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Vitiligo is an autoimmune disease characterized by the loss of functional melanocytes in the hair follicles and epidermis, leading to white patches on the skin and mucous membranes. Alopecia areata (AA) is a common immune-mediated condition in which autoimmune attack on hair follicles cause non-scarring hair loss. Both diseases significantly impact patients’s physical and mental health. Hair follicles, dynamic mini-organs, house diverse stem cell populations that form hair structures. Melanocyte stem cell (McSCs) and hair follicle stem cells (HFSC) located in the hair follicle bulge contribute to follicular structures during each anagen phase of the hair cycle, synchronizing periodic activities to impact color to the hair. Hair follicle dysfunction may contribute to hair loss and could potentially interfere with repigmentation efforts in vitiligo lesions. This article reviews the role of hair follicles in the pathogenesis, clinical manifestations, and therapeutic options for vitiligo and AA, aiming to deepen clinicians’ understanding of follicular involvement in these diseases and explore potential treatment avenues.

Conservation tillage (CT) is an important agronomic measure that facilitates soil organic carbon (SOC) accumulation by reducing soil disturbance and plant residue mulching, thus increasing crop yields, improving soil fertility and achieving C neutrality. However, our understanding of the microbial mechanism underlying SOC fraction accumulation under different tillage practices is still lacking. Here, a 6-year in situ field experiment was carried out to explore the effects of CT and traditional tillage (CK) practices on SOC fractions in an eolian sandy soil. Compared with CK, CT increased the particulate OC (POC) content in the 0–30 cm soil layer and the mineral-associated OC (MAOC) content in the 0–20 cm soil layer. Moreover, tillage type and soil depth had significant influences on the bacterial, fungal and protistan community compositions and structures. The co-occurrence network was divided into 4 ecological modules, and module 1 exhibited significant correlations with the POC and MOC contents. After determining their topological roles, we identified the keystone taxa in the network. The results indicated that the most common bacterial taxa may result in SOC loss due to low C use efficiency, while specific fungal (Cephalotrichum) and protistan (Cercozoa) species could facilitate SOC fraction accumulation by promoting macroaggregate formation and predation. Therefore, the increase in keystone fungi and protists, as well as the reduction in bacteria, drove module 1 community function, which in turn promoted SOC sequestration under CT. These results strengthen our understanding of microbial functions in the accrual of SOC fractions, which contributes to the development of conservation agriculture on the Northeast China Plain.

In response to the low recall rate of detection-based methods and the problem of missing target location information in density-based methods, which are the two mainstream dense-counting methods, a detection and counting method based on density map regression is proposed by combining the two tasks, achieving the counting and positioning of target objects in dense scenes. Complementing the advantages of two methods not only improves recall rate but also calibrates all targets. To extract richer feature information to deal with complex data scenarios, a feature pyramid optimization module is proposed, which vertically fuses low-level high-resolution features with top-level abstract semantic features and horizontally fuses same-size features to enrich the semantic expression of target objects. To address the issue of low pixel proportions occupied by target objects in dense counting scenarios, an attention mechanism for small targets is proposed to improve the network’s detection sensitivity, which can enhance the attention of the network to target objects by constructing a mask on the input image. Experimental results demonstrate that the proposed method significantly improves recall rate and accurately locates targets while maintaining accuracy, effectively providing counting and positioning information of input image, which has a wide range of application prospects in various fields such as industry and ecology.

Abstract Previous studies reported that physical activity could buffer the negative association of psychological stress with affective wellbeing. However, the studies that examined this relation in everyday life have assessed physical activity only by self-report but not with objective measures such as accelerometry. We therefore investigated the associations of both subjectively and objectively measured physical activity with stress experiences and affective wellbeing. A total of 90 university students participated in a 10-day experience sampling and diary study during their examination period and reported about stress experiences, physical activity, and affective states. Physical activity was additionally assessed using accelerometry in 50 of the participants. Subjectively assessed physical activity and objectively assessed light physical activity were associated with feeling less stressed in the evening. Also, light physical activity during the day was associated with a smaller increase/higher decrease in feeling stressed from morning to evening. The association of stress experience with negative affect was moderated by objective light physical activity. No interactive effects of stress intensity and physical activity on affective wellbeing were found. On stressful days, physical activity may buffer the negative association between stress and affective wellbeing. Particularly light physical activity as assessed with accelerometry seems to play an important role. It may be beneficial for students' affective wellbeing to increase or at least maintain physical activity during examination periods.

