Risk assessment and classification prediction for water environment treatment PPP projects.

Water treatment public-private partnership (PPP) projects are pivotal for sustainable water management but are often challenged by complex risk factors. Efficient risk management in these projects is crucial, yet traditional methodologies often fall short of addressing the dynamic and intricate nature of these risks. Addressing this gap, this comprehensive study introduces an advanced risk classification prediction model tailored for water treatment PPP projects, aimed at enhancing risk management capabilities. The proposed model encompasses an intricate evaluation of crucial risk areas: the natural and ecological environments, socio-economic factors, and engineering entities. It delves into the complex relationships between these risk elements and the overall risk profile of projects. Grounded in a sophisticated ensemble learning framework employing stacking, our model is further refined through a weighted voting mechanism, significantly elevating its predictive accuracy. Rigorous validation using data from the Jiujiang City water environment system project Phase I confirms the model's superiority over standard machine learning models. The development of this model marks a significant stride in risk classification for water treatment PPP projects, offering a powerful tool for enhancing risk management practices. Beyond accurately predicting project risks, this model also aids in developing effective government risk management strategies.

Lateral single incision laparoscopic totally extraperitoneal hernioplasty (L-SILTEP) after laparoscopic radical prostatectomy: A rare case report with literature review.

INTRODUCTION: Single-incision laparoscopic totally extraperitoneal hernioplasty is a commonly used surgical procedure for the treatment of inguinal hernia. However, it is difficult to use traditional single incision laparoscopic totally extraperitoneal hernioplasty to treat inguinal hernia after laparoscopic radical prostatectomy. We successfully and smoothly cured a patient with left inguinal hernia after laparoscopic radical prostatectomy using lateral single incision laparoscopic totally extraperitoneal hernioplasty. CASE PRESENTATION: We report the case of a 70-year-old man who underwent laparoscopic radical prostatectomy 2 years earlier and had an evanescent mass in the left inguinal region for 1 month. DIAGNOSIS: On the basis of preoperative abdominal computed tomography and intraoperative findings, the patient was diagnosed with a left indirect inguinal hernia, and post-laparoscopic radical prostatectomy. INTERVENTIONS: The patient underwent lateral single incision laparoscopic totally extraperitoneal hernioplasty. OUTCOMES: The patient recovered well after the operation, and there were no postoperative complications or recurrence of inguinal hernia 3 months after the operation. CONCLUSION: For patients who have undergone laparoscopic radical prostatectomy, lateral single-incision laparoscopic totally extraperitoneal hernioplastycan be performed.

Selection of HBV key reactivation factors based on maximum information coefficient combined with cosine similarity.

BACKGROUND: Hepatitis B Virus (HBV) reactivation is the most common complication for patients with primary liver cancer (PLC) after radiotherapy. How to reduce the reactivation of HBV has been a hot topic in the study of postoperative radiotherapy for liver cancer. OBJECTIVE: To find out the inducement of HBV reactivation, a feature selection algorithm (MIC-CS) using maximum information coefficient (MIC) combined with cosine similarity (CS) was proposed to screen the risk factors that may affect HBV reactivation. METHOD: Firstly, different factors were coded and MIC between patients was calculated to acquire the association between different factors and HBV reactivation. Secondly, a cosine similarity algorithm was constructed to calculate the similarity relationship between different factors, thus removing redundant information. Finally, combined with the weight of the two, the potential risk factors were sorted and the key factors leading to HBV reactivation were selected. RESULTS: The results indicated that HBV baseline, external boundary, TNM, KPS score, VD, AFP, and Child-Pugh could lead to HBV reactivation after radiotherapy. The classification model was constructed for the above factors, with the highest classification accuracy of 84% and the AUC value of 0.71. CONCLUSION: Comparing multiple feature selection methods, the results showed that the effect of the MIC-CS was significantly better than MIM, CMIM, and mRMR, so it has a very broad application prospect.

Sustained viremia suppression by SHIVSF162P3CN-recalled effector-memory CD8+ T cells after PD1-based vaccination.

HIV-1 functional cure requires sustained viral suppression without antiretroviral therapy. While effector-memory CD8+ T lymphocytes are essential for viremia control, few vaccines elicit such cellular immunity that could be potently recalled upon viral infection. Here, we investigated a program death-1 (PD1)-based vaccine by fusion of simian immunodeficiency virus capsid antigen to soluble PD1. Homologous vaccinations suppressed setpoint viremia to undetectable levels in vaccinated macaques following a high-dose intravenous challenge by the pathogenic SHIVSF162P3CN. Poly-functional effector-memory CD8+ T cells were not only induced after vaccination, but were also recalled upon viral challenge for viremia control as determined by CD8 depletion. Vaccine-induced effector memory CD8+ subsets displayed high cytotoxicity-related genes by single-cell analysis. Vaccinees with sustained viremia suppression for over two years responded to boost vaccination without viral rebound. These results demonstrated that PD1-based vaccine-induced effector-memory CD8+ T cells were recalled by AIDS virus infection, providing a potential immunotherapy for functional cure.

