Oncolytic virotherapy stimulates anti­tumor immune response and demonstrates activity in advanced sarcoma: Report of two cases.

Sarcoma is derived from mesenchymal neoplasms and has numerous subtypes, accounting for 1% of all adult malignancies and 15% of childhood malignancies. The prognosis of metastatic or recurrent sarcoma remains poor. The current study presents two cases of sarcoma enrolled in a phase I dose escalation trial for solid tumor, who had previously failed all standard therapies. These patients were treated with VG161, an immune-stimulating herpes simplex virus type 1 oncolytic virus with payloads of IL-12, IL-15 and IL-15 receptor α unit, and a programmed cell death 1 (PD-1)/PD-1 ligand 1 blocking peptide. Both cases demonstrated stable disease as the best response, accompanied by a noteworthy prolongation of progression-free survival (11.8 months for chondrosarcoma and 11.9 months for soft tissue sarcoma, respectively) at a dose of 2.5×108 PFU/cycle. In addition, the treatment led to the activation of anti-cancer immunity, as evident from cytokine, lymphocyte subset and related pathway analyses of peripheral blood and/or tumor biopsy samples. These promising results suggest that VG161 monotherapy holds promise as an effective treatment for sarcoma and warrants further investigation through clinical trials. The two reported patients were part of a phase I clinical trial conducted and registered on the Australian New Zealand Clinical Trials Registry in Australia (registration no. ACTRN12620000244909; registration date, 26 February, 2020).

Application and effect of tension-reducing suture in surgical treatment of hypertrophic scar.

PURPOSE: To investigate the application and effectiveness of tension-reducing suture in the repair of hypertrophic scars. METHODS: A retrospective analysis of clinical data was conducted on 82 patients with hypertrophic scars treated at the Department of Burns and Plastic Surgery of Nanjing Drum Tower Hospital from September 2021 to December 2022. Patients were operated with combination of heart-shaped tension-reducing suturing technique and looped, broad, and deep buried (LBD) suturing technique or conventional suture method. Outcomes of surgical treatment were assessed before and 6 months after surgery using the Patient and Observer Scar Assessment Scale (POSAS) and the Vancouver Scar Scale (VSS). RESULTS: Improvements were achieved on scar quality compared to that preoperatively, with a reduction in scar width (1.7 ± 0.6 cm vs. 0.7 ± 0.2 cm, P < 0.001). Assessment using the POSAS and VSS scales showed significant improvements in each single parameter and total score compared to preoperative values (P < 0.05). The Combination method group achieved better score in total score of VSS scale, in color, stiffness, thickness and overall opinion of PSAS scale, and in vascularity, thickness, pliability and overall opinion of OSAS scale. CONCLUSION: The amalgamation of the heart-shaped tension-reducing suturing technique and the LBD suturing technique has shown promising outcomes, garnering notably high levels of patient satisfaction in the context of hypertrophic scar repair. Patients have exhibited favorable postoperative recoveries, underscoring the clinical merit and the prospective broader applicability of this approach in the realm of hypertrophic scar management.

Resveratrol activates autophagy and protects from UVA-induced photoaging in human skin fibroblasts and the skin of male mice by regulating the AMPK pathway.

Skin photoaging is mostly caused by ultraviolet A (UVA), although active medications to effectively counteract UVA-induced photoaging have not yet been created. Resveratrol, a naturally occurring polyphenol found in the skin of grapes, has been shown to have various biological functions such as anti-inflammatory and antioxidant characteristics. However, the role of resveratrol in UVA-induced photoaging has not been clarified. We investigated the mechanism of action of resveratrol by UVA irradiation of human skin fibroblasts (HSF) and innovatively modified a mouse model of photoaging. The results demonstrated that resveratrol promoted AMP-activated protein kinase (AMPK) phosphorylation to activate autophagy, reduce reactive oxygen species (ROS) production, inhibit apoptosis, and restore normal cell cycle to alleviate UVA-induced photoaging. In addition, subcutaneous injection of resveratrol not only improved the symptoms of roughness, erythema, and increased wrinkles in the skin of UVA photodamaged mice, but also alleviated epidermal hyperkeratosis and hyperpigmentation, reduced inflammatory responses, and inhibited collagen fiber degradation. In conclusion, our studies proved that resveratrol can treat UVA-induced photoaging and elucidated the possible molecular mechanisms involved, providing a new therapeutic strategy for future anti-aging.