Circadian rhythms, the natural cycles of physical, mental, and behavioral changes that follow a roughly 24-hour cycle, are known to have a profound effect on the human body. Light plays an important role in the regulation of circadian rhythm in human body. When light from the outside enters the eyes, cones, rods, and specialized retinal ganglion cells receive the light signal and transmit it to the suprachiasmatic nucleus of the hypothalamus. The central rhythm oscillator of the suprachiasmatic nucleus regulates the rhythm oscillator of tissues all over the body. Circadian rhythms, the natural cycles of physical, mental, and behavioral changes that follow a roughly 24-hour cycle, are known to have a profound effect on the human body. As the largest organ in the human body, skin plays an important role in the peripheral circadian rhythm regulation system. Like photoreceptor cells in the retina, melanocytes express opsins. Studies show that melanocytes in the skin are also sensitive to light, allowing the skin to “see” light even without the eyes. Upon receiving light signals, melanocytes in the skin release hormones that maintain homeostasis. This process is called “photoneuroendocrinology”, which supports the health effects of light exposure. However, inappropriate light exposure, such as prolonged work in dark environments or exposure to artificial light at night, can disrupt circadian rhythms. Such disruptions are linked to a variety of health issues, emphasizing the need for proper light management in daily life. Conversely, harnessing light’s beneficial effects through phototherapy is gaining attention as an adjunctive treatment modality. Despite these advancements, the field of circadian rhythm research still faces several unresolved issues and emerging challenges. One of the most exciting prospects is the use of the skin’s photosensitivity to treat diseases. This approach could revolutionize how we think about and manage various health conditions, leveraging the skin’s unique ability to respond to light for therapeutic purposes. As research continues to unravel the complexities of circadian rhythms and their impact on health, the potential for innovative treatments and improved wellbeing is immense.

BackgroundEarly-onset androgenetic alopecia (AGA) has been associated with various chronic conditions, including metabolic syndrome (MetS). Gaining a deep understanding of early-onset AGA may enable earlier intervention in individuals at high risks. This scoping review aims to explore the risk factors and etiology, associated conditions, and adverse effects on wellbeing in early-onset AGA.MethodsElectronic literature searches were conducted in MEDLINE, EMBASE and CENTRIAL. Eligible studies included case-control, cohort, cross-sectional, and meta-analysis studies. Selected studies needed to clearly define early-onset AGA cases or include only cases starting before the age of 40 and compare them with appropriate controls. The exclusion criteria comprised editorials, commentaries, case series, and non-systematic reviews, among others. Data extraction involved collecting study characteristics, methodologies, main outcomes, and findings. Descriptive tables were used to summarize key information and relevant variables when necessary.ResultsAmong the 65 eligible articles, 67.69% were case-control studies and 78.46% evaluated only male patients. "Early-onset" was defined as cases developing before the age of 30 years in 43.08% of the studies. The Hamilton-Norwood scale was the most frequently used method for evaluating the severity of alopecia in men (69.23%). Reported risk factors for early-onset AGA included a family history of AGA, cigarette smoking, unhealthy dietary habits, and a high body mass index. Early-onset AGA may also be associated with hormonal profiles, 5α-reductase enzyme activity, androgen receptor genes, and some susceptibility loci. Comorbidities investigated included MetS, cardiovascular disease, insulin resistance, dyslipidemia, and Parkinson's disease. Men with early-onset AGA may have reduced treatment efficacy with drug like rosuvastatin, metformin or lisinopril for dyslipidemia, prediabetes, or hypertension. Additionally, young men with AGA tended to suffer from psychological issues such as anxiety and low self-esteem compared to those without hair loss.ConclusionEarly-onset AGA is a complex condition with various risk factors and etiology, associated comorbidities, and potential implications for treatment response and psychological health.

