The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance.

The maintenance of immunological tolerance requires the deletion of self-reactive T cells in the thymus. The expression of genes encoding tissue-specific antigens (TSAs) by thymic epithelial cells is critical for this process and depends on activity of the transcriptional regulator Aire; however, the molecular mechanisms Aire uses to target loci encoding TSAs are unknown. Here we identified two Aire-interacting proteins known to be involved in gene repression, ATF7ip and MBD1, that were required for Aire's targeting of loci encoding TSAs. Moreover, Mbd1(-/-) mice developed pathological autoimmunity and had a defect in Aire-dependent thymic expression of genes encoding TSAs, which underscores the importance of Aire's interaction with the ATF7ip-MBD1 protein complex in maintaining central tolerance.

Loss of Pde1 function acts as an evolutionary gateway to penicillin resistance in Streptococcus pneumoniae.

Streptococcus pneumoniae is a major human pathogen and rising resistance to ß-lactam antibiotics, such as penicillin, is a significant threat to global public health. Mutations occurring in the penicillin-binding proteins (PBPs) can confer high-level penicillin resistance but other poorly understood genetic factors are also important. Here, we combined strictly controlled laboratory experiments and population analyses to identify a new penicillin resistance pathway that is independent of PBP modification. Initial laboratory selection experiments identified high-frequency pde1 mutations conferring S. pneumoniae penicillin resistance. The importance of variation at the pde1 locus was confirmed in natural and clinical populations in an analysis of >7,200 S. pneumoniae genomes. The pde1 mutations identified by these approaches reduce the hydrolytic activity of the Pde1 enzyme in bacterial cells and thereby elevate levels of cyclic-di-adenosine monophosphate and penicillin resistance. Our results reveal rapid de novo loss of function mutations in pde1 as an evolutionary gateway conferring low-level penicillin resistance. This relatively simple genomic change allows cells to persist in populations on an adaptive evolutionary pathway to acquire further genetic changes and high-level penicillin resistance.

Exploring switch II pocket conformation of KRAS(G12D) with mutant-selective monobody inhibitors.

The G12D mutation is among the most common KRAS mutations associated with cancer, in particular, pancreatic cancer. Here, we have developed monobodies, small synthetic binding proteins, that are selective to KRAS(G12D) over KRAS(wild type) and other oncogenic KRAS mutations, as well as over the G12D mutation in HRAS and NRAS. Crystallographic studies revealed that, similar to other KRAS mutant-selective inhibitors, the initial monobody bound to the S-II pocket, the groove between switch II and α3 helix, and captured this pocket in the most widely open form reported to date. Unlike other G12D-selective polypeptides reported to date, the monobody used its backbone NH group to directly recognize the side chain of KRAS Asp12, a feature that closely resembles that of a small-molecule inhibitor, MTRX1133. The monobody also directly interacted with H95, a residue not conserved in RAS isoforms. These features rationalize the high selectivity toward the G12D mutant and the KRAS isoform. Structure-guided affinity maturation resulted in monobodies with low nM KD values. Deep mutational scanning of a monobody generated hundreds of functional and nonfunctional single-point mutants, which identified crucial residues for binding and those that contributed to the selectivity toward the GTP- and GDP-bound states. When expressed in cells as genetically encoded reagents, these monobodies engaged selectively with KRAS(G12D) and inhibited KRAS(G12D)-mediated signaling and tumorigenesis. These results further illustrate the plasticity of the S-II pocket, which may be exploited for the design of next-generation KRAS(G12D)-selective inhibitors.

Bi-allelic loss-of-function variants in TMEM147 cause moderate to profound intellectual disability with facial dysmorphism and pseudo-Pelger-Huët anomaly.

