Optimal decision-making in relieving global high temperature-related disease burden by data-driven simulation.

The rapid acceleration of global warming has led to an increased burden of high temperature-related diseases (HTDs), highlighting the need for advanced evidence-based management strategies. We have developed a conceptual framework aimed at alleviating the global burden of HTDs, grounded in the One Health concept. This framework refines the impact pathway and establishes systematic data-driven models to inform the adoption of evidence-based decision-making, tailored to distinct contexts. We collected extensive national-level data from authoritative public databases for the years 2010-2019. The burdens of five categories of disease causes - cardiovascular diseases, infectious respiratory diseases, injuries, metabolic diseases, and non-infectious respiratory diseases - were designated as intermediate outcome variables. The cumulative burden of these five categories, referred to as the total HTD burden, was the final outcome variable. We evaluated the predictive performance of eight models and subsequently introduced twelve intervention measures, allowing us to explore optimal decision-making strategies and assess their corresponding contributions. Our model selection results demonstrated the superior performance of the Graph Neural Network (GNN) model across various metrics. Utilizing simulations driven by the GNN model, we identified a set of optimal intervention strategies for reducing disease burden, specifically tailored to the seven major regions: East Asia and Pacific, Europe and Central Asia, Latin America and the Caribbean, Middle East and North Africa, North America, South Asia, and Sub-Saharan Africa. Sectoral mitigation and adaptation measures, acting upon our categories of Infrastructure & Community, Ecosystem Resilience, and Health System Capacity, exhibited particularly strong performance for various regions and diseases. Seven out of twelve interventions were included in the optimal intervention package for each region, including raising low-carbon energy use, increasing energy intensity, improving livestock feed, expanding basic health care delivery coverage, enhancing health financing, addressing air pollution, and improving road infrastructure. The outcome of this study is a global decision-making tool, offering a systematic methodology for policymakers to develop targeted intervention strategies to address the increasingly severe challenge of HTDs in the context of global warming.

Theoretical evaluation of the effect of bimetallic Au-based alloy catalysts on initial N2 electroreduction pathways.

Theoretical studies on the effect of bimetallic Au-based alloy catalysts on initial N2 electroreduction pathways at the present simulated electrode/aqueous interfaces based on DFT calculations are conducted in this work. The calculated results indicate that the alloying of Au with the transition metals Ni, Pd, Pt, Ru and Ta can facilitate the activation of N2 molecules in the presence of the electrode/aqueous interface, which may be derived from the kinetic overpotential of the outer Helmholtz plane. The N2 reduction pathway may be adsorption strength-dependent on N2, in which the incorporation of transition metals with a strong chemical affinity for N2 molecules may lead to a dissociative mechanism via the initial NN bond cleavage pathway, whereas the incorporation of transition metals with medium N2 binding strength may make N2 reduction proceed by the associative mechanism via the initial N2H formation pathway. The barriers of the initial N2 electroreduction into N2H species can be notably decreased after alloying Au with Ni, Pd, Pt, Ru and Ta compared with that on the Au electrode and the lowest N2H formation barriers can be obtained in these bimetallic Au-based alloy surfaces with an atomic ratio of 1 : 1, suggesting the strongest electrocatalytic activity. Further changing the atomic ratio leads to a notably increased formation barrier of N2H species, which can be explained by the Sabatier principle. It is concluded that the incorporation of Ni, Pd, Pt and Ru into Au can remarkably enhance the electrocatalytic activity since the HER barriers are notably higher than those of N2H formation, whereas the alloying of Au with Ta may not be able to effectively improve the N2 reduction performance due to the uninhibited HER. The present theoretical evaluations provide a promising method to design efficient bimetallic alloy electrocatalysts for N2 electroreduction into NH3 products.

Developmental validation of forensic DNA-STR kits: Expressmarker 16+10Y and expressmarker 16+18Y.

DNA-STR analysis is widely used in the forensic science field and obtaining results in shorter time is highly demanded. The developed forensic STR Kit, referred to as Expressmarker 16+10Y (EX16+10Y) and Expressmarker 16+18Y (EX16+18Y), could amplify the common autosomal and Y chromosome STR loci simultaneously. The kits are validated by a series of tests, including DNA mixtures, stutter ratios, PCR based studies, species specificities, inhibitors, sensitivity, sizing precision, reproducibility and parallel tests. The results demonstrated that EX16+10Y and EX16+18Y were useful tools for rapid criminal investigation.

[Development of a Forensic Multiplex Amplification STR Kit for 15 Autosomal STR Loci and 10 Y-STR Loci].