Abstract Objective We aimed to estimate the prevalence of CRFs and investigate its associated social-economic factors among adults in coastal areas of Qinzhou, Guangxi. Methods A representative sample of 1836 participants aged 20 to 70 years was included in Qinzhou, Guangxi in 2020. Data were collected by the questionnaire, anthropometric and laboratory measurements. The prevalence of CRFs, including hypertension, dyslipidemia, diabetes, overweight or obesity, alcohol consumption, and smoking were calculated by standardization. The multivariate logistic regression analysis was performed to explore the independent factors associated with the presence of CRFs. Results The age-standardized prevalence of hypertension, dyslipidemia, diabetes, overweight or obesity alcohol consumption, and smoking was 42.7%, 39.5%, 0.9%, 38.5%, 18.4% and 15.7%, respectively. The prevalence of clustering of at least one and at least two cardiovascular disease risk factors were 82.2% and 45.3% in total. There were differences in the aggregation of cardiovascular risk factors among different age, education, and income levels. There appeared higher clustering of at least one and at least two CRFs among adults with lower education level, higher income level and those elderly. Conclusions Compared with other regions in China, a higher prevalence of CRFs exists among adults in Guangxi and several social-economic factors were associated with the presence of CRFs. These findings suggest that we should implement effective measures to control the CRFs, to reduce the risk of cardiovascular disease in adults.

Given the difficulties of degrading benzotriazole (BTA), this study used a one-pot hydrothermal method to prepare α-Fe2O3/Cu2O (FC) composites for photoelectrocatalytic (PEC) degradation of BTA. The characterization of FC structure showed that Cu2O in cubic crystals was loaded with circular sheets of Fe2O3. Owing to this structure, FC showed efficient PEC degradation of BTA when exposed to ultraviolet light. The experimental results demonstrated that FC efficiently degraded BTA. When the PEC degradation continued for 60 min, 100% degradation of BTA was achieved because FC enhanced the photoelectron-hole separation and the separation and transfer of articulated carriers. High performance liquid chromatography–mass spectrometry showed that intermediates formed during the PEC degradation of BTA. Finally, various pathways for degradation of BTA were postulated. This FC-based PEC system provides a harmless and effective method for degradation of BTA.

Alopecia areata (AA) is an inflammatory autoimmune disease characterized by non-scarring hair loss on the scalp or any other part of the hair-bearing skin. While the collapse of the immune privilege is considered as one of the most accepted theories accounting for AA, the exact pathogenesis of this disease remains unclear by now. Other factors, such as genetic predisposition, allergies, microbiota, and psychological stress, also play an important role in the occurrence and development of AA. Oxidative stress (OS), an unbalance between the oxidation and antioxidant defense systems, is believed to be associated with AA and may trigger the collapse of hair follicle-immune privilege. In this review, we examine the evidence of oxidative stress in AA patients, as well as the relationship between the pathogenesis of AA and OS. In the future, antioxidants may play a new role as a supplementary therapy for AA.

Establishing reliable and reproducible animal models for disease modelling, drug screening and the understanding of disease susceptibility and pathogenesis is critical. However, traditional animal models differ significantly from humans in terms of physiology, immune response, and pathogenesis. As a result, it is difficult to translate laboratory findings into biomedical applications. Although several animal models with human chimeric genes, organs or systems have been developed in the past, their limited engraftment rate and physiological functions are a major obstacle to realize convincing models of humans. The lack of human transplantation resources and insufficient immune tolerance of recipient animals are the main challenges that need to be overcome to generate fully humanized animals. Recent advances in gene editing and pluripotent stem cell-based xenotransplantation technologies offer opportunities to create more accessible human-like models for biomedical research. In this article, we have combined our laboratory expertise to summarize humanized animal models, with a focus on hematopoietic/immune system and liver. We discuss their generation strategies and the potential donor cell sources, with particular attention given to human pluripotent stem cells. In particular, we discuss the advantages, limitations and emerging trends in their clinical and pharmaceutical applications. By providing insights into the current state of humanized animal models and their potential for biomedical applications, this article aims to advance the development of more accurate and reliable animal models for disease modeling and drug screening.