Successful reimplantation of extruded bone segment in lower limb open fractures: case report and literature review.

Objective: The aim of this study is to summarize and demonstrate the different sterilization methods and surgical techniques for open fractures with impacted bone segments in the lower limbs. Methods: A retrospective analysis was conducted on the clinical characteristics, treatment methods, and outcomes of a case involving a 10.5 cm extruded segment of the femur in a 9-year-old male with a right femoral comminuted fracture treated at our center. Additionally, a retrospective review and summary were conducted on all reported cases of open fractures with impacted bone segments in the lower limbs. Results: Our center treated a 9-year and 11-month-old male child who presented with a Gustilo type IIIB open fracture of the femur along with a large segment of the femur being ejected as a result of a car accident. The child was resuscitated to correct hypovolemic shock, underwent emergency wound debridement, and had Ilizarov external fixation of the femur. The ejected femur segment was sterilized using ethylene oxide and re-implanted four days after the injury. A literature review showed that out of the cases of open fractures with impacted bone segments in the lower limbs, there were 14 cases involving the femur and 5 cases involving the tibia. Among them, sterilization was performed using povidone-iodine in 6 cases, high-pressure steam sterilization in 3 cases, and other methods including gamma-ray irradiation and soaking in antibacterial solution were used in the remaining cases. In terms of surgical methods, 7 cases were fixed with locking plates, 3 cases were fixed with external fixation devices, 1 case was immobilized in a cast, 1 case was fixed with an intramedullary rod, and 4 cases involved a combination of external fixation and internal fixation. The average time for re-implantation was 7.6 days after the injury. There were no serious complications such as infection or non-union observed in any of the cases during follow-up. Conclusion: Ethylene oxide can be considered a reliable choice for the reimplantation of displaced bone segments in open fractures after sterilization.

Land-use simulation for synergistic pollution and carbon reduction: Scenario analysis and policy implications.

Simulations of sustainable land use and management are required to achieve targets to reduce pollution and carbon emissions. Limited research has been conducted on synergistic pollution and carbon reduction (SPCR) in land-use simulations. This study proposed a framework for land-use simulation focused on SPCR. The non-dominated sorting genetic algorithm (NSGA-Ⅱ) and the entropy weight-based technique for order of preference by similarity to an ideal solution (TOPSIS) were used to optimize the land-use structure according to minimum net carbon, nitrogen, and phosphorus emissions. The cellular automata (CA) Markov model was then utilized to simulate the land-use spatial pattern according to the optimal conditions. The proposed framework was applied to the Dongjiang River Basin, South China, and three other scenarios (natural development (ND), carbon minimization (CM), and pollution minimization (PM)) were designed to validate the effectiveness of pollution and carbon emissions reduction under the SPCR scenario. The land-use structure and the pollution and carbon emissions in the scenarios were compared. The results showed the following. (1) The proportions of cultivated land, woodland, grassland, water, and construction land In the SPCR scenario accounted for 14%, 72%, 4%, 3%, and 7% of the total area, respectively. The carbon, nitrogen, and phosphorus emissions were 42.4%, 6.6%, and 7.8% lower, respectively, in the SPCR scenario than in the ND scenario, demonstrating the advantages of simultaneous pollution and carbon reduction. (2) The kappa coefficient of the CA-Markov model was 0.8729, indicating high simulation accuracy. (3) The simulated land-use spatial patterns exhibited low spatial heterogeneity under the CM, PM, and SPCR scenarios. However, there were significant disparities between the ND and SPCR scenarios. The cultivated and construction land areas were significantly smaller in the SPCR scenario than in the ND scenario. In contrast, the woodland and grassland areas were larger, with most differences in the central and southwestern regions of the Dongjiang River Basin. The results of the current study can be used to formulate effective land use policies and strategies in the Dongjiang Basin and similar areas to achieve the Coupling coordination between pollution reduction and carbon reduction. Policy recommendations include increasing the proportion of woodland and grassland, implementing reasonable constraints on expanding cultivated and construction lands, and establishing farmland red lines to promote synergistic pollution and carbon reduction.

