Effectiveness of the secondary distribution of HIV self-testing with and without monetary incentives among men who have sex with men living with HIV in China: study protocol for a randomized controlled trial

BACKGROUND: The HIV epidemic is still expanding among men who have sex with men (MSM) in China, but HIV testing rates remain suboptimal. Network-based interventions, such as secondary distribution, have shown promise to expand HIV self-testing (HIVST) among partners of MSM living with HIV (MLWH) but have not been widely implemented. Monetary incentives could enhance the secondary distribution of HIVST in some settings. We will conduct a randomized controlled trial to examine the effectiveness of monetary incentives in expanding the secondary distribution of HIVST among MLWH in China. METHODS: We will recruit 200 eligible participants at three antiretroviral therapy (ART) clinics in China. Participants are eligible if they are 18 years of age or over, assigned as male at birth, have had anal sex with men, are living with HIV, are willing to apply for the HIVST kit at ART clinics, and are willing to provide personal contact information for follow-up. Eligible participants will be randomly assigned in a 1:1 ratio to one of two groups: standard secondary distribution group and secondary distribution group with monetary incentives. Participants (defined as "index") will distribute the HIVST kits to members of their social network (defined as "alter") and will be required to complete a baseline survey and a 3-month follow-up survey. All alters will be encouraged to report their testing results by taking photos of used kits and completing an online survey. The primary study outcomes will compare the mean number of alters and newly-tested alters motivated by each index participant in each group. Secondary study outcomes will include the mean number of alters who tested positive, the cost per person tested, and the cost per HIV diagnosed for each group. DISCUSSION: Few studies have evaluated interventions to enhance the implementation of secondary distribution. Our study will provide information on the effectiveness of monetary incentives in expanding HIVST secondary distribution among MLWH. The findings of this trial will contribute to implementing HIVST secondary distribution services among MLWH in China and facilitating HIV case identifications. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200064517; http://www.chictr.org.cn/showproj.aspx?proj=177896 . Registered on 10th October 2022

Loss‐of‐Function Genetic Screening Identifies Aldolase A as an Essential Driver for Liver Cancer Cell Growth Under Hypoxia

Background and aims: Hypoxia is a common feature of the tumor microenvironment (TME), which promotes tumor progression, metastasis, and therapeutic drug resistance through a myriad of cell activities in tumor and stroma cells. While targeting hypoxic TME is emerging as a promising strategy for treating solid tumors, preclinical development of this approach is lacking in the study of HCC. Approach and results: From a genome-wide CRISPR/CRISPR-associated 9 gene knockout screening, we identified aldolase A (ALDOA), a key enzyme in glycolysis and gluconeogenesis, as an essential driver for HCC cell growth under hypoxia. Knockdown of ALDOA in HCC cells leads to lactate depletion and consequently inhibits tumor growth. Supplementation with lactate partly rescues the inhibitory effects mediated by ALDOA knockdown. Upon hypoxia, ALDOA is induced by hypoxia-inducible factor-1α and fat mass and obesity-associated protein-mediated N6 -methyladenosine modification through transcriptional and posttranscriptional regulation, respectively. Analysis of The Cancer Genome Atlas shows that elevated levels of ALDOA are significantly correlated with poor prognosis of patients with HCC. In a screen of Food and Drug Administration-approved drugs based on structured hierarchical virtual platforms, we identified the sulfamonomethoxine derivative compound 5 (cpd-5) as a potential inhibitor to target ALDOA, evidenced by the antitumor activity of cpd-5 in preclinical patient-derived xenograft models of HCC. Conclusions: Our work identifies ALDOA as an essential driver for HCC cell growth under hypoxia, and we demonstrate that inhibition of ALDOA in the hypoxic TME is a promising therapeutic strategy for treating HCC

RNA-binding protein RALY reprogrammes mitochondrial metabolism via mediating miRNA processing in colorectal cancer

