm infection by the maximum depletion of GSH. Our results show that the released Cu2+ from porphyrin MOF@Cu2+ could not only oxidize GSH in biofilm but also consume GSH leaked from ROS-destroyed bacteria, thus greatly weakening the antioxidant system in biofilm and bacteria and dramatically improving the ROS levels. As expected, our dual-enhanced PDT nanoplatform exhibits a strong biofilm eradication ability both in vitro and in an in vivo biofilm-infected mouse model. In addition, Cu2+ can promote biofilm-infected wound closing by provoking cell immigration, collagen sediment and angiogenesis. Besides, no apparent toxicity was detected after treatment with MOF@Cu2+. Overall, our design offers a new paradigm for photodynamic combating biofilm infection.

A nanozyme-reinforced injectable photodynamic hydrogel for combating biofilm infection.

Bacterial biofilm-associated infectious diseases remain serious menaces to human health. Recently, photodynamic therapy (PDT) has become a prospective strategy for combating biofilm infection. However, anaerobic conditions in a biofilm greatly inhibit its therapeutic efficacy. Here, a nanozyme-reinforced injectable hydrogel is prepared using Ca2+-crosslinked sodium alginate incorporated with photosensitizer-loaded MnO2 nanosheets and CaO2 nanoparticles for O2 self-sufficient PDT to eradicate biofilm infection. In our design, CaO2 reacts with water to produce locally concentrated H2O2, which could be catalyzed by MnO2 nanosheets (catalase-mimic nanozymes) to generate O2 and greatly relieve the hypoxic conditions in the biofilm, thus significantly strengthening PDT efficacy. In vitro assays confirmed that the hybrid hydrogel not only exhibits high-performance bactericidal activity in combating both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli but also shows great efficacy in eliminating biofilm infection. Moreover, benefiting from its good syringeability, the hybrid hydrogel is prone to fit irregular wounds and exhibits high efficiency in promoting wound healing in a biofilm-infected mice model. Besides, no obvious toxicity is detected in the hybrid hydrogel. Overall, we envision that our designed hydrogel could provide a prospective solution for combating biofilm-associated infections.

Investigating the Therapeutic Potential of Plants and Plant-Based Medicines: Relevance to Antioxidant and Neuroprotective Effects.

Oxidative stress is a common characteristic of psychiatric, neurological, and neurodegenerative disorders. Therefore, compounds that are neuroprotective and reduce oxidative stress may be of interest as novel therapeutics. Phenolic, flavonoid and anthocyanin content, ORAC and DPPH free radical scavenging, and Cu2+ and Fe2+ chelating capacities were examined in variations (fresh/capsule) of Queen Garnet plum (QGP, Prunus salicina), black pepper (Piper nigrum) clove (Syzygium aromaticum), elderberry (Sambucus nigra), lemon balm (Melissa officinalis) and sage (Salvia officinalis), plus two blends (Astralagus membranaceus-lemon balm-rich, WC and R8). The ability of samples to prevent and treat H2O2-induced oxidative stress in SH-SY5Y cells was investigated. Pre-treatment with WC, elderberry, QGP, and clove prevented the oxidative stress-induced reduction in cell viability, demonstrating a neuroprotective effect. Elderberry increased cell viability following oxidative stress induction, demonstrating treatment effects. Clove had the highest phenolic and flavonoid content, DPPH, and Cu2+ chelating capacities, whereas QGP and elderberry were highest in anthocyanins. Black pepper had the highest ORAC and Fe2+ chelating capacity. These findings demonstrate that plant extracts can prevent and treat oxidative stress-induced apoptosis of neuron-like cells in vitro. Further research into phytochemicals as novel therapeutics for oxidative stress in the brain is needed.

Wastewater-based epidemiology of Campylobacter spp.: A systematic review and meta-analysis of influent, effluent, and removal of wastewater treatment plants.