Systematic evaluation of machine learning-enhanced trifocal IOL power selection for axial myopia cataract patients.

PURPOSE: This study aimed to evaluate and optimize intraocular lens (IOL) power selection for cataract patients with high axial myopia receiving trifocal IOLs. DESIGN: A multi-center, retrospective observational case series was conducted. Patients having an axial length ≥26 mm and undergoing cataract surgery with trifocal IOL implanted were studied. METHODS: Preoperative biometric and postoperative outcome data from 139 eyes were collected to train and test various machine learning (ML) models (support vector machine, linear regression, and stacking regressor) using five-fold cross-validation. The models' performance was further validated externally using data from 48 eyes enrolled from other hospitals. Performance of seven IOL calculation formulas (BUII, Kane, EVO, K6, DGS, Holladay I, and SRK/T) were examined with and without ML models. RESULTS: The results of cross-validation revealed improvements across all IOL calculation formulas, especially for K6 and Holladay I. The model increased the percentage of eyes with a prediction error (PE) within ±0.50 D from 71.94% to 79.14% for K6, and from 35.25% to 51.80% for Holladay I. In external validation involving 48 patients from other centers, six out of seven formulas demonstrated a reduction in the mean absolute error (MAE). K6's PE within ±0.50 D improved from 62.50% to 77.08%, and Holladay I from 16.67% to 58.33%. CONCLUSIONS: In this study, we conducted a comprehensive evaluation of seven IOL power calculation formulas in high axial myopia cases and explored the effectiveness of the Stacking Regressor model in augmenting their accuracy. Of these formulas, K6 and Holladay I exhibited the most significant improvements, suggesting that integrating ML may have varying levels of effectiveness across different formulas but holds substantial promise in improving the predictability of IOL power calculations in patients with long eyes.

The Wnt Co-Receptor PTK7/Otk and Its Homolog Otk-2 in Neurogenesis and Patterning.

Wnt signaling is a highly conserved metazoan pathway that plays a crucial role in cell fate determination and morphogenesis during development. Wnt ligands can induce disparate cellular responses. The exact mechanism behind these different outcomes is not fully understood but may be due to interactions with different receptors on the cell membrane. PTK7/Otk is a transmembrane receptor that is implicated in various developmental and physiological processes including cell polarity, cell migration, and invasion. Here, we examine two roles of Otk-1 and Otk-2 in patterning and neurogenesis. We find that Otk-1 is a positive regulator of signaling and Otk-2 functions as its inhibitor. We propose that PTK7/Otk functions in signaling, cell migration, and polarity contributing to the diversity of cellular responses seen in Wnt-mediated processes.

Flooding regimes alleviate lead toxicity and enhance phytostabilization of salix: Evidence from physiological responses and iron-plaque formation.