Abstract Background Vibrio cholerae O1/O139 were the predominant circulating serogroups exhibiting multi-drug resistance (MDR) during the cholera outbreak which led to cholera treatment failures. Objective This meta-analysis aimed to evaluate the weighted pooled resistance (WPR) rates in V. cholerae O1/O139 isolates obtained from environmental samples. Methods We systematically searched the articles in PubMed, Scopus, and Embase (until January 2020). Subgroup analyses were then employed by publication year, geographic areas, and the quality of studies. Statistical analyses were conducted using STATA software (ver. 14.0). Results A total of 20 studies investigating 648 environmental V. cholerae O1/O139 isolates were analysed. The majority of the studies were originated from Asia (n = 9). In addition, a large number of studies (n = 15 i.e. 71.4%) included in the meta-analysis revealed the resistance to cotrimoxazole and ciprofloxacin. The WPR rates were as follows: cotrimoxazole 59%, erythromycin 28%, tetracycline 14%, doxycycline 5%, and ciprofloxacin 0%. There was increased resistance to nalidixic acid, cotrimoxazole, furazolidone, and tetracycline while a decreased resistance to amoxicillin, ciprofloxacin, erythromycin, chloramphenicol, ampicillin, streptomycin, and ceftriaxone was observed during the years 2000–2020. A significant decrease in the doxycycline and ciprofloxacin-resistance rates in V. cholerae O1/O139 isolates was reported over the years 2011–2020 which represents a decrease in 2001–2010 (p

Introduction Previous qualitative and cross-sectional research has identified a strong sense of mental defeat in people with chronic pain who also experience the greatest levels of distress and disability. This study will adopt a longitudinal experience sampling design to examine the within-person link between the sense of mental defeat and distress and disability associated with chronic pain.Methods and analysis We aim to recruit 198 participants (aged 18–65 years) with chronic pain, to complete two waves of experience sampling over 1 week, 6 months apart (time 1 and time 2). During each wave of experience sampling, the participants are asked to complete three short online surveys per day, to provide in-the-moment ratings of mental defeat, pain, medication usage, physical and social activity, stress, mood, self-compassion, and attention using visual analogue scales. Sleep and physical activity will be measured using a daily diary as well as with wrist actigraphy worn continuously by participants throughout each wave. Linear mixed models and Gaussian graphical models will be fit to the data to: (1) examine the within-person, day-to-day association of mental defeat with outcomes (ie, pain, physical/social activity, medication use and sleep), (2) examine the dynamic temporal and contemporaneous networks of mental defeat with all outcomes and the hypothesised mechanisms of outcomes (ie, perceived stress, mood, attention and self-compassion).Ethics and dissemination The current protocol has been approved by the Health Research Authority and West Midlands—Solihull Research Ethics Committee (Reference Number: 17/WM0053). The study is being conducted in adherence with the Declaration of Helsinki, Warwick Standard Operating Procedures and applicable UK legislation.

Rational cropping maintains high soil fertility and a healthy ecosystem. Soil microorganism is the controller of soil fertility. Meanwhile, soil microbial communities also respond to different cropping patterns. The mechanisms by which biotic and abiotic factors were affected by different cropping sequences remain unclear in the major grain-producing regions of northeastern China. To evaluate the effects of different cropping sequences under conventional fertilization practices on soil properties, microbial communities, and crop yield, six types of plant cropping systems were performed, including soybean monoculture, wheat-soybean rotation, wheat-maize-soybean rotation, soybean-maize-maize rotation, maize-soybean-soybean rotation and maize monoculture. Our results showed that compared with the single cropping system, soybean and maize crop rotation in different combinations or sequences can increase soil total organic carbon and nutrients, and promote soybean and maize yield, especially using soybean-maize-maize and maize-soybean-soybean planting system. The 16S rRNA and internal transcribed spacer (ITS) amplicon sequencing showed that different cropping systems had different effects on bacterial and fungal communities. The bacterial and fungal communities of soybean monoculture were less diverse when compared to the other crop rotation planting system. Among the different cropping sequences, the number of observed bacterial species was greater in soybean-maize-maize planting setup and fungal species in maize-soybean-soybean planting setup. Some dominant and functional bacterial and fungal taxa in the rotation soils were observed. Network-based analysis suggests that bacterial phyla Acidobacteria and Actinobacteria while fungal phylum Ascomycota showed a positive correlation with other microbial communities. The phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) result showed the presence of various metabolic pathways. Besides, the soybean-maize-maize significantly increased the proportion of some beneficial microorganisms in the soil and reduced the soil-borne animal and plant pathogens. These results warrant further investigation into the mechanisms driving responses of beneficial microbial communities and their capacity on improving soil fertility during legume cropping. The present study extends our understanding of how different crop rotations effect soil parameters, microbial diversity, and metabolic functions, and reveals the importance of crop rotation sequences. These findings could be used to guide decision-making from the microbial perspective for annual crop planting and soil management approaches.