The transmembrane protein TMEM147 has a dual function: first at the nuclear envelope, where it anchors lamin B receptor (LBR) to the inner membrane, and second at the endoplasmic reticulum (ER), where it facilitates the translation of nascent polypeptides within the ribosome-bound TMCO1 translocon complex. Through international data sharing, we identified 23 individuals from 15 unrelated families with bi-allelic TMEM147 loss-of-function variants, including splice-site, nonsense, frameshift, and missense variants. These affected children displayed congruent clinical features including coarse facies, developmental delay, intellectual disability, and behavioral problems. In silico structural analyses predicted disruptive consequences of the identified amino acid substitutions on translocon complex assembly and/or function, and in vitro analyses documented accelerated protein degradation via the autophagy-lysosomal-mediated pathway. Furthermore, TMEM147-deficient cells showed CKAP4 (CLIMP-63) and RTN4 (NOGO) upregulation with a concomitant reorientation of the ER, which was also witnessed in primary fibroblast cell culture. LBR mislocalization and nuclear segmentation was observed in primary fibroblast cells. Abnormal nuclear segmentation and chromatin compaction were also observed in approximately 20% of neutrophils, indicating the presence of a pseudo-Pelger-Huët anomaly. Finally, co-expression analysis revealed significant correlation with neurodevelopmental genes in the brain, further supporting a role of TMEM147 in neurodevelopment. Our findings provide clinical, genetic, and functional evidence that bi-allelic loss-of-function variants in TMEM147 cause syndromic intellectual disability due to ER-translocon and nuclear organization dysfunction.

Inhibition of RAS-driven signaling and tumorigenesis with a pan-RAS monobody targeting the Switch I/II pocket.

RAS mutants are major therapeutic targets in oncology with few efficacious direct inhibitors available. The identification of a shallow pocket near the Switch II region on RAS has led to the development of small-molecule drugs that target this site and inhibit KRAS(G12C) and KRAS(G12D). To discover other regions on RAS that may be targeted for inhibition, we have employed small synthetic binding proteins termed monobodies that have a strong propensity to bind to functional sites on a target protein. Here, we report a pan-RAS monobody, termed JAM20, that bound to all RAS isoforms with nanomolar affinity and demonstrated limited nucleotide-state specificity. Upon intracellular expression, JAM20 potently inhibited signaling mediated by all RAS isoforms and reduced oncogenic RAS-mediated tumorigenesis in vivo. NMR and mutation analysis determined that JAM20 bound to a pocket between Switch I and II, which is similarly targeted by low-affinity, small-molecule inhibitors, such as BI-2852, whose in vivo efficacy has not been demonstrated. Furthermore, JAM20 directly competed with both the RAF(RBD) and BI-2852. These results provide direct validation of targeting the Switch I/II pocket for inhibiting RAS-driven tumorigenesis. More generally, these results demonstrate the utility of tool biologics as probes for discovering and validating druggable sites on challenging targets.

A perspective on the metastasis suppressor field.

Metastasis is the leading cause of cancer patient mortality. Metastasis suppressors are genes that, upon reexpression in metastatic tumor cells to levels observed in their nonmetastatic counterparts, significantly reduce metastasis without affecting the growth of the primary tumor. Analysis of > 30 metastasis suppressors revealed complex mechanisms of action that include multiple signaling pathways, transcriptional patterns, posttranscriptional regulatory mechanisms, and potential contributions of genomic stability. Clinical testing of strategies to re-establish a validated metastasis suppressor pathway in tumors is best directed to the adjuvant setting, with the goal of inhibiting the outgrowth of occult micrometastases.

Rational Design Strategy for High-Valence Metal-Driven Electronically Modulated High-Entropy Co-Ni-Fe-Cu-Mo (Oxy)Hydroxide as Superior Multifunctional Electrocatalysts.