Aggravated metal pollution in wetland and riparian zones has become a global environmental issue, necessitating the identification of sustainable remediation approaches. Salix exhibits great potential as a viable candidate for metal(loid) remediation. However, the underlying mechanisms for its effectiveness in different flooding regimes with Pb pollution have not been extensively studied. In this study, fast-growing Salix×jiangsuensis 'J172' was selected and planted in different Pb polluted soils (control, 400 and 800 mg ∙ kg-1) under non-flooded and flooded (CF: continuous flooding and IF: intermittent flooding) conditions for 60 days. This study aimed to explore the effects of flooding on Salix growth performance, physiological traits, and the relationship between Pb uptake/translocation and root Fe plaques. Salix×jiangsuensis 'J172' exhibited excellent tolerance and adaptation to Pb pollution with a tolerance index (TI) exceeding 0.6, even at the highest Pb levels. Moreover, the TIs under flooded conditions were higher than that under non-flooded conditions, suggesting that flooding could alleviate Pb toxicity under co-exposure to Pb and flooding. Leaf malondialdehyde (MDA) exhibited a dose-dependent response to Pb exposure; however, CF or IF mitigated the oxidative damage induced by Pb toxicity with decreased MDA content (2.2-11.9%). The superoxide dismutase and peroxidase activities were generally enhanced by flooding, but combined stress (flooding and Pb) significantly decreased catalase activity. Pb was predominantly accumulated in Salix roots, and flooding markedly increased root Pb accumulation by 19.2-173.0% compared to non-flooded condition. Additionally, a significant positive correlation was observed between the iron (Fe) content of the root plaque and root Pb accumulation, indicating that the formation of Fe plaque on the root surface could enhance the phytostabilization of Pb in Salix. The current findings highlight that fast-growing woody plants are suitable for phyto-management of metal-polluted wetlands and can potentially minimize the risk of metal mobility in soils.

The changes of neurogenesis in the hippocampal dentate gyrus of SAMP8 mice and the effects of acupuncture and moxibustion.

BACKGROUND: Influenced by the global aging population, the incidence of Alzheimer's disease (AD) has increased sharply. In addition to increasing ß-amyloid plaque deposition and tau tangle formation, neurogenesis dysfunction has recently been observed in AD. Therefore, promoting regeneration to improve neurogenesis and cognitive dysfunction can play an effective role in AD treatment. Acupuncture and moxibustion have been widely used in the clinical treatment of neurodegenerative diseases because of their outstanding advantages such as early, functional, and benign two-way adjustment. It is urgent to clarify the effectiveness, greenness, and safety of acupuncture and moxibustion in promoting neurogenesis in AD treatment. METHODS: Senescence-accelerated mouse prone 8 (SAMP8) mice at various ages were used as experimental models to simulate the pathology and behaviors of AD mice. Behavioral experiments, immunohistochemistry, Western blot, and immunofluorescence experiments were used for comparison between different groups. RESULTS: Acupuncture and moxibustion could increase the number of PCNA+ DCX+ cells, Nissl bodies, and mature neurons in the hippocampal Dentate gyrus (DG) of SAMP8 mice, restore the hippocampal neurogenesis, delay the AD-related pathological presentation, and improve the learning and memory abilities of SAMP8 mice. CONCLUSION: The pathological process underlying AD and cognitive impairment were changed positively by improving the dysfunction of neurogenesis. This indicates the promising role of acupuncture and moxibustion in the prevention and treatment of AD.

Coupling and decoupling of soil carbon and nutrients cycles at different salinity levels in a mangrove wetland: Insights from CUE and enzymatic stoichiometry.

Soil carbon (C), nitrogen (N), and phosphorus (P) cycling, in conjunction with microbial metabolism, varies significantly with salinity in coastal areas. However, microbial metabolism limitation on salinity levels has received limited attention. Based on soil microbial carbon use efficiency and enzymatic stoichiometry, microbial nutrient limitation characteristics of soil microbial communities in different salinity levels (4.45 mS·cm-1 - 17.25 mS·cm-1) in a subtropical mangrove wetland were investigated. Compared to low-salinity levels, the activity of soil C-acquiring enzyme activities, enzymatic C:N ratios and enzymatic C:P ratios decreased with medium salinity levels and high salinity levels. Soil microbial metabolism was primarily constrained by C and N at different salinity levels. Boosted regression tree analysis revealed that abiotic factors had the greatest influence on C and N limitation of microbial metabolism at different salinity levels. This study underscores the significance of salinity in microbial metabolic processes and enhances our understanding of how future salinity changes induced by rising sea levels will affect soil carbon and nutrient cycling in coastal wetlands.