Purpose Problem solving has been defined as “a goal-directed sequence of cognitive and affective operations as well as behavioural responses to adapting to internal or external demands or challenges. Studies have shown that some nurses lack rational thinking and decision-making ability to identify patients’ health problems and make clinical judgements, and have poor cognition and response to some clinical problems, easy to fall into problem-solving dilemma. This study aimed to understand the influencing factors of clinical nurses’ problem solving dilemma, to provide a basis for developing training strategies and improving the ability of clinical nurses in problem solving. Methods A qualitative research was conducted using in-depth interviews from August 2020 to December 2020. A total of 14 participants from a tertiary hospital in Shanghai, China were recruited through purposive sampling combined with a maximum variation strategy. Data were analysed with the conventional content analysis method. Results Three themes and seven subthemes were extracted: nurse’s own factors (differences in knowledge structure and thinking, differences in professional values, poor strain capacity); improper nursing management (low sense of organizational support, contradiction between large workload and insufficient manpower allocation); patient factors (the concept of emphasizing medicine and neglecting to nurse, individual differences of patients). Conclusion The influencing factors of clinical nurses’ problem-solving dilemma are diverse. Hospital managers and nursing educators should pay attention to the problem-solving of clinical nurses, carry out a series of training and counselling of nurses by using the method of situational simulation, optimize the nursing management mode, learn to use new media technology to improve the credibility of nurses to provide guarantee for effective problem-solving of clinical nurses.

Primary cardiac tumors in children are exceedingly rare overall, which benign account for most part. The onset of the disease is occult, while the clinical manifestations are non-specific-patients may be asymptomatic or show a range of obstructive, arrhythmic, embolic or systemic symptoms. The clinical presentations generally depend on the tumors’ size, localization, and pace of growth of the tumor. Moreover, the diagnosis needs comprehensive judgment based on imaging results and pathological examination. With advances in cardiac imagining and the introduction of cardiopulmonary support, the diagnosis and treatment of these rare tumors have improved the prognosis and outlook for benign tumors. To sum up the above, we sought to integrate articles from recent years for the latest comprehensive review of the clinical manifestations, imaging characteristics, clinic pathologic features and treatment of benign cardiac tumors in children to provide a broader idea for pediatricians to recognize and treat such diseases.

BackgroundWe aimed to assess the efficacy of the artificial liver support system (ALSS) in pediatric acute liver failure (PALF) patients and to examine the risk factors associated with the effect of ALSS. Similar data are limited in PALF.MethodsAll patients diagnosed with PALF who received ALSS from June 2011 to June 2021 in the pediatric intensive care unit of the First Hospital of Jilin University were included in this retrospective cohort analysis. The effect of ALSS was measured using difference tests before and after treatments. The risk factors associated with the effect of ALSS were evaluated according to whether the total bilirubin (TBIL) and serum ammonia decreased after ALSS (TBIL-unresponsive group vs. TBIL-responsive group, serum ammonia-unresponsive group vs. serum ammonia-responsive group).ResultsThirty-nine patients who received ALSS during the study period were eligible for inclusion. The most common cause of PALF was undetermined causes (n = 14, 35.9%) followed by infection (n = 11, 28.2%). Four patients received pediatric liver transplantation. The overall survival rate was 76.9% (30/39). Fifteen (38.4%) patients received only one modality, whereas 61.6% patients received hybrid treatments. The most commonly used modality of ALSS was plasma exchange combined with continuous renal replacement therapy (n = 14, 35.9%). Alanine aminotransferase, TBIL, the international normalized ratio, and serum ammonia were significantly decreased after ALSS (P