Campylobacter spp. is one of the four leading causes of diarrhoeal diseases worldwide, which are generally mild but can be fatal in children, the elderly, and immunosuppressed persons. The existing disease surveillance for Campylobacter infections is usually based on untimely clinical reports. Wastewater surveillance or wastewater-based epidemiology (WBE) has been developed for the early warning of disease outbreaks and the detection of the emerging new variants of human pathogens, especially after the global pandemic of COVID-19. However, the WBE monitoring of Campylobacter infections in communities is rare due to a few large data gaps. This study is a meta-analysis and systematic review of the prevalence of Campylobacter spp. in various wastewater samples, primarily the influent of wastewater treatment plants. The results showed that the overall prevalence of Campylobacter spp. was 53.26 % in influent wastewater and 52.97 % in all types of wastewater samples. The mean concentration in the influent was 3.31 ± 0.39 log10 gene copies or most probable number (MPN) per 100 mL. The detection method combining culture and PCR yielded the highest positive rate of 90.86 %, while RT-qPCR and qPCR were the two most frequently used quantification methods. In addition, the Campylobacter concentration in influent wastewater showed a seasonal fluctuation, with the highest concentration in the autumn at 3.46 ± 0.41 log10 gene copies or MPN per 100 mL. Based on the isolates of all positive samples, Campylobacter jejuni (62.34 %) was identified as the most prevalent species in wastewater, followed by Campylobacter coli (30.85 %) and Campylobacter lari (4.4 %). These findings provided significant data to further develop and optimize the wastewater surveillance of Campylobacter spp. infections. In addition, large data gaps were found in the decay of Campylobacter spp. in wastewater, indicating insufficient research on the persistence of Campylobacter spp. in wastewater.

Corrigendum: Fetoplacental transmission and placental response to SARS-CoV-2: evidence from the literature.

[This corrects the article DOI: 10.3389/fmed.2022.962937.].

Triplex qPCR assay for Campylobacter jejuni and Campylobacter coli monitoring in wastewater.

Campylobacter spp. is one of the most frequent pathogens of bacterial gastroenteritis recorded worldwide. Campylobacter jejuni (C. jejuni) and Campylobacter coli (C. coli) are the two major disease-associated species, accounting for >95 % of infections, and thus have been selected for disease surveillance. Monitoring temporal variations in pathogen concentration and diversity excreted from community wastewater allows the early detection of outbreaks. Multiplex real-time/quantitative PCR (qPCR) enables multi-target quantification of pathogens in various types of samples including wastewater. Also, an internal amplification control (IAC) is required for each sample when adopting PCR-based methods for pathogen detection and quantification in wastewater to exclude the inhibition of the wastewater matrix. To achieve reliable quantification of C. jejuni and C. coli towards wastewater samples, this study developed and optimized a triplex qPCR assay by combining three qPCR primer-probe sets targeting Campylobacter jejuni subsp. jejuni, Campylobacter coli, and Campylobacter sputorum biovar sputorum (C. sputorum), respectively. This triplex qPCR assay not only can directly and simultaneously detect the concentration of C. jejuni and C. coli in wastewater but also can achieve the PCR inhibition control using C. sputorum primer-probe set. This is the first developed triplex qPCR assay with IAC for C. jejuni and C. coli, to be used in the wastewater-based epidemiology (WBE) applications. The optimized triplex qPCR assay enables the detection limit of the assay (ALOD100%) and wastewater (PLOD80%) as 10 gene copy/µL and 2 log10 cells/mL (2 gene copies/µL of extracted DNA), respectively. The application of this triplex qPCR to 52 real raw wastewater samples from 13 wastewater treatment plants demonstrated its potential as a high-throughput and economically viable tool for the long-term monitoring of C. jejuni and C. coli prevalence in communities and the surrounding environments. This study provided an accessible methodology and a solid foundation for WBE-based monitoring of Campylobacter spp. relevant diseases and paved the road for future WBE back-estimation of C. jejuni and C. coli prevalence.

Healthy immigration effect among internal migrants in megacities: a cross-sectional study in Shanghai, China.

Objectives: To verify the healthy immigration effect on self-rated health (SRH) among Chinese internal migrants, identify the determinants of SRH, and provide recommendations for the Chinese government to formulate effective intervention strategies to improve population governance and health management in megacities. Methods: A sample comprising 1,147 white-and blue-collar migrant workers was randomly selected through an online survey conducted in Shanghai from August to December 2021. Multivariate logistic regression models were used to verify the healthy immigration effect as well as determinants of the effect among internal migrants in Shanghai. Results: Among 1,024 eligible internal migrants, 864 (84.4%) were aged between 18 and 59 years, 545 (53.2%) were men, and 818 (79.9%) were married. When confounders in the logistic regression models were adjusted, the odds ratio of SRH for internal migrants who had lived in Shanghai for 5-10 years was 2.418 (p < 0.001), whereas the odds ratio for those who had lived there for ≥10 years was not statistically significant. Additionally, marital status, a postgraduate or higher degree, income level, number of physical examinations in the past 12 months, and the number of critical diseases they were suffering from, were significant contributing factors for favorable SRH among the internal migrants. Furthermore, a cross-sectional analysis revealed that SRH demonstrated a healthy immigration effect among blue-collar internal migrants from the manufacturing industry but not among white-collar internal migrants. Conclusion: A healthy immigration effect was observed among internal migrants in Shanghai. The migrant population that had lived in Shanghai for 5-10 years had more health advantages than the locals, whereas those who had lived there for ≥10 years did not. The Chinese government should understand this effect and enact measures accordingly, such as implementing physical examinations, improving acculturation, addressing individual characteristics, and improving socioeconomic conditions to improve the physical and mental health of internal migrants. Enacting such changes could facilitate the integration of migrants into the local culture of megacities.

