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PURPOSE OF REVIEW: Adherence-concentration-efficacy benchmarks have not been fully characterized for cisgender women using emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) oral daily pre-exposure prophylaxis (PrEP) for HIV prevention. RECENT FINDINGS: We conducted a systematic review to investigate current evidence on the adherence-concentration-efficacy relationship of tenofovir-diphosphate (TFV-DP) derived from FTC/TDF PrEP in dried blood spots (DBS) and peripheral mononuclear cells (PBMC) in cisgender women without HIV, including during pregnancy. We searched for completed and ongoing studies published before May 2024 in PubMed, Embase, Cochrane Library, CINAHL, and clinicaltrial.gov. Overall, 11 studies assessing adherence benchmarks focusing on (n = 5) or involving (n = 6) cisgender women were included. Women-specific median steady-state TFV-DP concentration for daily dosing ranged from 17 to 51 fmol/106 in PBMC and 1389 to 1685 fmol/punch in DBS in non-pregnant women; 50 to 71 fmol/106 in PBMC and 583 to 965 fmol/punch in DBS in pregnant women; and 618 to 1406 fmol/punch in DBS in postpartum women. DBS TFV-DP levels were 14-43% lower in pregnancy versus postpartum or non-pregnant periods, but PBMC TFV-DP levels appear to be comparable. Clinical and modeling studies demonstrate effective HIV protection for women taking at least four doses/week of oral TDF-based PrEP, and emerging evidence suggests that systemic drug levels are more likely to be predictive of efficacy than local tissue levels at the site of exposure. The preponderance of emerging evidence points to comparable efficacy and similar adherence requirement for women as men among those with detectable drug levels, although there was an indication that the highest achievable efficacy may be reached at a lower adherence level in men than women. In this review, we found evidence that women-specific TFV-DP adherence benchmarks in DBS and PBMC are within range of US-based historical thresholds derived from healthy men and women. Emerging evidence suggests that imperfect but adequate adherence to oral FTC/TDF PrEP with at least four doses/week provides sufficient HIV protection in cisgender women as it does in MSM, but more data are still needed to refine intrinsic achievable efficacy estimates for cisgender women.
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Background: Oral pre-exposure prophylaxis (PrEP) using co-formulated emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) is a potent HIV prevention method for men and women, with its efficacy highly dependent on adherence. A pivotal HIV efficacy study combined with a directly observed pharmacological study defined the thresholds for HIV protection in men who have sex with men (MSM), which are the keys to PrEP promotion and development of new PrEP agents. For African women at risk for HIV and belonging to a priority group considered due to disproportionately high incident HIV infections, the variable adherence in PrEP clinical trials and the limited pharmacologic data have resulted in a lack of clarity about the PrEP adherence required for HIV protection. We propose a study to quantify the adherence-concentration-efficacy thresholds of TDF/FTC PrEP among African cisgender women to inform decisions about optimal PrEP dosing and adherence for HIV protection. Methods: We randomized 45 low-risk HIV-uninfected African women, aged 18-30 years old, to directly observe the TDF/FTC PrEP of two, four, or seven doses per week for 8 weeks. A complementary age-matched pregnant women cohort at high risk of HIV, who will receive seven doses per week, was recruited (N = 15) with the primary aim of establishing benchmark concentrations in dried blood spots and peripheral blood mononuclear cells. Plasma, whole blood (WB), urine, hair, vaginal fluid, and vaginal tissue (non-pregnant women only) were archived for future testing. Drug concentrations were measured using methods validated for each biological matrix. Pharmacokinetic models were fitted to drug concentrations to quantify concentration-adherence thresholds. To define the drug concentrations associated with HIV protection, we applied the newly defined thresholds from the primary pharmacologic trial to the subset of women randomized to TDF/FTC or TDF in the Partners PrEP Study with the drug concentration assessed in plasma and WB samples. Multiple imputation was used to construct a data set with drug concentrations at each visit when an HIV test was performed for the entire cohort, replicating the work for MSM. Discussion: The proposed study generated the first African women-specific TDF-PrEP adherence-concentration-efficacy thresholds essential for guiding the accurate interpretation of TDF/FTC PrEP programs and clinical trials of novel HIV prevention products using TDF/FTC as an active control. Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT05057858).