Creating durable and efficient multifunctional electrocatalysts capable of high current densities at low applied potentials is crucial for widespread industrial use in hydrogen production. Herein, a Co-Ni-Fe-Cu-Mo (oxy)hydroxide electrocatalyst with abundant grain boundaries on nickel foam using a scalable coating method followed by chemical precipitation is synthesized. This technique efficiently organizes hierarchical Co-Ni-Fe-Cu-Mo (oxy)hydroxide nanoparticles within ultrafine crystalline regions (<4 nm), enriched with numerous grain boundaries, enhancing catalytic site density and facilitating charge and mass transfer. The resulting catalyst, structured into nanosheets enriched with grain boundaries, exhibits superior electrocatalytic activity. It achieves a reduced overpotential of 199 mV at 10 mA cm2 current density with a Tafel slope of 48.8 mV dec1 in a 1 m KOH solution, maintaining stability over 72 h. Advanced analytical techniques reveal that incorporating high-valency copper and molybdenum elements significantly enhances lattice oxygen activation, attributed to weakened metal-oxygen bonds facilitating the lattice oxygen mechanism (LOM). Synchrotron radiation studies confirm a synergistic interaction among constituent elements. Furthermore, the developed high-entropy electrode demonstrates exceptional long-term stability under high current density in alkaline environments, showcasing the effectiveness of high-entropy strategies in advancing electrocatalytic materials for energy-related applications.

A review on the application of bioinformatics tools in food microbiome studies.

There is currently a transformed interest toward understanding the impact of fermentation on functional food development due to growing consumer interest on modified health benefits of sustainable foods. In this review, we attempt to summarize recent findings regarding the impact of Next-generation sequencing and other bioinformatics methods in the food microbiome and use prediction software to understand the critical role of microbes in producing fermented foods. Traditionally, fermentation methods and starter culture development were considered conventional methods needing optimization to eliminate errors in technique and were influenced by technical knowledge of fermentation. Recent advances in high-output omics innovations permit the implementation of additional logical tactics for developing fermentation methods. Further, the review describes the multiple functions of the predictions based on docking studies and the correlation of genomic and metabolomic analysis to develop trends to understand the potential food microbiome interactions and associated products to become a part of a healthy diet.

The gut microbiome in the fight against obesity: The potential of dietary factors.

Obesity as a global public health burden has experienced a drastic growing trend recently. The management of obesity is challenging because of its complex etiology, and various factors are involved in its development, such as genetic and environmental factors. Different approaches are available to treat and/or manage obesity, including diet, physical activity, lifestyle changes, medications, and surgery. However, some of these approaches have inherent limitations and are closely associated with adverse effects. Therefore, probing into a novel/safe approach to treat and/or manage obesity is of fundamental importance. One such approach gaining renewed interest is the potential role of gut microbiota in obesity and its effectiveness in treating this condition. However, there is a dearth of comprehensive compilation of data on the potential role of the gut microbiome in obesity, particularly regarding dietary factors as a therapeutic approach. Therefore, this review aims to provide an updated overview of the role of gut microbiota in obesity, further highlighting the importance of dietary factors, particularly diet, prebiotics, and probiotics, as potential complementary and/or alternative therapeutic options. Moreover, the association of gut microbiota with obese or lean individuals has also been discussed.

Attenuation of Streptozotocin-Induced Diabetic Neuropathic Allodynia by Flavone Derivative Through Modulation of GABA-ergic Mechanisms and Endogenous Biomarkers.

Diabetic neuropathic pain is one of the most devasting disorders of peripheral nervous system. The loss of GABAergic inhibition is associated with the development of painful diabetic neuropathy. The current study evaluated the potential of 3-Hydroxy-2-methoxy-6-methyl flavone (3-OH-2'MeO6MF), to ameliorate peripheral neuropathic pain using an STZ-induced hyperglycemia rat model. The pain threshold was assessed by tail flick, cold, mechanical allodynia, and formalin test on days 0, 14, 21, and 28 after STZ administration accompanied by evaluation of several biochemical parameters. Administration of 3-OH-2'-MeO6MF (1,10, 30, and 100 mg/kg, i.p) significantly enhanced the tail withdrawal threshold in tail-flick and tail cold allodynia tests. 3-OH-2'-MeO6MF also increased the paw withdrawal threshold in mechanical allodynia and decreased paw licking time in the formalin test. Additionally, 3-OH-2'-MeO6MF also attenuated the increase in concentrations of myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), nitrite, TNF-α, and IL 6 along with increases in glutathione (GSH). Pretreatment of pentylenetetrazole (PTZ) (40 mg/kg, i.p.) abolished the antinociceptive effect of 3-OH-2'-MeO6MF in mechanical allodynia. Besides, the STZ-induced alterations in the GABA concentration and GABA transaminase activity attenuated by 3-OH-2'-MeO6MF treatment suggest GABAergic mechanisms. Molecular docking also authenticates the involvement of α2ß2γ2L GABA-A receptors and GABA-T enzyme in the antinociceptive activities of 3-OH-2'-MeO6MF.