Objective: Dysregulated cellular metabolism is a distinct hallmark of human colorectal cancer (CRC). However, metabolic programme rewiring during tumour progression has yet to be fully understood. Design: We analysed altered gene signatures during colorectal tumour progression, and used a complex of molecular and metabolic assays to study the regulation of metabolism in CRC cell lines, human patient-derived xenograft mouse models and tumour organoid models. Results: We identified a novel RNA-binding protein, RALY (also known as hnRNPCL2), that is highly associated with colorectal tumour aggressiveness. RALY acts as a key regulatory component in the Drosha complex, and promotes the post-transcriptional processing of a specific subset of miRNAs (miR-483, miR-676 and miR-877). These miRNAs systematically downregulate the expression of the metabolism-associated genes (ATP5I, ATP5G1, ATP5G3 and CYC1) and thereby reprogramme mitochondrial metabolism in the cancer cell. Analysis of The Cancer Genome Atlas (TCGA) reveals that increased levels of RALY are associated with poor prognosis in the patients with CRC expressing low levels of mitochondrion-associated genes. Mechanistically, induced processing of these miRNAs is facilitated by their N6-methyladenosine switch under reactive oxygen species (ROS) stress. Inhibition of the m6A methylation abolishes the RALY recognition of the terminal loop of the pri-miRNAs. Knockdown of RALY inhibits colorectal tumour growth and progression in vivo and in organoid models. Conclusions: Collectively, our results reveal a critical metabolism-centric role of RALY in tumour progression, which may lead to cancer therapeutics targeting RALY for treating CRC

Uncertainties of carbon emission from hydroelectric reservoirs

Anthropogenic greenhouse gas (GHG) emissions have substantially contributed to intensification of heavy precipitation and thus the risk of flood occurrence, and this anthropogenic climate change is now likely to continue for many centuries. Thus, precise quantification of human-induced GHG emissions is urgently required for modeling future global warming and precipitation changes, which is strongly linked to flood disasters. Recently, GHG evasion from hydroelectric reservoirs was estimated to be 48 Tg C as CO2 and 3 Tg C as CH4 annually, lower than earlier estimate (published in Nature Geoscience; 2011). Here, we analyzed the uncertainties of GHG emissions from hydroelectric reservoirs, that is, reservoir surface area, data paucity and carbon emission relating to ecological zone, and argued that GHG evasion from global hydroelectric reservoirs has been largely under-estimated. Our study hopes to improve the quantification for future researches

A functional Variant (Rs35592567) in TP63 at 3q28 is Associated with Gastric Cancer Risk via Modifying its Regulation by MicroRNA-140

Background/Aims: TP63 was believed to play an important role in the development of many malignancies, while the polymorphisms located at the miRNA binding sites within the 3’UTR of TP63 mRNA may interfere with its expression. In this study, we aimed to study the role of TP63 regulation in the tumorigenesis of gastric cancer (GC). Methods: Computational and luciferase analysis were used to search and confirm the target of miR-140. Real-time PCR, western-blot, MTT assay, and flow cytometry cell cycle analysis were utilized to explore the molecular pathway of miR-140 involved in the progression of GC. Results: TP63 was identified as a direct target gene of miR-140. In HT-29 cells over-expressing miR-140, the luciferase activity was decreased when the cells were transfected with wild-type TP63 3’UTR, but remained unchanged when the cells were transfected with mutant 1 and mutant 2 TP63 3’UTR. In addition, the level of TP63 in HT-29 cells transfected with miR-140 mimic was evidently down-regulated, whereas the level of TP63 in HT-29 cells transfected with miR-140 inhibitor was significantly up-regulated. Furthermore, based on the results from MTT assay and flow cytometry cell cycle analysis, HT-29 cells transfected with miR-140 mimics were associated with significantly higher viability compared to the cells transfected with the control plasmid, suggesting that an increased expression of miR-140 protected HT-29 cells against apoptosis. Finally, when miR-140 expression was high, the number of cells at the G1 phase was notably increased, accompanied by a remarkably diminished number of cells at the S phase. Conclusions: The rs35592567 polymorphism in TP63 affected the expression of TP63 by interfering with its interaction with miR-140, and could serve as an explanation for the increased risk of GC

Evaluation of Photovoltaic Consumption Potential of Residential Temperature-Control Load Based on ANP-Fuzzy and Research on Optimal Incentive Strategy

Temperature-control loads, such as residential air conditioners (ACs) and electric water heaters (EWHs), have become important demand response resources in the power system. However, due to the impact of various factors on users’ response behavior, it has been difficult for power grid operators to accurately evaluate the response potential under complex factor relationships to derive optimal incentive strategy. Therefore, it cannot achieve a win-win economic benefit between the grid and users. In this paper, a method combining Analytic Network Process (ANP) and Fuzzy logical inference is proposed to predict the user’s willingness firstly by taking residential AC load as an example. The weight of each factor affecting users’ willingness is analyzed, and main factors are selected as inputs of fuzzy logic inference to derive the willingness of the resident to actively regulate the AC. Then, this method is applied in evaluating the response potential of certain residential area in Beijing according to the survey. By further considering users’ house size and the sacrificed comfort temperature under the incentive strategy, the power potential curve of the AC load under different incentives is obtained by using the first-order equivalent thermal parameter (ETP) model and the regulation willingness. Finally, with the objective of maximizing the consumption of the photovoltaic (PV) power, the optimal operation is achieved through the coordinated regulation of residential ACs and EWHs based on the potential curve, and the corresponding optimal incentive strategy for the flexible temperature-control loads is obtained. Simulation results show that the optimal incentive strategy proposed not only increases the PV consumption ratio to 98.35% with an increase of 24.71%, but also maximizes the economic benefits of both sides of the power grid and users. This method of deriving incentive strategy can be used as a reference for grid companies to formulate the incentive strategy to realize optimal operation, such as the maximum new energy consumption