OBJECTIVE: To establish a multiplex STR genotyping method for autosomal STR and Y-STR loci in forensic biological practice. METHODS: Widely used autosomal STR loci and Y-STR loci were selected. A set of PCR primers was designed, and a 5-dye fluorescent labeled STR multiplex PCR reagent kit was developed. RESULTS: A kit was developed which can simultaneously detect 15 autosomal STR loci, 10 Y-STR loci, and an Amelogenin. CONCLUSION: The 15 autosomal STR plus 10 Y-STR kit in combination with capillary electrophoresis method was used to STR genotyping with accurate and reliable results. The new one-step testing kit can potentially be widely used in forensic cases and DNA databank in the future.

Developmental validation of the EX20+4 system.

The EX20+4Y System is a polymerase chain reaction (PCR)-based amplification kit that enables typing of 19 autosomal short tandem repeat (STR) loci (i.e., CSF1PO, D13S317, D16S539, D18S51, D21S11, D3S1358, D5S818, D7S820, D8S1179, FGA, TH01, TPOX, vWA, Penta D, Penta E, D2S1338, D19S433, D12S391, D6S1043), four widely used Y chromosome-specific STR (Y-STR) loci (DYS458, DYS456, DYS391, DYS635), and amelogenin. In this study, this multiplex system was validated for sensitivity of detection, DNA mixtures, inhibitor tolerance, species specificity based on the Scientific Working Group on DNA Analysis methods (SWGDAM) developmental validation guidelines, and the Chinese criteria for the human fluorescent STR multiplex PCR reagent. The results show that the EX20+4 System is a robust and reliable amplification kit which can be used for human identification testing.

Developmental validation of a forensic rapid DNA-STR kit: Expressmarker 16.

DNA-STR analysis is widely used in the forensic science field and has important requirements on the analysis time to obtain faster inspections. The developed forensic STR kit, referred to as Expressmarker 16 (EX16), could shorten the amplification time to a minimum of 35min. It enables 16 STR loci to be co-detected, including 13 CODIS loci, D2S1338, D6S1043 and Amelogenin loci. The kit is validated by a series of tests formed by DNA mixtures, stutter ratios, optimized PCR protocols based on annealing temperature research, species specificities, inhibitors, sensitivity, and parallel tests according to FBI QAS (2009/2011) (QAS, 2009; SWGDAM, 2010). The results demonstrated that EX16 was a useful tool for rapid criminal investigation.

A guide RNA sequence design platform for the CRISPR/Cas9 system for model organism genomes.

Cas9/CRISPR has been reported to efficiently induce targeted gene disruption and homologous recombination in both prokaryotic and eukaryotic cells. Thus, we developed a Guide RNA Sequence Design Platform for the Cas9/CRISPR silencing system for model organisms. The platform is easy to use for gRNA design with input query sequences. It finds potential targets by PAM and ranks them according to factors including uniqueness, SNP, RNA secondary structure, and AT content. The platform allows users to upload and share their experimental results. In addition, most guide RNA sequences from published papers have been put into our database.

[Forensic application of expressmarker 22 STR loci direct PCR amplification kit].

OBJECTIVE: To explore the application value of Expressmarker 22 STR loci direct PCR amplification kit. METHODS: One thousand nine hundred and forty-eight samples (including samples spotted on FTA cards, filter papers and case samples) were tested using Expressmarker 22 STR loci direct PCR amplification kit. At the same time, all were tested using Sinofiler kit, Identifiler kit and PowerPlex 16 kit respectively for comparison. The genotypes were compared at the same STR loci among these four kits to test the sensitivity and accuracy of Expressmarker 22 STR loci direct PCR amplification kit. RESULTS: 97.79% samples were successfully typed using Expressmarker 22 STR loci direct PCR amplification kit. The genotype profiles of the same samples using Expressmarker 22 STR loci direct PCR amplification kit were consistent with Sinofiler kit, Identifiler kit and PowerPlex 16 kit at the same STR loci. CONCLUSION: Expressmarker 22 STR loci direct PCR amplification kit can provide huge information and accurate results

[Rapid DNA identification using 6+1 STR kit and EX-Q20 electrophoresis].

OBJECTIVE: To establish a rapid STR genotyping method for individual identification. METHODS: Two hundred blood samples from FTA were collected. Equal amount of blood were collected by puncher and analyzed using two methods (6+1 STR kit in combination with EX-Q20 electrophoresis and Sinofiler kit in combination with POP4 electrophoresis). Consuming time and results of two methods were compared. RESULTS: 6+1 STR kit in combination with EX-Q20 electrophoresis method can obtain all genotyping results and be shorter time. CONCLUSION: 6+1 STR kit in combination with EX-Q20 electrophoresis method is used to STR genotyping with accurate, reliable results and this new method is potential value in mass personnel investigation and comparison in major criminal cases. It also can raise the work efficiency.