An exploratory deep learning approach to investigate tuberculosis pathogenesis in nonhuman primate model: Combining automated radiological analysis with clinical and biomarkers data.

BACKGROUND: Tuberculosis (TB) kills approximately 1.6 million people yearly despite the fact anti-TB drugs are generally curative. Therefore, TB-case detection and monitoring of therapy, need a comprehensive approach. Automated radiological analysis, combined with clinical, microbiological, and immunological data, by machine learning (ML), can help achieve it. METHODS: Six rhesus macaques were experimentally inoculated with pathogenic Mycobacterium tuberculosis in the lung. Data, including Computed Tomography (CT), were collected at 0, 2, 4, 8, 12, 16, and 20 weeks. RESULTS: Our ML-based CT analysis (TB-Net) efficiently and accurately analyzed disease progression, performing better than standard deep learning model (LLM OpenAI's CLIP Vi4). TB-Net based results were more consistent than, and confirmed independently by, blinded manual disease scoring by two radiologists and exhibited strong correlations with blood biomarkers, TB-lesion volumes, and disease-signs during disease pathogenesis. CONCLUSION: The proposed approach is valuable in early disease detection, monitoring efficacy of therapy, and clinical decision making.

Engineering MPC-Assisted Heterojunctional Photo-Oxidation Tailored by Interfacial Design of a P-Modulated C3N4 Heterojunction for Improved Aerobic Alcohol Oxidation.

The creation of two-dimensional van der Waals (VDW) heterostructures is a sophisticated approach to enhancing photocatalytic efficiency. However, challenges in electron transfer at the interfaces often arise in these heterostructures due to the varied structures and energy barriers of the components involved. This study presents a novel method for constructing a VDW heterostructure by inserting a phosphate group between copper phthalocyanine (CuPc) and boron-doped, nitrogen-deficient graphitic carbon nitride (BCN), referred to as Cu/PO4-BCN. This phosphate group serves as a charge mediator, enabling effective charge transfer within the heterostructure, thus facilitating electron flow from BCN to CuPc upon activation. As a result, the photogenerated electrons are effectively utilized by the catalytic Cu2+ core in CuPc, achieving a conversion efficiency of 96% for benzyl alcohol (BA) and a selectivity of 98.8% for benzyl aldehyde (BAD) in the presence of oxygen as the sole oxidant and under illumination. Notably, the production rate of BAD is almost 8 times higher than that observed with BCN alone and remains stable over five cycles. The introduction of interfacial mediators to enhance electron transfer represents a pioneering and efficient strategy in the design of photocatalysts, enabling the proficient transformation of BA into valuable derivatives.

Dimensionally Intact Construction of Ultrathin S-Scheme CuFe2O4/ZnIn2S4 Heterojunctional Photocatalysts for CO2 Photoreduction.

