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BackgroundDespite growing interest in the clinical translation of polygenic risk scores (PRSs), it remains uncertain to what extent genomic information can enhance the prediction of psychiatric outcomes beyond the data collected during clinical visits alone. ObjectiveThis study aimed to assess the clinical utility of incorporating PRSs into a suicide risk prediction model trained on electronic health records (EHRs) and patient-reported surveys among patients admitted to the emergency department. MethodsStudy participants were recruited from the psychiatric emergency department at Massachusetts General Hospital. There were 333 adult patients of European ancestry who had high-quality genotype data available through their participation in the Mass General Brigham Biobank. Multiple neuropsychiatric PRSs were added to a previously validated suicide prediction model in a prospective cohort enrolled between February 4, 2015, and March 13, 2017. Data analysis was performed from July 11, 2022, to August 31, 2023. Suicide attempt was defined using diagnostic codes from longitudinal EHRs combined with 6-month follow-up surveys. The clinical risk score for suicide attempt was calculated from an ensemble model trained using an EHR-based suicide risk score and a brief survey, and it was subsequently used to define the baseline model. We generated PRSs for depression, bipolar disorder, schizophrenia, suicide attempt, and externalizing traits using a Bayesian polygenic scoring method for European ancestry participants. Model performance was evaluated using area under the receiver operator curve (AUC), area under the precision-recall curve, and positive predictive values. ResultsOf the 333 patients (n=178, 53.5% male; mean age 36.8, SD 13.6 years; n=333, 100% non-Hispanic and n=324, 97.3% self-reported White), 28 (8.4%) had a suicide attempt within 6 months. Adding either the schizophrenia PRS or all PRSs to the baseline model resulted in the numerically highest discrimination (AUC 0.86, 95% CI 0.73-0.99) compared to the baseline model (AUC 0.84, 95% Cl 0.70-0.98). However, the improvement in model performance was not statistically significant. ConclusionsIn this study, incorporating genomic information into clinical prediction models for suicide attempt did not improve patient risk stratification. Larger studies that include more diverse participants are required to validate whether the inclusion of psychiatric PRSs in clinical prediction models can enhance the stratification of patients at risk of suicide attempts.

PurposeParotid gland metastases originating from breast origin are extremely rare, with their clinical presentation, therapeutic approaches, and prognostic indicators remaining to be elucidate.MethodsA comprehensive retrospective review was conducted, analyzing the clinical characteristics and prognostic factors of 57 patients diagnosed with parotid metastasis of breast cancer in the existing literature. Notably, our study included two unique cases of patients who developed contralateral and ipsilateral parotid metastases, occurring 5 years and 32 years respectively after primary surgery. This analysis aimed to provide a deeper understanding of the disease presentation and identify potential prognostic indicators.ResultsThe primary clinical manifestation presented in breast cancer patients with parotid metastases was painless masses in the parotid glands, synchronously or metachronously occurred with primary breast tumors. The predominant pathological subtype among these patients was invasive ductal carcinoma. Out of the 57 patients studied, 24 (42.1%) exhibited metastases solely in the ipsilateral parotid gland, while 18 cases (31.6%) involved either the contralateral or bilateral parotid gland. Patients may solely exhibit metastasis in the parotid gland, or they may present with concurrent multiple metastases in other organs. Patients who suffered from parotid metastases, either merely or accompanied with bone-only metastasis, exhibited significantly longer overall survival (OS) rates compared to those who had concomitant metastases in other organs (1.23 ± 0.26 years vs 4.46 ± 0.77 years, P=0.046). While no statistically significant differences in OS were observed among patients presenting with metastases in the ipsilateral, contralateral, or bilateral parotid glands, a notable variance could be discerned from the Kaplan-Meier curve analysis. Additionally, no significant difference in survival was exhibited between patients with different interval of progression from primary breast sites to initial diagnosis of parotid metastases (uDF), nor for patients who were treated with surgery or palliative therapy.ConclusionParotid metastasis, a rare and distinctive form of breast cancer metastasis, demands particular scrutiny in patients exhibiting metastasis to multiple organs or contralateral or bilateral parotid glands.