Elevated Interleukin-37 Associated with Dengue Viral Load in Patients with Dengue Fever.

Dengue remains a public health issue worldwide. Similar to chronic infectious diseases, stimulation of cytokine production is not enough to drive immune effector cells for effective virus clearance. One possible mechanism is the virus induces a large number of negative stimulatory cytokines inhibiting immune response. Interleukin 37 (IL-37) plays a crucial regulatory role in infection and immunity, inhibits innate and adaptive immunity as an anti-inflammatory cytokine by inhibiting proinflammatory mediators and pathways. To date, there are few studies reporting correlations between dengue fever (DF) and IL-37. In this study we found that the serum IL-37b and IL-37b-producing monocytes in patients were significantly increased in DF patients. A majority of the IL-37b produced by DF patients was produced by monocytes, not lymphocytes. Increased levels of IL-6, IL-10, and IFN-α were also found in DF patients. However, we failed to detect IL-1ß, IL-17A and TNF-α in plasma, because of off-target. In our study, there was no relation between IL-6, IL-10, and IFN-α expressions and IL-37b in serum (P > 0.05). The IL-37b-producing monocytes were negatively correlated with the level of IFN-α in serum and platelet count, and positively correlated with lymphocytes percentage (P < 0.05, respectively). Additionally, serum DENV nonstructural protein 1 levels were positively correlated with monocytes percentages (P < 0.05). Our data represents findings for IL-37b expression and its potential mechanisms in DF patients' immune response.

Association between acculturation and physician trust for internal migrants: A cross-sectional study in China.

BACKGROUND: Physician trust is a critical determinant of the physician-patient relationship and is necessary for an effective health system. Few studies have investigated the association between acculturation and physician trust. Thus, this study analyzed the association between acculturation and physician trust among internal migrants in China by using a cross-sectional research design. METHODS: Of the 2000 adult migrants selected using systematic sampling, 1330 participants were eligible. Among the eligible participants, 45.71% were female, and the mean age was 28.50 years old (standard deviation = 9.03). Multiple logistic regression was employed. RESULTS: Our findings indicated that acculturation was significantly associated with physician trust among migrants. The length of stay (LOS), the ability of speaking Shanghainese, and the integration into daily life were identified as contributing factors for physician trust when controlling for all the covariates in the model. CONCLUSION: We suggest that specific LOS-based targeted policies and culturally sensitive interventions can promote acculturation among Shanghai's migrants and improve their physician trust.

Photosensitive pro-drug nanoassemblies harboring a chemotherapeutic dormancy function potentiates cancer immunotherapy.

Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment. However, developing multifunctional biodegradable, biocompatible, low-toxic but highly efficient, and clinically available transformed nano-immunostimulants remains a challenge and is in great demand. Herein, we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid (BA), a water-soluble chitosan oligosaccharide (COS), and a low toxic photosensitizer chlorin e6 (Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy. We show that the designed nanodrugs harbored a smart and distinctive "dormancy" characteristic in chemotherapeutic effect with desired lower cytotoxicity, and multiple favorable therapeutic features including improved 1O2 generation induced by the reduced energy gap of Ce6, pH-responsiveness, good biodegradability, and biocompatibility, ensuring a highly efficient, synergistic photochemotherapy. Moreover, when combined with anti-PD-L1 therapy, both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy (PDT) could effectively activate antitumor immunity when treating primary or distant tumors, opening up potentially attractive possibilities for clinical immunotherapy.

Effects of sewer biofilms on the degradability of carbapenems in wastewater using laboratory scale bioreactors.