The conversion of CO2 into carbon-neutral fuels such as methane (CH4) through selective photoreduction is highly sought after yet remains challenging due to the slow multistep proton-electron transfer processes and the formation of various C1 intermediates. This research highlights the cooperative interaction between Fe3+ and Cu2+ ions transitioning to Fe2+ and Cu+ ions, enhancing the photocatalytic conversion of CO2 to methane. We introduce an S-scheme heterojunction photocatalyst, CuFe2O4/ZnIn2S4, which demonstrates significant efficiency in CO2 methanation under light irradiation. The CuFe2O4/ZnIn2S4 heterojunction forms an internal electric field that aids in the mobility and separation of exciton carriers under a wide solar spectrum for exceptional photocatalytic performance. Remarkably, the optimal CuFe2O4/ZnIn2S4 heterojunction system achieved an approximately 68-time increase in CO2 conversion compared with ZnIn2S4 and CuFe2O4 nanoparticles using only pure water, with nearly complete CO selectivity and yields of CH4 and CO reaching 172.5 and 202.4 µmol g-1 h-1, respectively, via a 2-electron oxygen reduction reaction (ORR) process. The optimally designed CuFe2O4/ZnIn2S4 heterojunctional system achieved approximately 96% conversion of BA and 98.5% selectivity toward benzaldehyde (BAD). Additionally, this photocatalytic system demonstrated excellent cyclic stability and practical applicability. The photogenerated electrons in the CuFe2O4 conduction band enhance the reduction of Fe3+/Cu2+ to Fe2+/Cu+, creating a microenvironment conducive to CO2 reduction to CO and CH4. Simultaneously, the appearance of holes in the ZnIn2S4 valence band facilitates water oxidation to O2. The synergistic function within the CuFe2O4/ZnIn2S4 heterojunction plays a pivotal role in facilitating charge transfer, accelerating water oxidation, and thereby enhancing CO2 reduction kinetics. This study offers valuable insights and a strategic framework for designing efficient S-scheme heterojunctions aimed at achieving carbon neutrality through solar fuel production.

Optical transparency in 2D ferromagnetic WSe2/1T-VSe2/WSe2multilayer with strain induced large anomalous Nernst conductivity.

Transparent two-dimensional (2D) magnetic materials may bring intriguing features and are indispensable for transparent electronics. However, it is rare to find both optical transparency and room-temperature ferromagnetism simultaneously in a single 2D material. Herein, we explore the possibility of both these features in 2D WSe2/1T-VSe2(1ML)/WSe2and WSe2/1T-VSe2(2ML)/WSe2heterostructures by taking one monolayer (1ML) and two monolayers (2ML) of 1T-VSe2using first-principles calculations. Further, we investigate anomalous Hall conductivity (AHC) and anomalous Nernst conductivity (ANC) using a maximally localized Wannier function. The WSe2/1T-VSe2(1ML)/WSe2and WSe2/1T-VSe2(2ML)/WSe2systems show Curie temperatures of 328 and 405 K. Under biaxial compressive strain, the magnetic anisotropy of both systems is switched from in-plane to out-of-plane. We find a large AHC of 1.51 e2/h and 3.10 e2/h in the electron-doped region for strained WSe2/1T-VSe2(1ML)/WSe2and WSe2/1T-VSe2(2ML)/WSe2systems. Furthermore, we obtain a giant ANC of 3.94 AK-1m-1in a hole-doped strained WSe2/1T-VSe2(2ML)/WSe2system at 100 K. Both WSe2/1T-VSe2(1ML)/WSe2and WSe2/1T-VSe2(2ML)/WSe2are optically transparent in the visible ranges with large refractive indices of 3.2-3.4. Our results may suggest that the WSe2/1T-VSe2/WSe2structure possesses multifunctional physical properties and these features can be utilized for spintronics and optoelectronics device applications such as magnetic sensors, memory devices, and transparent magneto-optic devices at room temperature.

The interplay of PTEN and AKT nexus in breast cancer: a molecular perspective.

BACKGROUND: Breast cancer is a highly prevalent and life-threatening ailment that is commonly detected among the females. The downregulation of PTEN in breast cancer is associated with a poor prognosis, aggressive tumor type, and metastasis to lymph nodes, as it activates the pro-survival pathway PI3K/AKT, which is considered the ultimate proliferative pathway. MATERIAL AND METHODS: The mRNA expression of PTEN and AKT genes was investigated using RT-qPCR and TaqMan primer probe chemistry. Moreover DNA was also isolated from the same tissue samples and exonic regions of both genes were amplified for mutational analysis. The proteins expression of PTEN and AKT from seven human breast cancer cell lines was checked through western blot experiments. RESULT: The study revealed a decrease in PTEN expression in 73.3% of the samples, whereas an increase in AKT expression in 40% of samples was observed when compared to the distant normal breast tissue. Conversely, the remaining 60% of samples exhibited a decrease in AKT mRNA expression. There was no observed alteration in the genetic sequence of AKT and PTEN within the targeted amplified regions of breast cancer samples. The high levels of PTEN protein in T-47D and MDA-MB-453 resulted in a lower p-AKT. Two cell lines ZR-75-1 and MDA-MB-468 appeared to be PTEN negative on western blot but mRNA was detected on RT-qPCR. CONCLUSION: In breast cancer the status/expression of PTEN & AKT at mRNA and protein level might be obliging in forecasting the path of disease progression, treatment and prognosis.