In vivo electroporation of a codon-optimized BERopt DNA vaccine protects mice from pathogenic Mycobacterium tuberculosis aerosol challenge.

DNA vaccines have been extensively studied as preventative and therapeutic interventions for various infectious diseases such as tuberculosis, HIV/AIDS and influenza. Despite promising progresses made, improving the immunogenicity of DNA vaccine remains a technical challenge for clinical development. In this study, we investigated a tuberculosis DNA vaccine BERopt, which contained a codon-optimized fusion immunogen Ag85B-ESAT-6-Rv2660c for enhanced mammalian cell expression and immunogenicity. BERopt immunization through in vivo electroporation in BALB/c mice induced surprisingly high frequencies of Ag85B tetramer+ CD8+ T cells in peripheral blood and IFN-γ-secreting CD8+ T cells in splenocytes. Meanwhile, the BERopt vaccine-induced long-lasting T cell immunity protected BALB/c mice from high dose viral challenge using a modified vaccinia virus Tiantan strain expressing mature Ag85B protein (MVTT-m85B) and the virulent M. tb H37Rv aerosol challenge. Since the BERopt DNA vaccine does not induce anti-vector immunity, the strong immunogenicity and protective efficacy of this novel DNA vaccine warrant its future development for M. tb prevention and immunotherapy to alleviate the global TB burden.

DNA prime/MVTT boost regimen with HIV-1 mosaic Gag enhances the potency of antigen-specific immune responses.

HIV-1 diversity and latent reservoir are the major challenges for the development of an effective AIDS vaccine. It is well indicated that Gag-specific CD8+ T cells serve as the dominant host immune surveillance for HIV-1 control, but it still remains a challenge for vaccine design to induce broader and stronger cytotoxic T cell immunity against the virus. Genetic variation of the HIV-1 gag gene across different clades is one of the reasons for the reduction of antigenic epitope coverage. Here, we report an immunization strategy with heterologous vaccines expressing a mosaic Gag antigen aimed to increase antigenic breadth against a wider spectrum of HIV-1 strains. Priming using a DNA vaccine via in vivo electroporation, followed by boosting with a live replication-competent modified vaccinia TianTan (MVTT) vectored vaccine, elicited greater and broader protective Gag-specific immune responses in mice. Compared to DNA or MVTT homologous immunization, the heterologous DNA/MVTT vaccination resulted in higher frequencies of broadly reactive, Gag-specific, polyfunctional, long-lived cytotoxic CD8+ T cells, as well as increased anti-Gag antibody titer. Importantly, the DNA/MVTT heterologous vaccination induced protection against EcoHIV and mesothelioma AB1-Gag challenges. In summary, the stronger protective Gag-specific immunity induced by the heterologous regimen using two safe vectors shows promise for further development to enhance anti-HIV-1 immunity. Our study has important implications for immunogen design and the development of an effective HIV-1 heterologous vaccination strategy.

Caveolin-1 deficiency protects pancreatic ß cells against palmitate-induced dysfunction and apoptosis.

Lipotoxicity leads to insulin secretion deficiency, which is among the important causes for the onset of type 2 diabetes mellitus. Thus, the restoration of ß-cell mass and preservation of its endocrine function are long-sought goals in diabetes research. Previous studies have suggested that the membrane protein caveolin-1 (Cav-1) is implicated in ß-cell apoptosis and insulin secretion, however, the underlying mechanisms still remains unclear. Our objective is to explore whether Cav-1 depletion protects pancreatic ß cells from lipotoxicity and what are the underlying mechanisms. In this study, we found that Cav-1 silencing significantly promoted ß-cell proliferation, inhibited palmitate (PA)-induced pancreatic ß-cell apoptosis and enhanced insulin production and secretion. These effects were associated with enhanced activities of Akt and ERK1/2, which in turn downregulated the expression of cell cycle inhibitors (FOXO1, GSK3ß, P21, P27 and P53) and upregulated the expression of Cyclin D2 and Cyclin D3. Subsequent inhibition of PI3K/Akt and ERK/MAPK pathways abolished Cav-1 depletion induced ß-cell mass protection. Furthermore, under PA induced endoplasmic reticulum (ER) stress, Cav-1 silencing significantly reduced eIF2α phosphorylation and the expression of ER stress-responsive markers BiP and CHOP, which are among the known sensitizers of lipotoxicity. Our findings suggest Cav-1 as potential target molecule in T2DM treatment via the preservation of lipotoxicity-induced ß-cell mass reduction and the attenuation of insulin secretion dysfunction.

Brief introduction of current technologies in isolation of broadly neutralizing HIV-1 antibodies.