Eutrophication-driven infochemical dimethylsulfide accelerates carbon transfer in freshwater food chain.

Dimethylsulfide (DMS) is a major organic sulfide in aquatic ecosystems and an infochemical that is considered as a key predictor of changes in energy and material fluxes and stocks. It is largely unknown how DMS changes and affects the food webs and material cycles in eutrophicated freshwater. In this study, field monitoring and literature surveys were conducted to analyze the effects of eutrophication on DMS concentrations. Daphnia-zebrafish microcosms were then used to investigate the effects of DMS concentrations on carbon transfer. The results demonstrated that the concentration of DMS was increased by eutrophication related indicators (chlorophyll and phosphorus). Eutrophication driven DMS altered carbon transfer in the freshwater food chain. Low concentrations (0.1-1 nM) of DMS promoted the predation of daphnia by zebrafish compared to the 0.01 nM DMS, which further stimulated the total carbon transfer from daphnia to zebrafish and altered the dissolved organic carbon (DOC) distribution in water. High concentrations (10-100 nM) of DMS did not alter zebrafish predation on daphnia and carbon transfer. DOC excreted by zebrafish altered carbon emission potential, and DMS in water showed a unimodal relationship with the carbon emission potential, peaking at 0.40 nM DMS. Keeping the DMS in water at 1.82 nM may maintain a lower carbon emission potential. These results improved the understanding of the effects of eutrophication on DMS, demonstrated the ecological role of DMS on freshwater fish and the carbon cycle, estimated the effects of DMS on the carbon emission potential of fish, and offered new insights into the management of eutrophication.

Understanding phosphorus fractions and influential factors on urban road deposited sediments.

Phosphorus (P) is a primary pollutant that builds-up on urban road surfaces. Understanding the fraction and load characteristics of P, as well as their relationship with urban factors, is helpful for assessing the ecological risk of urban receiving water bodies. This study presents the characteristics of build-up loads of P fractions in road-deposited sediments (RDS) in Guangzhou, China, analyzes their correlation with three urban factors (road, traffic, and land-use area), and then estimates the exceedance probability of P in stormwater runoff over the past 10 years. The results showed that detrital apatite phosphorus (De-P) performed the highest build-up load on urban road surfaces, followed by apatite phosphorus (Ca-P), iron-bound phosphorus (Fe-P), exchangeable phosphorus (Ex-P), aluminum-bound phosphorus (Al-P), organophosphorus (POP), dissolved inorganic phosphorus (DIP), occluded phosphorus (Oc-P), and dissolved organic phosphorus (DOP). Depression depth, road materials, and land-use fractions affected the P fractions. The P in the RDS may have originated from three distinct sources: road background, domestic waste, and untreated wastewater discharge. In the most recent 10 years, the event mean concentrations of total P in the RDS have had a 30 % probability of exceeding 0.4 mg L-1, which indicates a serious threat of P to receiving water bodies. The outcomes of this study are expected to provide valuable guidance for elucidating the principal categories of urban non-point source P pollution and enhancing the ecological health of urban water environments.

Identification of small-molecule binding sites of a ubiquitin-conjugating enzyme-UBE2T through fragment-based screening.

UBE2T is an attractive target for drug development due to its linkage with several types of cancers. However, the druggability of ubiquitin-conjugating E2 (UBE2T) is low because of the lack of a deep and hydrophobic pocket capable of forming strong binding interactions with drug-like small molecules. Here, we performed fragment screening using 19 F-nuclear magnetic resonance (NMR) and validated the hits with 1 H-15 N-heteronuclear single quantum coherence (HSQC) experiment and X-ray crystallographic studies. The cocrystal structures obtained revealed the binding modes of the hit fragments and allowed for the characterization of the fragment-binding sites. Further screening of structural analogues resulted in the identification of a compound series with inhibitory effect on UBE2T activity. Our current study has identified two new binding pockets in UBE2T, which will be useful for the development of small molecules to regulate the function of this protein. In addition, the compounds identified in this study can serve as chemical starting points for the development of UBE2T modulators.