Thymic tuft cells promote an IL-4-enriched medulla and shape thymocyte development.

The thymus is responsible for generating a diverse yet self-tolerant pool of T cells1. Although the thymic medulla consists mostly of developing and mature AIRE+ epithelial cells, recent evidence has suggested that there is far greater heterogeneity among medullary thymic epithelial cells than was previously thought2. Here we describe in detail an epithelial subset that is remarkably similar to peripheral tuft cells that are found at mucosal barriers3. Similar to the periphery, thymic tuft cells express the canonical taste transduction pathway and IL-25. However, they are unique in their spatial association with cornified aggregates, ability to present antigens and expression of a broad diversity of taste receptors. Some thymic tuft cells pass through an Aire-expressing stage and depend on a known AIRE-binding partner, HIPK2, for their development. Notably, the taste chemosensory protein TRPM5 is required for their thymic function through which they support the development and polarization of thymic invariant natural killer T cells and act to establish a medullary microenvironment that is enriched in the type 2 cytokine, IL-4. These findings indicate that there is a compartmentalized medullary environment in which differentiation of a minor and highly specialized epithelial subset has a non-redundant role in shaping thymic function.

The impact of acute kidney injury stages on the outcomes of veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: Although acute kidney injury (AKI) has been established as an independent risk factor for in-hospital mortality for patients on veno-arterial (V-A) extracorporeal membranous oxygenation (ECMO), the impact of Kidney Disease Improving Global Outcomes (KDIGO) stages of AKI has yet to be elucidated as a risk factor. METHODS: We conducted a retrospective analysis of patient outcomes based on KDIGO stages of AKI at a single institution. The analysis was a cohort of 179 patients; 66 without AKI, 19 with stage 1 AKI, 18 with stage 2 AKI, and 76 with stage 3 AKI. RESULTS: Every 1-year increase in age was associated with 4% increased odds of mortality at 30 days (95% confidence interval [CI] 1.01, 1.07; p = 0.004). The presence of AKI at any stage was associated with 59% increased odds of 30-day mortality (95% CI 0.81, 3.10; p = 0.176). The presence of stage 1 AKI was associated with a 5% decreased odds of 30-day mortality (95% CI 0.32, 2.89). The presence of stage 2 AKI (odds ratio [OR] 2.29, 95% CI 0.69, 7.55; p = 0.173) and stage 3 AKI (OR 1.68, 95% CI 0.81, 3.46; p = 0.164) was associated with increased odds of 30-day mortality. CONCLUSION: Based on our single-center study, higher KDIGO stages of AKI likely have increased odds of mortality at 30 days. Larger studies are needed to confirm these findings.

Community cervical cancer screening and precancer risk in women living with HIV in Jos Nigeria.