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Locally advanced breast cancer (LABC) is a heterogeneous group of breast cancer that accounts for 10-30% of breast cancer cases. Despite the ongoing development of current treatment methods, LABC remains a severe and complex public health concern around the world, thus prompting the urgent requirement for innovative diagnosis and treatment strategies. The primary treatment challenges are inoperable clinical status and ineffective local control methods. With the rapid advancement of nanotechnology, inorganic nanoparticles (INPs) exhibit a potential application prospect in diagnosing and treating breast cancer. Due to the unique inherent characteristics of INPs, different functions can be performed via appropriate modifications and constructions, thus making them suitable for different imaging technology strategies and treatment schemes. INPs can improve the efficacy of conventional local radiotherapy treatment. In the face of inoperable LABC, INPs have proposed new local therapeutic methods and fostered the evolution of novel strategies such as photothermal and photodynamic therapy, magnetothermal therapy, sonodynamic therapy, and multifunctional inorganic nanoplatform. This article reviews the advances of INPs in local accurate imaging and breast cancer treatment and offers insights to overcome the existing clinical difficulties in LABC management.
Subject(s)
Breast Neoplasms , Humans , Breast Neoplasms/therapy , Female , Nanostructures/therapeutic use , Nanostructures/chemistry , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Animals , Photochemotherapy/methods , Inorganic Chemicals/chemistryABSTRACT
We evaluated hair tenofovir (TFV) concentrations as an adherence metric for HIV pre-exposure prophylaxis (PrEP) during pregnancy and postpartum and compared hair levels with tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). Overall, 152 hair samples from 102 women and 36 hair-DBS paired samples from 29 women were collected from a subset of women in a cluster randomized trial. Having a partner known to be living with HIV was associated with higher hair TFV levels (p<0.001). Hair TFV concentrations were strongly correlated with DBS TFV-DP levels (r=0.76, p<0.001), indicating hair as promising cumulative adherence metric for perinatal PrEP assessment.
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BACKGROUND: Community-based oral pre-exposure prophylaxis (PrEP) provision has the potential to expand PrEP coverage. HIV self-testing can facilitate PrEP community-based delivery but might have lower sensitivity than facility-based HIV testing, potentially leading to inappropriate PrEP use among people with HIV and subsequent development of drug resistance. We aimed to evaluate the impact of HIV self-testing use for PrEP scale-up. METHODS: We parameterised an agent-based network model, EMOD-HIV, to simulate generic tenofovir disoproxil fumarate and emtricitabine PrEP scale-up in western Kenya using four testing scenarios: provider-administered nucleic acid testing, provider-administered rapid diagnostic tests detecting antibodies, blood-based HIV self-testing, or oral fluid HIV self-testing. Scenarios were compared with a no PrEP counterfactual. Individuals aged 18-49 years with one or more heterosexual partners who screened HIV-negative were eligible for PrEP. We assessed the cost and health impact of rapid PrEP scale-up with high coverage over 20 years, and the budget impact over 5 years, using various HIV testing modalities. FINDINGS: PrEP coverage of 29% was projected to avert approximately 54% of HIV infections and 17% of HIV-related deaths among adults aged 18-49 years over 20 years; health impacts were similar across HIV testing modalities used to deliver PrEP. The percentage of HIV infections with PrEP-associated nucleoside reverse transcriptase inhibitor (NRTI) drug resistance was 0·6% (95% uncertainty intervals 0·4-0·9) in the blood HIV self-testing scenario and 0·8% (0·6-1·0) in the oral HIV self-testing scenario, compared with 0·3% (0·2-0·3) in the antibody rapid diagnostic testing scenario and 0·2% (0·1-0·2) in the nucleic acid testing scenario. Accounting for background NRTI resistance, we found similarly low proportions of drug resistance across scenarios. The budget impact of implementing PrEP using HIV self-testing and provider-administered rapid diagnostic tests were similar, while nucleic acid testing was approximately 50% more costly. INTERPRETATION: Scaling up PrEP using HIV self-testing has similar health impacts, costs, and low risk of drug resistance as provider-administered rapid diagnostic tests. Policy makers should consider leveraging HIV self-testing to expand PrEP access among those at HIV risk. FUNDING: The Bill and Melinda Gates Foundation.