Bioactive triterpenoid compounds of Poria cocos (Schw.) Wolf in the treatment of diabetic ulcers via regulating the PI3K-AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic ulcers represent a chronic condition characterized by prolonged hyperglycemia and delayed wound healing, accompanied by endocrine disorders, inflammatory responses, and microvascular damage in the epidermal tissue, demanding effective clinical treatment approaches. For thousands of years, ancient Chinese ethnopharmacological studies have documented the use of Poria cocos (Schw.) Wolf in treating diabetic ulcers. Recent research has substantiated the diverse pharmacological effects of Poria cocos (Schw.) Wolf, including its potential to alleviate hyperglycemia and exhibit anti-inflammatory, antioxidant, and immune regulatory properties, which could effectively mitigate diabetic ulcer symptoms. Furthermore, being a natural medicine, Poria cocos (Schw.) Wolf has demonstrated promising therapeutic effects and safety in the management of diabetic ulcers, holding significant clinical value. Despite its potential clinical efficacy and applications in diabetic ulcer treatment, the primary active components and underlying pharmacological mechanisms of Poria cocos (Schw.) Wolf remains unclear. Further investigations are imperative to establish a solid foundation for drug development in this domain. AIM OF THE STUDY AND MATERIALS AND METHODS: In this study, we aimed to identify the active compounds and potential targets of Poria cocos (Schw.) Wolf using UHPLC-Q-TOF-MS and TCMSP databases. Additionally, we attempt to identify targets related to diabetic ulcers. Following enrichment analysis, a network of protein-protein interactions was constructed to identify hub genes based on the common elements between the two datasets. To gain insights into the binding activities of the hub genes and active ingredients, molecular docking analysis was employed. Furthermore, to further validate the therapeutic effect of Poria cocos (Schw.) Wolf, we exerted in vitro experiments using human umbilical vein vascular endothelial cells and human myeloid leukemia monocytes (THP-1). The active ingredient of Poria cocos (Schw.) Wolf was applied in these experiments. Our investigations included various assays, such as CCK-8, scratch test, immunofluorescence, western blotting, RT-PCR, and flow cytometry, to explore the potential of Poria cocos (Schw.) Wolf triterpenoid extract (PTE) in treating diabetic ulcers. RESULTS: The findings here highlighted PTE as the primary active ingredient in Poria cocos (Schw.) Wolf. Utilizing network pharmacology, we identified 74 potential targets associated with diabetic ulcer treatment for Poria cocos (Schw.) Wolf, with five hub genes (JUN, MAPK1, STAT3, AKT1, and CTNNB1). Enrichment analysis revealed the involvement of multiple pathways in the therapeutic process, with the PI3K-AKT signaling pathway showing significant enrichment. Through molecular docking, we discovered that relevant targets within this pathway exhibited strong binding with the active components of Poria cocos (Schw.) Wolf. In vitro experiments unveiled that PTE (10 mg/L) facilitated the migration of human umbilical vein vascular endothelial cells (P < 0.05). PTE also increased the expression of CD31 and VEGF mRNA (P < 0.05) while activating the expressions of p-PI3K and p-AKT (P < 0.05). Moreover, PTE demonstrated its potential by reducing the expression of IL-1ß, IL-6, TNF-α, and NF-κB mRNA in THP-1 (P < 0.05) and fostering M2 macrophage polarization. These results signify the potential therapeutic effects of PTE in treating diabetic ulcers, with its beneficial actions mediated through the PI3K-AKT signaling pathway. CONCLUSIONS: PTE is the main active ingredient in Poria cocos (Schw.) Wolf that exerts therapeutic effects. Through PI3K-AKT signaling pathway activation and inflammatory response reduction, PTE promotes angiogenesis, thereby healing diabetic ulcers.