Abstract Utilization of digital technologies for cataract screening in primary care is a potential solution for addressing the dilemma between the growing aging population and unequally distributed resources. Here, we propose a digital technology-driven hierarchical screening (DH screening) pattern implemented in China to promote the equity and accessibility of healthcare. It consists of home-based mobile artificial intelligence (AI) screening, community-based AI diagnosis, and referral to hospitals. We utilize decision-analytic Markov models to evaluate the cost-effectiveness and cost-utility of different cataract screening strategies (no screening, telescreening, AI screening and DH screening). A simulated cohort of 100,000 individuals from age 50 is built through a total of 30 1-year Markov cycles. The primary outcomes are incremental cost-effectiveness ratio and incremental cost-utility ratio. The results show that DH screening dominates no screening, telescreening and AI screening in urban and rural China. Annual DH screening emerges as the most economically effective strategy with 341 (338 to 344) and 1326 (1312 to 1340) years of blindness avoided compared with telescreening, and 37 (35 to 39) and 140 (131 to 148) years compared with AI screening in urban and rural settings, respectively. The findings remain robust across all sensitivity analyses conducted. Here, we report that DH screening is cost-effective in urban and rural China, and the annual screening proves to be the most cost-effective option, providing an economic rationale for policymakers promoting public eye health in low- and middle-income countries.

Goals: We have recently introduced a new class of wearable loop sensors for joint flexion monitoring that overcomes limitations in the state-of-the-art. Our previous studies reported a proof-of-concept on a cylindrical phantom limb, under static scenarios and with a rigid sensor. In this work, we evaluate our sensors, for the first time, on human subjects, under dynamic scenarios, using a flexible textile-based prototype tethered to a network analyzer. An untethered version is also presented and validated on phantoms, aiming towards a fully wearable design. Methods: Three dynamic activities (walking, brisk walking, and full flexion/extension, all performed in place) are used to validate the tethered sensor on ten (10) adults. The untethered sensor is validated upon a cylindrical phantom that is bent manually at random speed. A calibration mechanism is developed to derive the sensor-measured angles. These angles are then compared to gold-standard angles simultaneously captured by a light detection and ranging (LiDAR) depth camera using root mean square error (RMSE) and Pearson's correlation coefficient as metrics. Results: We find excellent correlation (≥ 0.981) to gold-standard angles. The sensor achieves an RMSE of 4.463° ± 1.266° for walking, 5.541° ± 2.082° for brisk walking, 3.657° ± 1.815° for full flexion/extension activities, and 0.670° ± 0.366° for the phantom bending test. Conclusion: The tethered sensor achieves similar to slightly higher RMSE as compared to other wearable flexion sensors on human subjects, while the untethered version achieves excellent RMSE on the phantom model. Concurrently, our sensors are reliable over time and injury-safe, and do not obstruct natural movement. Our results set the ground for future improvements in angular resolution and for realizing fully wearable designs, while maintaining the abovementioned advantages over the state-of-the-art.

Abstract Background Ongoing symptoms or the development of new symptoms following a SARS-CoV-2 diagnosis has caused a complex clinical problem known as “long COVID” (LC). This has introduced further pressure on global healthcare systems as there appears to be a need for ongoing clinical management of these patients. LC personifies heterogeneous symptoms at varying frequencies. The most complex symptoms appear to be driven by the neurology and neuropsychiatry spheres. Methods A systematic protocol was developed, peer reviewed, and published in PROSPERO. The systematic review included publications from the 1st of December 2019–30th June 2021 published in English. Multiple electronic databases were used. The dataset has been analyzed using a random-effects model and a subgroup analysis based on geographical location. Prevalence and 95% confidence intervals (CIs) were established based on the data identified. Results Of the 302 studies, 49 met the inclusion criteria, although 36 studies were included in the meta-analysis. The 36 studies had a collective sample size of 11,598 LC patients. 18 of the 36 studies were designed as cohorts and the remainder were cross-sectional. Symptoms of mental health, gastrointestinal, cardiopulmonary, neurological, and pain were reported. Conclusions The quality that differentiates this meta-analysis is that they are cohort and cross-sectional studies with follow-up. It is evident that there is limited knowledge available of LC and current clinical management strategies may be suboptimal as a result. Clinical practice improvements will require more comprehensive clinical research, enabling effective evidence-based approaches to better support patients.