Subject(s)
Anti-HIV Agents , HIV Infections , Nucleic Acids , Pre-Exposure Prophylaxis , Adult , Humans , HIV Infections/diagnosis , HIV Infections/drug therapy , HIV Infections/epidemiology , Anti-HIV Agents/therapeutic use , Kenya/epidemiology , Self-Testing , Emtricitabine/therapeutic use , Reverse Transcriptase Inhibitors/therapeutic use , HIV Testing , Nucleic Acids/therapeutic useABSTRACT
The study characterized the aroma-active compounds produced by sesame hulls at three roasting temperatures and analyzed the similarities and differences in the aroma profile of sesame hulls with whole seeds and kernels after roasting. Roasting hulls produced mainly furans, aldehydes, and ketones volatiles. 140 Compounds were identified as aroma-active compounds, including 36 key aroma compounds (odor activity value, OAV ≥ 1). Among them, furanone (caramel-like, OAV = 80), 3-methylbutanal (fruity, OAV = 124), and 2-methoxy-4-vinylphenol (burnt, smoky, OAV = 160) gave hulls (180 °C) sweet, burnt, and smoky aroma. Due to the contribution of vanillin (fatty, sweet milk, OAV = 45), 2-hydroxy-3-butanone (caramel-like, roast, OAV = 46), and 2-methoxy-4-vinylphenol (OAV = 78), hulls (200 °C) shown strong sweet and roast note. These results identified compounds that contributed significantly to the aroma of sesame hulls and elucidated the contribution of sesame hulls to the flavor of roasted whole seeds and sesame oil.
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BACKGROUND: The manubrium and body of the sternum are connected by the manubrium-sternum joint (MSJ). In performing the Nuss procedure for pectus excavatum patients, the body of the sternum is elevated as the operator flips correction bars upside down. Theoretically, the presence of the MSJ should allow elevation of the sternum body. However, does the MSJ secure sufficient elevation of the sternum? This study aims to elucidate this clinical question. METHODS: Seventy-four adult pectus excavatum patients with moderate to serious deformity (with Haller Index being equal to or greater than 5) were included in the study. The MSJ was open in all patients. For 29 patients, the sternum was elevated by only bar flipping (Non-Separation Group); for 45 patients, the sternum was horizontally separated after bar flipping (Separation Group). Whether or not additional elevation for Separation Group patients results from the division was observed, and the degree of the additional elevation was evaluated. Furthermore, 74 patients subjectively evaluated postoperative pain and gave scores with a Visual Analog Scale ranging from 0 (no pain) to 10 (intolerable pain). The VAS scores were compared between the two groups. RESULTS: In the Separation Group, the sternums of all patients achieved additional elevation from sternum separation. The pain scores were lower for the Separation Group than for the Non-Separation Group. CONCLUSION: Even when the MSJ is present, horizontal separation enhances the elevation of the sternum. Furthermore, horizontal separation of the sternum reduces postoperative pain.
Subject(s)
Funnel Chest , Manubrium , Sternum , Humans , Funnel Chest/surgery , Sternum/surgery , Male , Female , Manubrium/surgery , Adult , Young Adult , Treatment Outcome , Adolescent , Pain, Postoperative/etiology , Orthopedic Procedures/methods , Orthopedic Procedures/adverse effects , Pain MeasurementABSTRACT
Background: Severing part of the thorax prior to bar placement is effective to improve outcomes in performing the Nuss procedure for asymmetric pectus excavatum. This study aims to elucidate the patterns of severing to provide an ideal outcome. Methods: Three-dimensional biomechanical computer models were produced simulating the thoraxes of 10 actual patients with asymmetric pectus excavatum. Virtual surgical operation was performed on the 10 models in 4 patterns: group 1-no part of the thorax was severed (default group). Group 2-The sternum was severed (sternum-severing group). Group 3-The ribs on the affected side were severed (rib-severing group). Group 4-Both the sternum and ribs on the affected side were severed (sternum/rib-severing group). After performing this preparation, simulation of bar placement was performed. Comparing the pre- and postoperative shapes of the models, we examined whether symmetry improved for each group. Results: Symmetry of the chest wall improved for rib-severing group and sternum/rib-severing group. Asymmetry remained for default group and sternum-severing group. Conclusions: Performance of the Nuss procedure for asymmetric pectus excavatum does not greatly improve symmetry of the chest wall. Severing the ribs as an additional maneuver is effective to improve symmetry.