Enzymatic properties of ornithine decarboxylase from Clostridium aceticum DSM1496.

Clostridium aceticum DSM1496 is an acid-resistant strain in which ornithine decarboxylase (ODC) plays a crucial role in acid resistance. In this study, we expressed ODC derived from C. aceticum DSM1496 in Escherichia coli BL21 (DE3) and thoroughly examined its enzymatic properties. The enzyme has a molecular weight of 55.27 kDa and uses pyridoxal-5'-phosphate (PLP) as a coenzyme with a Km  = 0.31 mM. ODC exhibits optimal activity at pH 7.5, and it maintains high stability even at pH 4.5. The peak reaction temperature for ODC is 30°C. Besides, it can be influenced by certain metal ions such as Mn2+ . Although l-ornithine serves as the preferred substrate for ODC, the enzyme also decarboxylates l-arginine and l-lysine simultaneously. The results indicate that ODC derived from C. aceticum DSM1496 exhibits the ability to produce putrescine, cadaverine, and agmatine through decarboxylation. These polyamines have the potential to neutralize acid in an acidic environment, facilitating the growth of microorganisms. These significant findings provide a strong basis for further investigation into the acid-resistant mechanisms contributed by ODC.

The RING Domain of Rice HEI10 is Essential for Male, But Not Female Fertility.

HEI10 is a conserved E3 ubiquitin ligase involved in crossover formation during meiosis, and is thus essential for both male and female gamete development. Here, we have discovered a novel allele of HEI10 in rice that produces a truncated HEI10 protein missing its N-terminal RING domain, namely sh1 (shorter hei10 1). Unlike previously reported hei10 null alleles that are completely sterile, sh1 exhibits complete male sterility but retains partial female fertility. The causative sh1 mutation is a 76 kb inversion between OsFYVE4 and HEI10, which breaks the integrity of both genes. Allelic tests and complementation assays revealed that the gamete developmental defects of sh1 were caused by disruption of HEI10. Further studies demonstrated that short HEI10 can correctly localise to the nucleus, where it could interact with other proteins that direct meiosis; expressing short HEI10 in hei10 null lines partially restores female fertility. Our data reveal an intriguing mutant allele of HEI10 with differential effects on male and female fertility, providing a new tool to explore similarities and differences between male and female meiosis.

Barriers and facilitators experienced in delivering alcohol screening and brief interventions in community pharmacy: a qualitative evidence synthesis.

BACKGROUND: Following increases in deaths due to alcohol during the COVID-19 pandemic, there have been renewed calls to increase resources in alcohol screening and brief intervention (SBI). Research has shown that community pharmacy could be a promising setting for SBI. This review aimed to investigate the barriers and facilitators to SBI delivery in community pharmacy to inform its further development. METHODS: A systematic search of four databases (MEDLINE, EMBASE, CINAHL, and PsycINFO) was conducted in October 2021 to identify relevant published qualitative or mixed-method studies. Relevant qualitative data were extracted from the included studies and a framework synthesis was performed using the Capability-Opportunity-Motivation-Behaviour (COM-B) model. RESULTS: Two thousand two hundred and ten articles were screened and nine studies were included in the review (seven in the United Kingdom and two in Australia). Identified barriers and facilitators to delivering SBI corresponded to all components of the COM-B model. Facilitators included non-confrontational communication skills, aligning SBI with existing pharmacy services and pharmacist role legitimacy. Barriers included multiple demands on staff time, a lack of staff experience with screening tools, and staff concerns of causing offence. Using the Behaviour Change Wheel (BCW), we propose five elements of a pharmacy SBI to address identified barriers. CONCLUSIONS: Research into SBI in community pharmacy is limited in comparison to other healthcare settings and this review provides an understanding of the barriers and facilitators to the delivery of SBI in community pharmacy from a behavioural perspective. Through the use of COM-B and BCW, our findings could inform the development of future pharmacy-based SBI.