We have previously reported wearable loop sensors that can accurately monitor knee flexion with unique merits over the state of the art. However, validation to date has been limited to single-leg configurations, discrete flexion angles, and in vitro (phantom-based) experiments. In this work, we take a major step forward to explore the bilateral monitoring of knee flexion angles, in a continuous manner, in vivo. The manuscript provides the theoretical framework of bilateral sensor operation and reports a detailed error analysis that has not been previously reported for wearable loop sensors. This includes the flatness of calibration curves that limits resolution at small angles (such as during walking) as well as the presence of motional electromotive force (EMF) noise at high angular velocities (such as during running). A novel fabrication method for flexible and mechanically robust loops is also introduced. Electromagnetic simulations and phantom-based experimental studies optimize the setup and evaluate feasibility. Proof-of-concept in vivo validation is then conducted for a human subject performing three activities (walking, brisk walking, and running), each lasting 30 s and repeated three times. The results demonstrate a promising root mean square error (RMSE) of less than 3° in most cases.

Lung cancer is one of the leading causes of cancer-related death. Lung cancer mortality has decreased over the past decade, which is partly attributed to improved treatments. Curative surgery for patients with early-stage lung cancer is the standard of care, but not all surgical treatments have a good prognosis. Adjuvant and neoadjuvant chemotherapy are used to improve the prognosis of patients with resectable lung cancer. Immunotherapy, an epoch-defining treatment, has improved curative effects, prognosis, and tolerability compared with traditional and ordinary cytotoxic chemotherapy, providing new hope for patients with non-small cell lung cancer (NSCLC). Immunotherapy-related clinical trials have reported encouraging clinical outcomes in their exploration of different types of perioperative immunotherapy, from neoadjuvant immune checkpoint inhibitor (ICI) monotherapy, neoadjuvant immune-combination therapy (chemoimmunotherapy, immunotherapy plus antiangiogenic therapy, immunotherapy plus radiotherapy, or concurrent chemoradiotherapy), adjuvant immunotherapy, and neoadjuvant combined adjuvant immunotherapy. Phase 3 studies such as IMpower 010 and CheckMate 816 reported survival benefits of perioperative immunotherapy for operable patients. This review summarizes up-to-date clinical studies and analyzes the efficiency and feasibility of different neoadjuvant therapies and biomarkers to identify optimal types of perioperative immunotherapy for NSCLC.

Abstract Background Childhood internalizing and externalizing problems frequently co‐occur. Many studies report neural correlates of either internalizing or externalizing problems, but few account for their co‐occurrence. We aimed to assess specific cortical substrates of these psychiatric problems. Methods We used data from 9635 children aged 9–11 years in the baseline Adolescent Brain Cognitive Development Study. Internalizing and externalizing problem composite scales scores were derived from the Child Behavior Checklist. We standardized FreeSurfer‐derived volumes of 68 cortical regions. We examined internalizing and externalizing problems separately and jointly (covariate‐adjustment) in relation to cortical volumes, with and without adjusting for total brain volume (TBV) in multivariate linear regressions adjusted for demographics and multiple comparisons. We fit bifactor models to confirm the consistency of patterns exploring specific internalizing and specific externalizing problems. Sensitivity analyses included a vertex‐wide analysis and a replication in another large population‐based study. Results In separate TBV‐unadjusted analyses, externalizing and internalizing problems were associated with smaller cortical volumes. If adjusted for externalizing behavior, however, larger cortical volumes were associated with internalizing problems, while smaller cortical volumes remained associated with externalizing problems after adjustment for internalizing problems. The bifactor model produced similar results, which were consistently replicated in another pre‐adolescent neuroimaging sample. These associations likely represent global effects: adjusting for TBV rendered most associations non‐significant. Vertex‐wise analyses confirmed global patterns. Conclusion Our results suggest that internalizing and externalizing problems have globally opposing, and non‐specific associations with cortical morphology in childhood, which are only apparent if analyses account for their co‐occurrence.