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The shrub encroachment caused by Caragana species (mainly C. microphylla, C. korshinskii, C. tibetica, C. stenophylla, and C. pygmaea) in the north temperate zone has significant impacts on ecosystems. Understanding the distribution of Caragana species' responses to climate change is increasingly relevant to the dynamic of shrub encroachment. In this study, we gathered 1124 geographical distribution records for 5 Caragana species. Through principal component analysis and Pearson correlation analysis, 11 environmental variables were identified. We employed the maximum entropy (MaxEnt) model and utilized the current and future climate dataset from 2041 to 2060 based on two extreme climate scenarios (RCP2.6 and RCP8.5) and atmospheric circulation models (BCC_CSM1.1 and IPSLCM5A-LR) to assess the potential distribution patterns and dynamic change with global warming. The results showed the following: (1) Currently, the five Caragana species are mainly distributed in the central and western parts of the Inner Mongolia Autonomous Region, Mongolia, and the southern parts of Russia. (2) In the future, the habitable zone of C. microphylla and C. korshinskii will expand gradually, while the distribution probability of C. stenophylla, C. tibetica, and C. pygmaea will shrink significantly in 60-80% of the area, and the habitable area will fluctuate sharply. (3) The range of the five species of Caragana expansion area is projected to be 1229.43×106 km2-1412.32×106 km2, with the suitable habitats expected to extend northward in the future, primarily concentrated in central Mongolia and around Lake Baikal in Russia. This research provides guidance for protecting grassland resources and ensuring sustainable development under shrub encroachment.
Subject(s)
Caragana , Ecosystem , Environmental Monitoring , Computer Simulation , ChinaABSTRACT
Tetrabromobisphenol A (TBBPA), a commonly utilized brominated flame retardant, is found in many types of abiotic and biotic matrices. TBBPA can increase oxidative stress, disrupt the endocrine system, cause neurodevelopmental disorders and activate peroxisome proliferator-activated receptors to modulate lipid deposits in aquatic animals. However, the toxic mechanism of TBBPA on the gut microbiota and intestinal health remains unclear. Apostichopus japonicus is an ideal model for studying the relationship between environmental contaminants and intestinal health due to its unique capacity for evisceration and quickly regenerated intestine. In the present study, we investigated the toxic mechanism of TBBPA on the gut microbiota and intestinal health in the regenerated intestine of A. japonicus. The results show that TBBPA exposure decreased the health of the regenerated intestine and the enzymatic activities, alpha diversity indices, and the relative abundance of the gut microbiota. Transcriptome analysis shows that TBBPA exposure affected lipid metabolism via the PPAR signaling pathway during the process of intestinal regeneration in A. japonicus, suggesting that TBBPA exposure can affect the composition and function of the gut microbiota and intestinal health in the regenerated intestine of A. japonicus. These results provide a basis for further research on the potential toxicity of TBBPA to the intestinal health in animals.
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Background: Persons living in sub-Saharan Africa (SSA) face disproportionate risk from overlapping epidemics of HIV and bacterial sexually transmitted infections (STIs). Pre-exposure prophylaxis (PrEP) for prevention is gradually being scaled up globally including in several settings in SSA, which represents a key opportunity to integrate STI services with HIV pre-exposure prophylaxis (PrEP). However, there is limited literature on how to successfully integrate these services, particularly in the SSA context. Prior studies and reviews on STI and PrEP services have largely focused on high income countries. Methods: We conducted a scoping review of prior studies of integration of STI and PrEP services in SSA. We searched PubMed, EMBASE, Cochrane, and CINAHL, in addition to grey literature to identify studies that were published between January 2012 and December 2022, and which provided STI and PrEP services in SSA, with or without outcomes reported. Citations and abstracts were reviewed by two reviewers for inclusion. Full texts were then retrieved and reviewed in full by two reviewers. Results: Our search strategy yielded 1951 records, of which 250 were retrieved in full. Our final review included 61 reports of 45 studies. Most studies were conducted in Southern (49.2%) and Eastern (24.6%) Africa. Service settings included public health clinics (26.2%), study clinics (23.0%), sexual and reproductive care settings (23.0%), maternal and child health settings (8.2%), community based services (11.5%), and mobile clinics (3.3%). A minority (11.4%) of the studies described only syndromic STI management while most (88.6%) included some form of etiological laboratory STI diagnosis. STI testing frequency ranged from baseline testing only to monthly screening. Types of STI tested for was also variable. Few studies reported outcomes related to implementation of STI services. There were high rates of curable STIs detected by laboratory testing (baseline genitourinary STI rates ranged from 5.6-30.8% for CT, 0.0-11.2% for GC, and 0.4-8.0% for TV). Discussion: Existing studies have implemented a varied range of STI services along with PrEP. This range reflects the lack of specific guidance regarding STI services within PrEP programs. However, there was limited evidence regarding implementation strategies for integration of STI and PrEP services in real world settings.