Carbapenems are last-resort antibiotics used to treat bacterial infections unsuccessfully treated by most common categories of antibiotics in humans. Most of their dosage is secreted unchanged as waste, thereby making its way into the urban water system. There are two major knowledge gaps addressed in this study to gain a better understanding of the effects of their residual concentrations on the environment and environmental microbiome: development of a UHPLC-MS/MS method of detection and quantification from raw domestic wastewater via direct injection and study of their stability in sewer environment during the transportation from domestic sewers to wastewater treatment plants. The UHPLC-MS/MS method was developed for four carbapenems: meropenem, doripenem, biapenem and ertapenem, and validation was performed in the range of 0.5-10 µg/L for all analytes, with limit of detection (LOD) and limit of quantification (LOQ) values ranging from 0.2-0.5 µg/L and 0.8-1.6 µg/L respectively. Laboratory scale rising main (RM) and gravity sewer (GS) bioreactors were employed to culture mature biofilms with real wastewater as the feed. Batch tests were conducted in RM and GS sewer bioreactors fed with carbapenem-spiked wastewater to evaluate the stability of carbapenems and compared against those in a control reactor (CTL) without sewer biofilms, over a duration of 12 h. Significantly higher degradation was observed for all carbapenems in RM and GS reactors (60 - 80%) as opposed to CTL reactor (5 - 15%), which indicates that sewer biofilms play a significant role in the degradation. First order kinetics model was applied to the concentration data along with Friedman's test and Dunn's multiple comparisons analysis to establish degradation patterns and differences in the degradation observed in sewer reactors. As per Friedman's test, there was a statistically significant difference in the degradation of carbapenems observed depending on the reactor type (p = 0.0017 - 0.0289). The results from Dunn's test indicate that the degradation in the CTL reactor was statistically different from that observed in either RM (p = 0.0033 - 0.1088) or GS (p = 0.0162 - 0.1088), with the latter two showing insignificant difference in the degradation rates observed (p = 0.2850 - 0.5930). The findings contribute to the understanding about the fate of carbapenems in urban wastewater and the potential application of wastewater-based epidemiology.

In-sewer decay and partitioning of Campylobacter jejuni and Campylobacter coli and implications for their wastewater surveillance.

Campylobacter jejuni and coli are two main pathogenic species inducing diarrhoeal diseases in humans, which are responsible for the loss of 33 million lives each year. Current Campylobacter infections are mainly monitored by clinical surveillance which is often limited to individuals seeking treatment, resulting in under-reporting of disease prevalence and untimely indicators of community outbreaks. Wastewater-based epidemiology (WBE) has been developed and employed for the wastewater surveillance of pathogenic viruses and bacteria. Monitoring the temporal changes of pathogen concentration in wastewater allows the early detection of disease outbreaks in a community. However, studies investigating the WBE back-estimation of Campylobacter spp. are rare. Essential factors including the analytical recovery efficiency, the decay rate, the effect of in-sewer transport, and the correlation between the wastewater concentration and the infections in communities are lacking to support wastewater surveillance. This study carried out experiments to investigate the recovery of Campylobacter jejuni and coli from wastewater and the decay under different simulated sewer reactor conditions. It was found that the recovery of Campylobacter spp. from wastewater varied with their concentrations in wastewater and depended on the detection limit of quantification methods. The concentration reduction of Campylobacter. jejuni and coli in sewers followed a two-phase reduction model, and the faster concentration reduction during the first phase is mainly due to their partitioning onto sewer biofilms. The total decay of Campylobacter. jejuni and coli varied in different types of sewer reactors, i.e. rising main vs. gravity sewer. In addition, the sensitivity analysis for WBE back-estimation of Campylobacter suggested that the first-phase decay rate constant (k1) and the turning time point (t1) are determining factors and their impacts increased with the hydraulic retention time of wastewater.

Predicting Persistent Acute Respiratory Failure in Acute Pancreatitis: The Accuracy of Two Lung Injury Indices.