Abstract Background Glasgow, Scotland, has previously shown exceptional levels of violence among young men, shows aggregations of health conditions, with shortened life expectancy. Health conditions can be both causes and consequences of violence, of shared community-level socio-economic risk factors, and can result from large-scale social forces beyond the control of populations with high levels of violence. The aim of the study was to provide an in depth understanding of the Public Health problem of violence among young adult men in Glasgow East. Method Ecological investigation of violence and its associations with health conditions in areas of contrasting socioeconomic deprivation. National survey of 1916 British men aged 18–34 years, augmented by a sub-sample of 765 men in Glasgow East (GE). Participants completed questionnaires covering current physical and sexual health, psychiatric symptoms, substance misuse, lifestyle, and crime and violence. Results The 5-year prevalence of violence was similar in both surveys but fights involving weapons (AOR 3.32, 95% CI 2.29–4.79), gang fights (AOR 2.30, 95% CI 1.77–2.98), and instrumental violence supporting criminal lifestyles were more common in GE, where 1 in 9 men had been in prison. Violent men in both samples reported poorer physical and sexual health and all types of psychiatric morbidity except depression, with multiple high-risk behaviours for both future poor health and violence. Associations between drug and alcohol dependence and violence in GE could not be entirely explained by deprivation. Conclusion Violence in deprived urban areas is one among many high-risk behaviours and lifestyle factors leading to, as well as resulting from, aggregations of both psychiatric and physical health conditions. Poverty partly explained raised levels of violence in GE. Other factors such as drug and alcohol misuse and macho attitudes to violence, highly prevalent among men in this socially excluded community, also contributed. Multi-component preventive interventions may be needed in deprived areas and require future investigations into how multiple co-existing risk factors produce multimorbidity, including psychiatric disorders, substance misuse, poor physical health and violence.

Introduction Primary angle-closure glaucoma (PACG) is a major subtype of glaucoma that accounts for most bilateral glaucoma-related blindness globally. Filtering surgery is a conventional strategy for PACG, yet it has a long learning curve and undesirable disastrous complications. Minimally invasive glaucoma surgery (MIGS) plays an increasing role in the management of glaucoma due to its safer and faster recovery profile; cataract surgery-based MIGS is the most commonly performed such procedure in PACG. However, for patients with a transparent lens or no indications for cataract extraction, incorporation of MIGS into PACG treatment has not yet been reported. Therefore, this multicentre, non-inferiority, randomised controlled clinical trial aims to compare the efficacy and safety of trabeculectomy versus peripheral iridectomy plus an ab interno goniotomy in advanced PACG with no or mild cataracts.Methods and analysis This non-inferiority, multicentre, randomised controlled trial will be conducted at seven ophthalmic departments and institutes across China. Eighty-eight patients with no or mild cataracts and advanced PACG will be enrolled and randomised to undergo trabeculectomy or peripheral iridectomy plus ab interno goniotomy. Enrolled patients will undergo comprehensive ophthalmic examinations before and after surgery. The primary outcome is intraocular pressure (IOP) at 12 months postoperatively. The secondary outcomes are cumulative success rate of surgery, surgery-related complications and number of IOP-lowering medications. Participants will be followed up for 36 months postoperatively.Ethics and dissemination The study protocol was approved by the ethical committees of the Zhongshan Ophthalmic Center, Sun Yat-sen University, China (ID: 2021KYPJ191) and of all subcentres. All participants will be required to provide written informed consent. The results will be published in peer-reviewed journals and disseminated in international academic meetings.Trial registration number NCT05163951.

Patients with hypertrophic cardiomyopathy (HCM), which is characterized by left ventricular hypertrophy, is usually treated with medications such as calcium channel blockers or beta-blockers and invasive treatments such as transcatheter alcohol septal ablation, percutaneous radiofrequency ablation, or heart transplantation. However, non-invasive methods have not been employed for the management of patients with HCM. A 71-year-old male who presented with occasional chest pain for approximately 2 months and had been diagnosed with HCM since he was 39 years old due to occasional fainting was treated with a novel method for HCM using stereotactic body radiotherapy (SBRT). The administration of 25 Gy of radiation as one fraction led to an improvement in his quality of life. No toxicity occurred during or immediately after the treatment. Our observations suggest that SBRT may be a reasonable treatment approach for patients with HCM who are not suitable for surgery.