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Glioma is one of the most serious central nervous system diseases, with high mortality and poor prognosis. Despite the continuous development of existing treatment methods, the median survival time of glioma patients is still only 15 months. The main treatment difficulties are the invasive growth of glioma and the obstruction of the blood-brain barrier (BBB) to drugs. With rapid advancements in nanotechnology, inorganic nanoparticles (INPs) have shown favourable application prospects in the diagnosis and treatment of glioma. Due to their extraordinary intrinsic features, INPs can be easily fabricated, while doping with other elements and surface modification by biological ligands can be used to enhance BBB penetration, targeted delivery and biocompatibility. Guided glioma theranostics with INPs can improve and enhance the efficacy of traditional methods such as chemotherapy, radiotherapy and gene therapy. New strategies, such as immunotherapy, photothermal and photodynamic therapy, magnetic hyperthermia therapy, and multifunctional inorganic nanoplatforms, have also been facilitated by INPs. This review emphasizes the current state of research and clinical applications of INPs, including glioma targeting and BBB penetration enhancement methods, in vivo and in vitro biocompatibility, and diagnostic and treatment strategies. As such, it provides insights for the development of novel glioma treatment strategies.
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Introduction: Gendered power inequalities impact adolescent girls' and young women's (AGYW) sexual and reproductive health (SRH) outcomes. We investigated the influence of sexual relationship power on AGYW's SRH outcomes, including HIV pre-exposure prophylaxis (PrEP) persistence. Methods: The POWER study in Kisumu, Kenya, and Cape Town and Johannesburg, South Africa provided PrEP to 2,550 AGYW (aged 16-25). AGYW's perceived power in their primary sexual relationship was measured among the first 596 participants enrolled using the Sexual Relationship Power Scale's (SRPS) relationship control sub-scale. Multivariable regression was used to test for (1) key sociodemographic and relationship characteristics associated with relationship power; and (2) the association of relationship power with SRH outcomes including PrEP persistence. Results: In this cohort, the mean SRPS score was 2.56 (0.49), 542 (90.9%) initiated PrEP; 192 (35.4%) persisted with PrEP at 1 month of which 46 (24.0% of 192) persisted at 6 months. SRPS were significantly lower among AGYW who cohabited with their sex partner (-0.14, 95% CI: -0.24 to -0.04, p = 0.01), or had ≥1 sex partner (-0.10, 95% CI: -0.19 to -0.00, p = 0.05). AGYW with lower SRPS were more likely to not know their partner's HIV status (aOR 2.05, 95% CI: 1.27 to 3.33, p < 0.01), but SRPS was not associated with PrEP persistence, STI infection, condom, or hormonal contraception use. Discussion: AGYW's reasons for initiating PrEP and reasons for continuously using PrEP may be different. While low relationship power was associated with perceived HIV vulnerability, AGYW's PrEP persistence may be influenced by more than relationship power.
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Mutation breeding is a significant means of increasing breeding efficiency and accelerating breeding process. In present study, we explored a new method for mutations inducing in rice (Oryza sativa L.) by using direct current electrophoresis bath (DCEB). The results showed that 20 mM NaCl solution is the optimal buffer, and the mortality of rice seeds followed an upward trend with increasing voltage and processing time of DCEB. By exploring the mutagenic effects of γ-irradiation and DCEB on seed vigor and physiological damages, we found that the physiological damages induced by DCEB on seed vigor were significant compared with that by γ-irradiation. We screened two mutants with low filled grain percentage and one mutant with abnormal hull from the M2 generations. These three mutants were confirmed to be authentic mutants based on 48 SSR markers followed by the protocol NY/T 1433-2014. Whole-genome resequencing detected a total of 503 and 537 polymorphisms in the two mutants, respectively, and the DCEB mutagenesis induced mainly InDel variants, while the exon region of mutant genes occupied a large proportion, especially the SNP variants, which occupied about 20% of the mutation sites in the exon region.