AIM:To analyze curative effect of phacoemulsification through clear corneal tunnel incision on cataract and the influences on subjective sylptols of dry eye questionnaire scores(SDES)and break-up time(BUT).METHODS: During the period from June 2015 to January 2019, 117 cataract patients(139 eyes)who underwent cataract surgery in the hospital were divided into group A(n=65, 72 eyes)and group B(n=52, 67 eyes)by random number table method. Groups A and B underwent phacoemulsification through 2.2mm and 3.0mm micro-incision, respectively. The general surgical status, SDES, BUT and curative effect indexes [best corrected visual acuity(BCVA), spherical equivalent(SE), endothelial cell density(ECD)] were compared between the two groups.RESULTS: There was no significant difference in ultrasound time, cumulative released energy, operation time or postoperative complications between two groups(P>0.05). After surgery, SDES scores in both groups were significantly increased, BUT was decreased compared with that at 1d before surgery. At 3mo after surgery, SDES and BUT recovered to preoperative levels. At 1d and 1wk after surgery, SDES score in group A was significantly lower than that in group B, while BUT was significantly higher than that in group B(P0.05). CONCLUSION:The curative effect of phacoemulsification through clear corneal tunnel incision is reliable on cataract. The tear film function is better through 2.2mm micro-incision.

BackgroundThis study aimed to examine the relationship between the timing of physical activity and within-individual differences in depressive symptoms, positive affect, and negative affect in individuals with different baseline levels of depressive symptoms.MethodsExperience sampling methodology (ESM) was used to measure real-time depressive symptoms, positive affect, and negative affect in a convenience sample of 78 healthy adults (aged M = 25.46 years, SD = 6.18; 57 females) five times per day for 14 days. We measured physical activity throughout the 14 days by using activity sensors. Baseline levels of depressive symptoms were assessed with the PHQ-9 to build subgroups with low vs. mild-moderate depressive symptoms.ResultsPhysical activity predicted decreased depressive symptom levels, negative affect, and increased positive affect. Associations were stronger for individuals with higher baseline levels of depressive symptoms and for physical activity between 0 and 30 min compared to physical activity between 30 and 180 min before the mood rating. Conversely, levels of depressive symptoms, positive and negative affect did not predict physical activity.LimitationsThe convenience sample may not have been representative of the general population or people with depression. Accelerometers may not have detected some types of physical activities such as bicycling. Causality could not be inferred because of the observational study design.ConclusionIndividuals with higher levels of depressive symptoms may benefit from physical activity. While the effects were strongest for physical activity immediately before the mood ratings, the effects were in the same direction for up to 3 h before the mood ratings.

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple systems with various clinical manifestations. Renal involvement is common, but intracardiac thrombus is rarely reported as a complication of antiphospholipid syndrome (APS, also known as anticardiolipin syndrome). Anticoagulant therapy is the first-line treatment, and surgery is performed in severe cases. We report a case to improve clinicians’ understanding of disease diagnosis. Case presentation An 8-year-old girl was admitted to our hospital because of left costal pain, hematuria and fever. She had obvious edema occult blood 3+, urinary protein 3.2 g/24 h, albumin 17.6 g/L, and total cholesterol 7.21 mmol/L, consistent with a diagnosis of nephrotic syndrome. We continued to track the etiology of nephrotic syndrome and performed a renal biopsy, showing dsDNA 1:10 positivity, low C3, low platelets and hemoglobin, anticardiolipin IgM 12 U/ml, anti-β2-glycoprotein I (β2GPI) 223 U/ml; renal pathology suggested lupus nephritis (LN), and the patient was ultimately diagnosed with SLE, secondary APS and LN. The patient was treated with hormones and immunosuppressants. Sixteen weeks later, her urinary protein was 1+, and the quantity of urine protein was less than 0.5 g/d. Echocardiography showed that the mass in the right atrium was thrombotic. Heparin anticoagulant therapy was effective. Conclusion SLE can involve multiple systems and various complications. Thrombus in the right atrium is a rare complication of APS. Early diagnosis and treatment are key to improving the prognosis of children.