Abstract Background Residential mobility during childhood increases risk of psychopathology in adulthood and is a common experience among Chinese children. This study investigated associations between number and age of first move, etiological risk factors for psychopathology, and common mental disorders in adolescence and early adulthood. Methods The sample included 39,531 undergraduates (84.5% completion rate) age 15–34 years in their first year at a Chinese comprehensive university in annual cross-sectional surveys during 2014–2018. Common mental disorders measured using standardised self-report instruments. Data analysed using logistic regression models and interaction analysis. Results Half of all students experienced one or more moves of residence before age 15 years. Outcomes of Depression, Somatisation, Obsessive-compulsive disorder, Hallucinations and Delusions, and Suicide attempts showed dose-response relationships with increasing number of moves. Other etiological risk factors, including childhood disadvantage and maltreatment, showed similar dose response relationships but did not confound associations with mobility. We found interactions between reporting any move and being a left-behind child on depression and somatisation; number of moves and younger age at first move on depression, somatisation, suicide attempts and hallucinations and delusions. Conclusions Residential mobility in childhood is associated with psychopathology in adulthood and this association increases with increasing number of moves. Mobility is also associated with childhood disadvantage and maltreatment but associations with psychopathology are independent of these factors. Multiplicative effects were shown for multiple moves starting at a younger age and if the participant had been a left-behind child.

PurposeUniversity students experience high levels of stress, and the prevalence of depression is higher than in the general population. The reason is not clear. More effective interventions and better prevention are needed.MethodsWe did annual cross-sectional surveys of Chinese undergraduates 2014–2018 (mean age 18.7 [SD 2.1], N = 39,573). We measured adaptation to university life using the Adolescent Self-rating Life Events Checklist (ASLEC) and common mental disorders using standardized self-report instruments. Regression analyses identified associations between childhood maltreatment, current family problems, stress in adaptation to undergraduate life, and psychiatric morbidity. Mediation analyses further tested relationships between these factors.ResultsChildhood maltreatment, current family problems, stress in adaptation, and psychiatric morbidity were all significantly associated with each other. The strongest association between childhood experiences and psychiatric morbidity was for sexual abuse and depression (OR = 3.39, 95%CI: 2.38–4.83, p < 0.001) and between stress from adaptation and somatic disorder (OR = 4.54, 95%CI: 3.62–5.68, p < 0.001). Associations between childhood maltreatment and stress from university life were partly mediated by psychiatric morbidity. Associations between family problems and psychiatric morbidity were mediated by stress from university life.ConclusionsStress from adaptation to university life and pressures from academic study exert stronger effects on psychiatric morbidity among students than childhood traumatic experiences and current family problems, although these factors are closely interrelated. Mental health services for students should focus on adaptation to university life and pressures from academic study as well as external factors of childhood trauma and family problems.

The flap side-edge is a vital contributor to airframe noise. In this study, we propose a novel flap side-edge noise reduction method based on the concept of active blowing air. A long slot is opened from the flap’s lower surface to the tip surface to induce a secondary jet flow, which is driven by the local pressure difference between the flap’s lower surface and the tip surface. The unsteady flow field around the flap side-edge was computed by the lattice Boltzmann solver PowerFLOW, and the far-field noise was predicted by the FW-H equation. It is demonstrated that the dominant features of the flap side-edge flow are the double vortex structures, and the new passive blowing air reduction method can achieve about 3.3 dB noise reduction. Moreover, the underlying noise reduction mechanism has been analyzed and revealed. It is shown that the secondary jet flow from the long slot on the flap side-edge would dissipate the flap side-edge vortex and displace the flap side-edge vortical structure away from the flap surface, thus resulting in a decrease in the pressure fluctuations on the flap side-edge surface. As a result, the flap side-edge noise was reduced. In contrast to the current active air blowing technique, the newly proposed blowing air technique is passive and quite simple and does not require an extra air source or control system. This novel flap side-edge noise reduction technology provides a new flow control strategy and noise reduction methodology and can be further optimized.