Subject(s)
Oryza , Oryza/genetics , Oryza/radiation effects , Mutagens , Plant Breeding , Mutation , Mutagenesis/genetics , Seeds/geneticsABSTRACT
Although several regulators associated with purple traits in rice have been identified, the genetic basis of the purple sheath remains unclear. In the present study, F2-1 and F2-2 populations were constructed using purple sheath (H93S) and green sheath (R1173 and YHSM), respectively. In order to identify QTL loci in purple sheaths, BSA analyses were performed on the two F2 populations. A crucial QTL for purple sheath was identified, tentatively named qPLSr6, and was located in the 4.61 Mb to 6.03 Mb region of chromosome 6. Combined with expression pattern analysis of candidate genes, LOC_Os06g10350 (OsC1PLSr) was suggested as a candidate gene. The homozygous mutant KO-1 and KO-2 created through CRISPR/Cas9 editing, lost their purple leaf sheath. The RT-PCR revealed that OsC1PLSr, anthocyanin synthase (ANS), diflavonol-4-reductase (DFR), flavanone-3-hydroxylase (F3H), and flavanone-3'-hydroxylase (F3'H) expression levels were dramatically down-regulated in the mutants. The yeast report system indicated that the 145-272 aa region at the C-terminal of OsC1PLSr is a positive transcriptional activation domain. The results indicated that OsC1PLSr synthesized anthocyanins by regulating the expression of ANS, DFR, F3H, and F3'H. This study provides new insights into the genetic basis of the purple sheath.
Subject(s)
Flavanones , Oryza , Transcription Factors/genetics , Transcription Factors/metabolism , Anthocyanins/metabolism , Oryza/genetics , Oryza/metabolism , Gene Expression Regulation, Plant , Plant Leaves/genetics , Plant Leaves/metabolism , Oxidoreductases/metabolism , Mixed Function Oxygenases/genetics , Flavanones/metabolism , Plant Proteins/genetics , Plant Proteins/metabolismABSTRACT
BACKGROUND: Telomere dysfunction has been reported to be directly involved in carcinogenesis owing to chromosomal instability and immortalization; however, the clinicopathological significance of telomeres remains controversial. We have shown that telomere shortening occurs in normal-appearing duct cells at initiation and then continues during the progression of pancreatic cancer. In this study, we determined the clinicopathological and prognostic value of telomere length (TL) in cancer progression. METHODS: TL in both cancer cells and cancer-associated fibroblasts (CAFs) was analyzed by high-throughput quantitative fluorescence in situ hybridization using a previously reported cohort comprising 1434 cases of adenocarcinoma (ADC), squamous cell carcinoma (SCC), adenosquamous carcinoma, hepatocellular carcinoma, and renal cell carcinoma (RCC), which are known cancers with a statistically significantly low incidence of alternative lengthening of telomeres. Cases were divided into 2 groups as follows: longer and shorter telomeres, according to the median TL of cancer cells and CAFs. The statistical significance of TL in cancer cells and CAFs on clinicopathological characteristics and prognosis was analyzed. RESULTS: There was a close association between TL in cancer cells and CAFs. Longer telomeres in cancer cells and CAFs were associated with aggressive features such as advanced stage, high mitosis score and nuclear score, poorly differentiated cancer, and desmoplastic stroma in ADC. Furthermore, a longer TL was an independent prognostic factor for ADC, SCC, and RCC. CONCLUSIONS: Longer telomeres are associated with worse prognosis in ADC, SCC, and RCC. Thus, TL is a novel biomarker for the diagnosis of aggressive cancers with poor prognoses.
Subject(s)
Cancer-Associated Fibroblasts , Carcinoma, Renal Cell , Carcinoma, Squamous Cell , Kidney Neoplasms , Liver Neoplasms , Humans , Cancer-Associated Fibroblasts/pathology , In Situ Hybridization, Fluorescence , Prognosis , Telomere Shortening , Telomere , Carcinoma, Squamous Cell/pathology , Liver Neoplasms/pathology , Telomere HomeostasisABSTRACT
In this study, accumulated fermentable sugars from biosaccharified corn straw were used to generate methane through anaerobic digestion (AD). The results showed that reducing sugars from biosaccharification expanded corn straw (BECS) treated with Clostridium thermocellum XF811 accumulated with yields of 94.9 mg/g. The BECS used for AD was converted into a high methane yield (7436 mL), which was 49.3 % higher than that of expanded corn straw (ECS). High-throughput microbial analysis suggested that Methanoculleus and Methanobacterium greatly contributed to the high methane yield. Industrial experiments demonstrated that the methane production from BECS by AD was 72,955 m3, which increased by 13.2 % compared to that from ECS. Biosaccharification pretreatment accelerated ECS destruction and accumulated sugars, thereby increasing methane yields. This study provides a strategy for producing clean energy from lignocellulose biomass.