BACKGROUND/AIMS: Early and accurate identification of patients with acute pancreatitis (AP) at high risk of persistent acute respiratory failure (PARF) is crucial. We sought to determine the accuracy of simplified Lung Injury Prediction Score (sLIPS) and simplified Early Acute Lung Injury (sEALI) for predicting PARF in ward AP patients. METHODS: Consecutive AP patients in a training cohort from West China Hospital of Sichuan University (n = 912) and a validation cohort from The First Affiliated Hospital of Nanchang University (n = 1033) were analyzed. PARF was defined as oxygen in arterial blood/fraction of inspired oxygen < 300 mmHg that lasts for > 48 h. The sLIPS was composed by shock (predisposing condition), alcohol abuse, obesity, high respiratory rate, low oxygen saturation, high oxygen requirement, hypoalbuminemia, and acidosis (risk modifiers). The sEALI was calculated from oxygen 2 to 6 L/min, oxygen > 6 L/min, and high respiratory rate. Both indices were calculated on admission. RESULTS: PARF developed in 16% (145/912) and 22% (228/1033) (22%) of the training and validation cohorts, respectively. In these patients, sLIPS and sEALI were significantly increased. sLIPS ≥ 2 predicted PARF in the training (AUROC 0.87, 95% CI 0.84-0.89) and validation (AUROC 0.81, 95% CI 0.78-0.83) cohorts. sLIPS was significantly more accurate than sEALI and current clinical scoring systems in both cohorts (all P < 0.05). CONCLUSIONS: Using routinely available clinical data, the sLIPS can accurately predict PARF in ward AP patients and outperforms the sEALI and current existing clinical scoring systems.

Constructing a self-healing injectable SABA/Borax/PDA@AgNPs hydrogel for synergistic low-temperature photothermal antibacterial therapy.

Infections caused by bacteria are one of the biggest challenges humans face around the world. Photothermal therapy (PTT) has been regarded as a promising strategy in combating pathogenic infection, however the high temperatures (55-65 °C) required during a single PTT process can induce injury to healthy tissues nearby. Combination therapy could overcome this problem by reducing the photothermal temperature. Here, we developed a self-healing and injectable hydrogel to realize low-temperature PTT (LT-PTT, ≤45 °C) for antisepsis with high-efficiency. The hybrid hydrogel is prepared by incorporating borax into a mixture of 3-aminophenylboronic acid grafted sodium alginate and nano-silver decorated polydopamine nanoparticles. Our results showed that the SABA/Borax/PDA@AgNPs hydrogel possesses satisfactory mechanical properties and self-healing capacity, and as a result, it can repair itself after being damaged mechanically, retaining its integrality and recovering its initial functionalities. Furthermore, through utilizing the photothermal property of polydopamine nanoparticles and broad-spectrum antibacterial activity of nano-silver, the hybrid hydrogel achieves excellent LT-PTT for sterilization both in vitro as well as in an in vivo mice skin wound model with no distinct injury to normal tissues. Overall, our prepared hydrogel is expected to be an excellent candidate for treating bacterial infections.

Fetoplacental transmission and placental response to SARS-CoV-2: Evidence from the literature.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a dreadful novel coronavirus with global health concerns among pregnant women. To date, the vertical transmission of SARS-CoV-2 during pregnancy remains controversial. We briefly report recent findings of placental response to SARS-CoV-2 infection and updates on vertical transmission. We systematically searched PubMed and Google Scholar databases according to PRISMA guidelines for studies reporting the effects of SARS-CoV-2 infection on the placenta and possibility of vertical transmission. We identified 45 studies reporting 1,280 human placentas that were analyzed by molecular pathology methods and 11,112 placenta-derived cells from a publicly available database that was analyzed using bioinformatics tools. The main finding of this study is that the SARS-CoV-2 canonical entry receptors (ACE2 and TMPRSS2) are abundantly expressed on the placenta during the first trimester, and this expression diminishes across gestational age. Out of 45 eligible studies identified, 24 (53.34%) showed no evidence of vertical transmission, 15 (33.33%) supported the hypothesis of very rare, low possibility of vertical transmission and 6 (13.33%) were indecisive and had no comment on vertical transmission. Furthermore, 433 placentas from 12 studies were also identified for placental pathology investigation. There was evidence of at least one form of maternal vascular malperfusion (MVM), 57/433 (13.1%), fetal vascular malperfusion (FVM), 81/433 (18.7%) and placental inflammation with excessive infiltration of CD3+ CD8+ lymphocytes, CD68+ macrophages and CD20+ lymphocytes in most of the eligible studies. Decidual vasculopathy (3.2%), infarction (3.2%), chronic histiocytic intervillositis (6.0%), thrombi vasculopathy (5.1%) were also observed in most of the MVM and FVM reported cases. The results indicated that SARS-CoV-2 induces placenta inflammation, and placenta susceptibility to SARS-CoV-2 decreases across the pregnancy window. Thus, SARS-CoV-2 infection in early pregnancy may adversely affect the developing fetus.