[Treatment of 58 cases of vitiligo by electro-plum-blossom needle therapy combined with catgut implantation at acupoints under TDP radiation].

OBJECTIVE: To search for a method for increasing therapeutic effect on vitiligo. METHODS: One hundred and sixteen cases were randomly divided into a treatment group and a control group, 58 cases in each group. The treatment group were treated with electro-plum-blossom needle therapy plus catgut implantation at local acupoints under TDP radiation, and the control group with external application of sicorten. Their short-term and long-term therapeutic effects were observed. RESULTS: The short-term total effective rate was 98.3% in the treatment group and 74.1% in the control group with a significant difference between the two groups (P < 0.05). CONCLUSION: Electro-plum-blossom needle therapy plus catgut implantation at acupoints has a better therapeutic effect on vitiligo with no adverse effect.

[Combinative effects of FAP-1 antisense oligonucleotide and carboplatin on apoptosis of ovarian cancer cell SKOV3].

BACKGROUND & OBJECTIVE: Recent studies have shown that overexpression of Fas associated phosphatase-1 (FAP-1) can been detected in human ovarian cancer cell line SKOV3, suggesting that this overexpression may play an important role in the tumorigenesis and drug resistance of ovarian cancer. This study was designed to explore the effects of fas associated phosphatase-1 antisense oligonucleotide (FAP-1 ASODN) combined with carboplatin on the apoptosis of ovarian cancer cell SKOV3. METHODS: Antisense oligonucleotide technique was used to transfect FAP-1 ASODN into SKOV3 cells. The expression levels of FAP-1 mRNA of SKOV3 cells with or without FAP-1 ASODN transfection were determined by reverse transcription- polymerase chain reaction (RT-PCR). The cell cycle and apoptotic rate were analyzed by flow cytometry (FCM). The growth and proliferation of SKOV3 cells were observed by MTT assay. RESULTS: After transfected FAP-1 ASODN for 24 hours, the expression of FAP-1 mRNA in SKOV3 cells was obviously reduced compared with those of the control and FAP-1 SODN transfection groups. When induced apoptosis with 40 microg/ml carboplatin for 24-72 hours, FCM results showed the apoptotic rate of "carboplatin+FAP-1 ASODN" group was higher than those of "carboplatin" group and "ASODN" group (P< 0.05), and the cell cycle was blocked in G1 phase. MTT results showed the cell inhibitory rate of "carboplatin+FAP-1 ASODN" group was 1.5-2 times those of "carboplatin" group and "ASODN" group (P< 0.05); but no significant difference was found between "carboplatin" group and "carboplatin+FAP-1 SODN" group (P >0.05). CONCLUSION: FAP-1 ASODN transfection can suppress the expression of FAP-1 gene in SKOV3 cells and enhance the cell sensitivity to apoptosis induced by carboplatin, which implies that FAP-1 ASODN may reverse the drug resistance in ovarian cancer.

[The manufacture of pelvic mirror physical model using rapid prototyping].

OBJECTIVE: To study the manufacture of pelvic mirror physical model using rapid prototyping and the accuracy of the models. METHODS: The pelvic CT images were acquired by spiral CT thin slice scanning, and the slicing data of pelvis were created from these CT images by computer image-processing. Then the pelvic mirror physical model was manufactured using rapid prototyping. The model of a cadaver pelvis and the pelvic model of an experimental dog were manufactured respectively using the method above, and the accuracy of the models were examined. RESULTS: The model of the cadaver pelvis manufactured with this method was very similar to the cadaver pelvis. So was the pelvic model of the experimental dog. CONCLUSION: The manufacture of pelvic mirror physical model using rapid prototyping was feasible, and the models were quite accurate.

[Gene cloning and prokaryotic expression of the PID domain of human DOC-2 molecule].

AIM: To clone the PID domain of human DOC-2 (nDOC-2) and express it in E.coli DH5alpha. METHODS: The cDNA fragment encoding the PID domain of nDOC-2 was amplified by RT-PCR from normal human ovarian tissue and cloned to pUC19. The DNA fragment from the pUC19-nDOC-2 digested with BamH I and EcoR I was ligated to the BamH I/EcoR I digested prokaryotic expression vector pGEX-4T-1.The expression of fusion protein was induced with IPTG and the expressed product was identified by SDS-PAGE. RESULTS: (1)The sequencing and endonucleases digestion analysis showed that the fragment of nDOC-2 gene was insert into vectors pUC19 and pGEX-4T-1;(2)SDS-PAGE showed the nDOC-2 gene had been expressed in E.coli DH5alpha. CONCLUSION: The PID domain of nDOC-2 was expressed successfully in prokaryote, which makes preparation for further researching the function of DOC-2 and preparing antibodies to DOC-2 protein.