Introduction Primary angle-closure glaucoma (PACG) has a high prevalence and blinding rate across Asia. The first-line treatment of PACG is surgery, and phacotrabeculectomy remains the mainstream surgery for advanced PACG. However, it may cause vision-threatening complications with long learning curve. Minimally invasive glaucoma surgery has been gradually used in PACG combined with cataract surgery and achieved efficacy without excessive injury, of which goniotomy is the most commonly performed. Therefore, this study aimed to conduct a multicentre, non-inferiority randomised controlled clinical trial to compare the efficacy and safety of phacotrabeculectomy versus phacogoniotomy in advanced PACG.Methods and analysis This is a non-inferiority multicentre randomised controlled trial and will be conducted at eight ophthalmic departments and institutes in China. 124 patients with advanced PACG will be enrolled and randomised to undergo phacotrabeculectomy or phacogoniotomy. Comprehensive ophthalmic examinations will be performed before and after the surgery. The primary outcome is the change of intraocular pressure at 12 months after surgery compared with the baseline intraocular pressure. An extended follow-up period of 36 months will be required. Cumulative success rate of surgery, intraoperative and postoperative complications, and number of anti-glaucomatous medications will also be compared between the groups as secondary outcomes.Ethics and dissemination Ethical approval has been obtained from the ethical committee of Zhongshan Ophthalmic Center, Sun Yat-sen University, China (ID: 2021KYPJ090) and all subcentres. All the participants will be required to provide written informed consent. The results will be disseminated through scientific meetings and published in peer-reviewed journals.Trial registration number NCT04878458.

Background: Scotland has the shortest life expectancy in Western Europe, driven by high rates of cancer, suicides, alcohol-related causes and drug-related poisonings. These disparities cannot be explained solely by socioeconomic deprivation. Our aim was to investigate whether a syndemic in a socioeconomically deprived area of Glasgow might account for premature mortality among men. Methods: We analysed data from two cross-sectional population surveys: a national sample of 1916 British men and another of 765 men in Glasgow East. The survey included men aged 18–34, and was undertaken in 2011 to study correlates of violence. Questionnaires covered current physical health, psychiatric symptoms, substance misuse, and crime and violence. Syndemic components were identified using confirmatory factor analysis. Associations and synergistic interactions between these variables and health status were estimated using logistic regression. Results: An aggregation of multiple health conditions and health-related behaviours was found in Glasgow East. A syndemic model of joint effects, adducing a four-component latent variable (violence, substance dependence, psychiatric morbidity and a diathesis of biological/behavioural risk) showed synergy between components and explained persistent disparities in poor physical health/chronic health conditions. Effect modification was found between the general syndemic factor and contextual variables at individual and social environmental level according to location. Conclusions: Syndemic effects from synergistic interactions were confirmed between psychiatric morbidity, substance misuse, violence, and biological/behavioural risk for physical health. A hypothetical model was developed to explain how the syndemic leads to potentially life-threatening risks to young men, both currently and as precursors of physical health conditions which may shorten their lives in the future.

This study investigates Al-Mg2Si-Si alloy joints produced via resistance spot welding (RSW) with and without the use of Al-Si interlayers. The joint microstructures produced both with and without Al-Si interlayers consist of three zones: the base material (BM), the heat affected zone (HAZ) and the weld nugget (WN). The WN is oval, and increases in the welding current increase the WN size in both welding methods. The joints produced via RSW with an Al-Si interlayer have larger WNs than those produced without an interlayer under the same welding current conditions. Relationships between the welding current and the WN size are established by Gaussian fitting and Lorentz fitting. A comparison of the two welding approaches shows that a successful weld can be obtained at a low welding current when an Al-Si interlayer is used, whereas a larger welding current is required to obtain the same result without the use of an Al-Si interlayer. The transition layer (interface between the HAZ and the WN) in the joints welded without an interlayer is a single eutectic phase structure; however, in the joints welded with an interlayer, the transition layer generates an equiaxed-columnar crystal zone. The formation of the equiaxed-columnar crystal zone and the change in composition of the WN (according to the results of differential scanning calorimetry tests) improve the tensile-shear loads (TSLs). The equations of the peak TSLs as a function of the welding current and WN size are established by Gaussian fitting. Keywords: Al-Mg2Si-Si alloy, Resistance spot welding, Interlayer, Microstructure, Mechanical properties