Subject(s)
Methane , Zea mays , Anaerobiosis , Biomass , Sugars , BiofuelsABSTRACT
The loss of the shattering ability is one of the key events in rice domestication. The strength of the seed shattering ability is closely related to the harvest yield and the adaptability of modern mechanical harvesting methods. In this study, using a population of 587 natural rice cultivars, quantitative trait loci associated with seed shattering were detected by genome-wide association studies (GWASs). We consider the quantitative trait loci (QTLs) qBTS1 and qBTS3 to be the key loci for seed shattering in rice. Additionally, the abscission zone (AZ) and nonabscission zone (NAZ) of materials with a loss of shattering (DZ129) and easy shattering (W517) were subjected to RNA-Seq, and high-quality differential expression profiles were obtained. The AZ-specific differentially expressed genes (DEGs) of W517 were significantly enriched in plant hormone signal transduction, while the AZ-specific DEGs of DZ129 were enriched in phenylpropanoid biosynthesis. We identified candidate genes for the lignin-associated laccase precursor protein (LOC_Os01g63180) and the glycoside hydrolase family (LOC_Os03g14210) in the QTLs qBTS1 (chromosome 1) and qBTS3 (chromosome 3), respectively. In summary, our findings lay the foundation for the further cloning of qBTS1 and qBTS3, which would provide new insights into seed shattering in rice.
Subject(s)
Oryza , Oryza/genetics , Genome-Wide Association Study , RNA-Seq , Phenotype , Seeds/geneticsABSTRACT
INTRODUCTION: HIV incidence remains high among African adolescent girls and young women (AGYW). The primary objective of this study is to assess pre-exposure prophylaxis (PrEP) initiation, use, persistence and HIV acquisition among African AGYW offered PrEP in order to inform PrEP scale-up. METHODS: POWER was a prospective implementation science evaluation of PrEP delivery for sexually active HIV-negative AGYW ages 16-25 in family planning clinics in Kisumu, Kenya and youth and primary healthcare clinics in Cape Town and Johannesburg, South Africa. Follow-up visits occurred at month 1 and quarterly for up to 36 months. PrEP users were defined based on the month 1 refill. PrEP persistence through month 6 was assessed using Kaplan-Meier survival analysis among AGYW with a month 1 visit, defining non-persistence as an ≥15 day gap in PrEP availability for daily dosing. PrEP execution was evaluated in a subset with PrEP supply from the prior visit sufficient for daily dosing by measuring blood tenofovir diphosphate (TFV-DP) levels. RESULTS: From June 2017 to September 2020, 2550 AGYW were enrolled (1000 in Kisumu, 787 in Cape Town and 763 in Johannesburg). Median age was 21 years, 66% had a sexual partner of unknown HIV status, and 29% had chlamydia and 10% gonorrhoea. Overall, 2397 (94%) initiated PrEP and 749 (31%) had a refill at 1 month. Of AGYW who could reach 6 months of post-PrEP initiation follow-up, 128/646 (20%) persisted with PrEP for 6 months and an additional 92/646 (14%) had a gap and restarted PrEP. TFV-DP levels indicated that 47% (91/193) took an average of ≥4 doses/week. Sixteen HIV seroconversions were observed (incidence 2.2 per 100 person-years, 95% CI 1.2, 3.5); 13 (81%) seroconverters either did not have PrEP dispensed in the study interval prior to seroconversion or TFV-DP levels indicated <4 doses/week in the prior 6 weeks. CONCLUSIONS: In this study of PrEP integration with primary care and reproductive health services for African AGYW, demand for PrEP was high. Although PrEP use decreased in the first months, an important fraction used PrEP through 6 months. Strategies are needed to simplify PrEP delivery, support adherence and offer long-acting PrEP options to improve persistence and HIV protection.