HIV/AIDS has become a worldwide pandemic. Before an effective HIV-1 vaccine eliciting broadly neutralizing monoclonal antibodies (bnmAbs) is fully developed, passive immunization for prevention and treatment of HIV-1 infection may alleviate the burden caused by the pandemic. Among HIV-1 infected individuals, about 20% of them generated cross-reactive neutralizing antibodies two to four years after infection, the details of which could provide knowledge for effective vaccine design. Recent progress in techniques for isolation of human broadly neutralizing antibodies has facilitated the study of passive immunization. The isolation and characterization of large panels of potent human broadly neutralizing antibodies has revealed new insights into the principles of antibody-mediated neutralization of HIV. In this paper, we review the current effective techniques in broadly neutralizing antibody isolation.

Mycobacterium tuberculosis infection and vaccine development.

Following HIV/AIDS, tuberculosis (TB) continues to be the second most deadly infectious disease in humans. The global TB prevalence has become worse in recent years due to the emergence of multi-drug resistant (MDR) and extensively-drug resistant (XDR) strains, as well as co-infection with HIV. Although Bacillus Calmette-Guérin (BCG) vaccine has nearly been used for a century in many countries, it does not protect adult pulmonary tuberculosis and even causes disseminated BCG disease in HIV-positive population. It is impossible to use BCG to eliminate the Mycobacterium tuberculosis (M. tb) infection or to prevent TB onset and reactivation. Consequently, novel vaccines are urgently needed for TB prevention and immunotherapy. In this review, we discuss the TB prevalence, interaction between M. tb and host immune system, as well as recent progress of TB vaccine research and development.

Antigen spreading-induced CD8+T cells confer protection against the lethal challenge of wild-type malignant mesothelioma by eliminating myeloid-derived suppressor cells.

A key focus in cancer immunotherapy is to investigate the mechanism of efficacious vaccine responses. Using HIV-1 GAG-p24 in a model PD1-based DNA vaccine, we recently reported that vaccine-elicited CD8+ T cells conferred complete prevention and therapeutic cure of AB1-GAG malignant mesothelioma in immunocompetent BALB/c mice. Here, we further investigated the efficacy and correlation of protection on the model vaccine-mediated antigen spreading against wild-type AB1 (WT-AB1) mesothelioma. We found that this vaccine was able to protect mice completely from three consecutive lethal challenges of AB1-GAG mesothelioma. Through antigen spreading these animals also developed tumor-specific cytotoxic CD8+ T cells, but neither CD4+ T cells nor antibodies, rejecting WT-AB1 mesothelioma. A majority of these protected mice (90%) were also completely protected against the lethal WT-AB1 challenge. Adoptive cell transfer experiments further demonstrated that antigen spreading-induced CD8+ T cells conferred efficacious therapeutic effects against established WT-AB1 mesothelioma and prevented the increase of exhausted PD-1+ and Tim-3+ CD8+ T cells. A significant inverse correlation was found between the frequency of functional PD1-Tim3- CD8+ T cells and that of MDSCs or tumor mass in vivo. Mechanistically, we found that WT-AB1 mesothelioma induced predominantly polymorphonuclear (PMN) MDSCs in vivo. In co-cultures with efficacious CD8+ T cells, a significant number of PMN-MDSCs underwent apoptosis in a dose-dependent way. Our findings indicate that efficacious CD8+ T cells capable of eliminating both tumor cells and MDSCs are likely necessary for fighting wild-type malignant mesothelioma.

Simian immunodeficiency virus infection evades vaccine-elicited antibody responses to V2 region.

OBJECTIVES: An effective AIDS vaccine should elicit protective antibody responses against HIV/simian immunodeficiency virus (SIV) infection. We recently reported that mucosal priming with a replicating modified vaccinia Tiantan virus (MVTTgpe)-based vaccine regimen induces durable protection against pathogenic SIVmac239 infection in rhesus monkeys. Here, we aim to conduct a comprehensive analysis on antigenic determinants recognized by specific antibody responses generated by vaccination and SIVmac239 infection. METHODS: A novel yeast surface displayed antigen library of entire SIVmac239 envelope (Env) glycoprotein was established and validated to map the major antigenic determinants (MAD) in monkey sera elicited by vaccination and infection. MAD-directed antibody responses were further analyzed for correlation of protection. RESULTS AND CONCLUSIONS: The yeast surface displayed library allows the mapping of SIV-specific linear and conformational MAD. The MVTTgpe-based regimen induces antibodies targeting mainly to 6 antigenic domains covering the entire gp160. Critically, this regimen induced a uniquely predominant antibody response against a distinct MAD in variable region 2 (V2) as compared with the Ad5gpe-based vaccine and SIVmac239 infection. This MAD was associated with a higher titer of anti-V2 antibody responses, which was inversely correlated with peak and set-point viral loads. Unexpectedly, the pathogenic SIVmac239 challenge evaded the vaccine-elicited anti-V2 antibody response. Instead of recalling B-cell memory responses to the V2 MAD, viral infection directed anti-V1V2 antibodies primarily to V1 region. Moreover, the anti-V1V2 antibody responses diminished significantly in infected macaques after they enter the stage of simian AIDS. Our findings have critical implications to AIDS vaccine efforts with focus on V2 region.