Abstract Psoralen could inhibit the proliferation of human breast cancer cells, however, the molecular mechanism was unclear. We evaluated the anti-proliferative effects of psoralen by MTT, plate colony formation assay and cell cycle analysis in MCF-7 and MDA-MB-231 cells. The effects of psoralen on activation of Wnt/β-catenin and the related target genes were examined by quantitative real-time PCR, western blotting and cell immunofluorescence. The tumor growth was conducted in BALB/c nude mice and the pathological changes of heart, liver and kidney were also observed. Our results demonstrate that psoralen significantly inhibited cell proliferation by inducing G0/G1 phase arrest in MCF-7 cells and G2/M phase arrest in MDA-MB-231 cells. The expression of Fra-1 was reduced and Axin2 was promoted both in MCF-7 and MDA-MB-231 cells after psoralen treatment. The cytoplasmic accumulation and nuclear translocation of β-catenin were significantly reduced by psoralen. Psoralen increased the levels of phospho-(Y142) β-catenin, while decreased the expression of total β-catenin and its downstream target Fra-1 in vitro and vivo. Moreover, psoralen didn’t cause any significant toxicity at the effective concentration. Overall, our results might provide theoretical basis for clinical application of psoralen in breast cancer.

Trps1 is considered as an important gene involved in the interactions between the epithelial and mesenchymal cells during hair follicle morphogenesis. The number of hair follicles in Trps1 Knockout (KO) newborn mouse skin was significantly lower than that in wild-type (WT) newborn skin. To gain insight into the functional role of Trps1 in hair development, we transplanted Trps1 KO newborn mouse skin on the backs of nude mice and examined hair growth at day 42 after transplantation. Surprisingly, transplanted skin from Trps1 KO newborn mice gave rise to substantial amount of hair, although the hair was softer than that of WT mice. Histological examination revealed that the diameter of both hair follicles and hair shafts were significantly lower, whereas the density of hair follicles showed no significant difference between the Trps1 KO and WT mice. We introduce mouse hair follicles as a fascinating model to study the functions of Trps1 in mouse hair growth and pathology. This model suggests that the function of Trps1 is unnecessary for the development of normal hair follicles and hair shafts, although the loss of Trps1 affects the diameters of hair follicles and hair shaft.

Background. Plasma cell mastitis (PCM) is one of the most frequently encountered inflammatory diseases of the nonlactating breast. However, its pathogenesis has remained unknown. Methods. In this study, we observed the ultrastructure changes of PCM by a transmission electron microscope. The transcriptome expression difference of exosomes was detected by RNA-Seq; then, we confirmed the key difference genes by western blot and immunohistochemistry. Finally, we established the mouse PCM model by tissue homogenate injection to validate the role of exosomes on the progression of PCM. Results. The analysis of the exosomal transcriptome expression difference between PCM and normal mammary tissues using RNA-Seq showed the differential genes and enrichment pathways involved in the course of PCM. The decreased HSP90AA1 and EEF2, excessive production of p-AKT, and p-mTOR were consistent with clinical specimens. Inhibition of exosome secretion significantly inhibited inflammatory cell infiltration, and the mammary duct had maintained a better structure in the PCM mouse model. Conclusion. Our results revealed the role of exosomes acting as critical signal introduction facilitators in the progression of plasma cell mastitis and identified potential key genes in the regulation of this process. These results will help to dissect the molecular mechanism of PCM and provide therapeutic targets.

High-power fiber laser welding is an efficient and effective way to produce heavy section structures. However, there is a significant challenge in producing the welds with free of imperfections such as nail-head-shaped welds, spatters, and root sagging. This is partially due to a lack of understanding of the welding mechanism of high-power fiber laser. In this paper, we were especially interested in the mechanism to improve the appearance of welds, and we focused on the autogenous laser welding on thick stainless steel plates by a 10 kW fiber laser. To look into the relations of process parameters and the quality of welds, a high-speed imaging system was applied to observe the molten pool flow and vapor plume during the welding process. The appearances of welds subjected to different welding conditions were analyzed. The results showed that (1) nail-head-shaped welds were suppressed by using a gas jet during laser welding process. (2) In the forward welding, a gentle upwelling molten metal flow on the rear keyhole wall, a deeper weld pool and a weaker vapor plume resulted in no spatter. (3) The gravity affected the formation of underfills and root sagging significantly during autogenous laser welding of thick plates. (4) When the workpiece was placed vertically in the transverse position, the welding process was stable without an aggregation of molten melt at the back surface. Moreover, the mechanisms of forming root sagging and humps were different at the top surface.