BACKGROUND: High HIV prevalence, and lack of organized screening for the indigent population receiving care and treatment within HIV clinics in low-resource settings increases cervical cancer incidence. We sought to determine predictors of cervical precancer in women living with HIV and receiving cervical cancer screening in Jos, Nigeria. METHODS: A cross-sectional study of women living with HIV and receiving care and treatment in adult HIV/AIDS clinics in Jos-Metropolis, Nigeria between June 2020 and April 2023. Ethical approvals were obtained from the ethics committee in Jos, Nigeria and Northwestern University IRB, USA. Informed consent was obtained from eligible participants, and data on socio-demographics, cancer risk factors, and cytology reports were collected. The outcome variables were cervical precancer lesions. The independent variables were prior Pap smear status, socio-demographics, income, educational, and other reproductive health factors. Descriptive statistics was done to obtain means ± sd, frequencies, and percentages for the variables. Univariate and bivariate analyses were done to determine predictors of cervical dysplasia. Analyses were performed using R software. RESULTS: Of 957 women screened, 570 were living with HIV and 566 women had cytology report and were included in the final analysis. The mean age was 45.08 ± 8.89 years and 81.6% had no prior evidence of Pap test (under-screened). Prevalence of cervical dysplasia was 24% (mild and severe dysplasia were 12.9% and 11.1%, respectively). Age above 45 years (aOR = 3.48, p = 0.009), postmenopausal status (aOR = 7.69, p = 0.000), and women with no history of prior IUCD use (aOR = 5.94, p = 0.0001), were predictors for severe dysplasia. Women who had history of STI (aOR = 0.17, p = 0.000), prior use of IUCD (aOR = 0.32, p = 0.004), prior use of condom (aOR = 2.50, p = 0.003) and had co-morbidities (aOR = 0.46, p = 0.009) were more likely to have had a Pap test in the past. CONCLUSIONS: The majority of indigent women receiving care at HIV clinics had their first Pap test screening, and lack of organized screening among older and post-menopausal women with HIV, puts women at a higher risk of developing severe cervical precancer lesions.

Tuning active sites on biochars for remediation of mercury-contaminated soil: A comprehensive review.

Mercury (Hg) contamination is acknowledged as a global issue and has generated concerns globally due to its toxicity and persistence. Tunable surface-active sites (SASs) are one of the key features of efficient BCs for Hg remediation, and detailed documentation of their interactions with metal ions in soil medium is essential to support the applications of functionalized BC for Hg remediation. Although a specific active site exhibits identical behavior during the adsorption process, a systematic documentation of their syntheses and interactions with various metal ions in soil medium is crucial to promote the applications of functionalized biochars in Hg remediation. Hence, we summarized the BC's impact on Hg mobility in soils and discussed the potential mechanisms and role of various SASs of BC for Hg remediation, including oxygen-, nitrogen-, sulfur-, and X (chlorine, bromine, iodine)- functional groups (FGs), surface area, pores and pH. The review also categorized synthesis routes to introduce oxygen, nitrogen, and sulfur to BC surfaces to enhance their Hg adsorptive properties. Last but not the least, the direct mechanisms (e.g., Hg- BC binding) and indirect mechanisms (i.e., BC has a significant impact on the cycling of sulfur and thus the Hg-soil binding) that can be used to explain the adverse effects of BC on plants and microorganisms, as well as other related consequences and risk reduction strategies were highlighted. The future perspective will focus on functional BC for multiple heavy metal remediation and other potential applications; hence, future work should focus on designing intelligent/artificial BC for multiple purposes.

Exploring the potential of machine learning in gynecological care: a review.

Gynecological health remains a critical aspect of women's overall well-being, with profound implications for maternal and reproductive outcomes. This comprehensive review synthesizes the current state of knowledge on four pivotal aspects of gynecological health: preterm birth, breast cancer and cervical cancer and infertility treatment. Machine learning (ML) has emerged as a transformative technology with the potential to revolutionize gynecology and women's healthcare. The subsets of AI, namely, machine learning (ML) and deep learning (DL) methods, have aided in detecting complex patterns from huge datasets and using such patterns in making predictions. This paper investigates how machine learning (ML) algorithms are employed in the field of gynecology to tackle crucial issues pertaining to women's health. This paper also investigates the integration of ultrasound technology with artificial intelligence (AI) during the initial, intermediate, and final stages of pregnancy. Additionally, it delves into the diverse applications of AI throughout each trimester.This review paper provides an overview of machine learning (ML) models, introduces natural language processing (NLP) concepts, including ChatGPT, and discusses the clinical applications of artificial intelligence (AI) in gynecology. Additionally, the paper outlines the challenges in utilizing machine learning within the field of gynecology.