CO2 partial pressure and CO2 emission in the Lower Mekong River

CO2 evasion from freshwaters is recently included in assessing global carbon budgets, while large uncertainty of global estimates results from incomplete spatial coverage of aquatic carbon emission. Here we examined the dissolved inorganic carbon (DIC) and carbon dioxide partial pressure (pCO2) in riverine water from historical records at 46 stations for the period 1972–1998 in the Lower Mekong River (LMR). The river system presented an exceptional temporal and spatial variability of dissolved inorganic carbon (DIC) species. The alkalinity concentration of the LMR varied from 687 to 3189 μeq/l with an average of 1524 μeq/l (median value: 1586 μeq/l), 1.2 times the global median value. Spatial patterns showed diminishing alkalinity downstream at the main-channel stations along the LMR. Similar to many other Himalayan rivers, alkalinity varied seasonally and inversely related to river runoff with a variation factor of 1.2–1.6, despite a water dilution of 7-fold to 13-fold in the summer flood season. The pCO2 levels ranged from 224 to 5970 μatm with a total average of 1090 μatm and obvious monthly and spatial variations. Under-saturated pCO2 samples (\u3c390 \u3eμatm) primarily occurred in the high-flow period. pCO2 at the main-channel stations increased downstream and averaged from 720 μatm (Mukdahan) to 1670 μatm (Can Tho). Calculated water-to-air CO2 degassing from the Mekong River was 71 mol/m2/yr, thus 6.8 Tg C/yr as CO2 was released to the atmosphere, 1.5-fold the sea-ward DIC export (4.5 Tg C/yr). Basin characteristics influences on pCO2 from 25 global rivers demonstrated that non-carbonate rocks significantly contributed to pCO2, population density, agricultural practices, elevation and slope decreased pCO2, while forest significantly increased pCO2. Our results demonstrated the essential need to consider river water area as an essential atmospheric CO2 source, albeit this atmospheric flux, representing significant riverine carbon budgets, was highly variable at temporal and spatial scales

Chemical weathering and CO2 consumption in the Lower Mekong River

Data on river water quality from 42 monitoring stations in the Lower Mekong Basin obtained during the period 1972–1996 was used to relate solute fluxes with controlling factors such as chemical weathering processes. The total dissolved solid (TDS) concentration of the Lower Mekong varied from 53 mg/L to 198 mg/L, and the median (114 mg/L) was compared to the world spatial median value (127 mg/L). Total cationic exchange capacity (Tz+) ranged from 729 to 2607 μmolc/L, and the mean (1572 μmolc/L) was 1.4 times higher than the world discharge-weighted average. Calcium and bicarbonate dominated the annual ionic composition, accounting for ~ 70% of the solute load that equalled 41.2 × 109 kg/y. TDS and major elements varied seasonally and in a predictable way with river runoff. The chemical weathering rate of 37.7 t/(km2 y), with respective carbonate and silicate weathering rates of 27.5 t/(km2 y) (13.8 mm/ky) and 10.2 t/(km2 y) (3.8 mm/ky), was 1.5 times higher than the global average. The CO2consumption rate was estimated at 191 × 103 mol CO2/(km2 y) for silicate weathering, and 286 × 103 mol CO2/(km2 y) by carbonate weathering. In total, the Mekong basin consumed 228 × 109 mol CO2/y and 152 × 109 mol CO2/y by the combined weathering of carbonate and silicate, constituting 1.85% of the global CO2 consumption by carbonate weathering and 1.75% by silicates. This is marginally higher than its contribution to global water discharge ~ 1.3% and much higher than (more than three-fold) its contribution to world land surface area. Remarkable CO2 consumed by chemical weathering (380 × 109 mol/y) was similar in magnitude to dissolved inorganic carbon as HCO3−(370 × 109 mol/y) exported by the Mekong to the South China Sea. In this landscape, atmospheric CO2 consumption by rock chemical weathering represents an important carbon sink with runoff and physical erosion controlling chemical erosion