Abstract Background The efficacy and safety of spinal anesthesia by intrathecal dexmedetomidine (DEX) for parturients undergoing cesarean section are still lack of evidence. This aim of our study was to evaluate the efficacy and safety of intrathecal DEX for parturients undergoing cesarean section to provide more data evidence for intrathecal applications. Methods Three hundred parturients undergoing cesarean section under spinal anesthesia were randomly assigned into three groups: group B: 9.0 mg (1.2 ml) of 0.75% bupivacaine with saline (1 ml); group FB: 9.0 mg (1.2 ml) of 0.75% bupivacaine with 20 μg of fentanyl (1 ml); group DB: 9.0 mg (1.2 ml) of 0.75% bupivacaine with 5 μg of DEX (1 ml). Intraoperative block characteristics, parturients’ postoperative quality of recovery, maternal and neonatal outcomes and the plasma concentration of DEX were measured. All parturients were followed up for 30 days to determine whether nerve injury occurred. Results Compared with group B, the duration of sensory block in group FB and group DB were significantly prolonged (108.4 min [95% Confidence Interval (CI) = 104.6–112.3] in group B, and 122.0 min [95% CI = 116.8–127.3] in group FB, 148.2 min [95% CI = 145.3–151.1] in group DB). The overall score of quality recovery in group DB (71.6 [95% CI = 71.0–72.2]) was significantly higher than that in group FB (61.5 [95% CI = 60.8–62.2]) and group B (61.7 [95% CI = 61.0–62.4]). There was no statistically significant difference among the three groups for PH, PaO2, and PaCO2 of newborn. The plasma concentration of DEX in umbilical artery and umbilical vein was low and cannot be detected. The 30-days follow-up of parturients did not show any new onset of back, buttock or leg pain or paresthesia. Conclusions DEX is a potential local anesthetic adjuvant that the intrathecal combination of 5 μg DEX can safely exhibit a facilitatory block effect and improve parturients’ recovery quality. Trial registration Chinese Clinical Trial Registry (Registration number # ChiCTR1900022019 ; Date of Registration on March 20th, 2019).

Abstract Background Pediatric acute liver failure is a rare, life-threatening illness. Mushroom poisoning is a rare etiology. For patients with irreversible pediatric acute liver failure, liver transplantation is the ultimate lifesaving therapy. However, it is difficult to determine the optimal timing of transplantation. Here, we present a case of pediatric acute liver failure due to mushroom poisoning in northeastern China. He was treated with liver transplantation and recovered. To our knowledge, there are few reports about liver transplantation for pediatric acute liver failure caused by mushroom poisoning in mainland China. Case presentation The patient was a previously healthy 9-year-old boy who gradually developed nausea, vomiting, jaundice and coma within 5 days after ingesting mushrooms. He was diagnosed with mushroom poisoning and acute liver failure. He was treated with conservative care but still deteriorated. On the 7th day after poisoning, he underwent LT due to grade IV hepatic encephalopathy. Twenty days later, he recovered and was discharged. A review of the literature revealed that the specific criteria and optimal timing of transplantation remain to be determined. Conclusions Patients with pediatric acute liver failure should be transferred to a center with a transplant unit early. Once conservative treatment fails, liver transplantation should be performed.

Abstract Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder. Typically, it is characterized by hirsutism, hyperandrogenism, ovulatory dysfunction, menstrual disorders and infertility. To date, its pathogenesis remains unclear. However, insulin resistance (IR) is considered as the primary pathological basis for its reproductive dysfunction. On the other hand, a condition in which insulin is over-secreted is called hyperinsulinemia. IR/Hyperinsulinemia is associated with chronic inflammation, hormonal changes, follicular dysplasia, endometrial receptivity changes, and abortion or infertility. Additionally, it increases incidence of complications during pregnancy and has been associated with anxiety, depression, and other psychological disorders. Gut microbiota, the “second genome” acquired by the human body, can promote metabolism, immune response through interaction with the external environment. Gut microbiota dysbiosis can cause IR, which is closely linked to the occurrence of PCOS. This article reviewed recent findings on the roles of gut microbiota in the development of insulin resistance and the mechanism underlying polycystic ovary syndrome.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and chronic inflammation. The etiology and pathogenesis of SLE are complicated in which dysfunction of CD4+ T cells is largely engaged. In this study, we investigated the manners of CD4+ T cells in antibody production in a lupus-like mouse model through peritoneal injection of pristane reagent. With the increase in total IgG/IgM and autoantibody production after 6 months, CD4+ T cells exhibited activated phenotypes with the elevated CD44, ICOS, OX40, and PD-1 expression. Pristane injection induced the increase in IgM levels in both wild-type and T cell-deficient TCRα-/- mice whereas IgG, IgG1, and IgG2a production was impaired. When adoptively transferring CD4+ T cells into T cell-deficient mice or coculturing CD4+ T cells and B cells in vitro, it was found that CD4+ T cells derived from pristane-treated mice could help the production of total IgG as well as IgG1/IgG2a in a more efficient manner both in vivo and in vitro. While MHC was dispensable for IgG production, ICAM-1 likely functioned as an attenuating factor for IgG production. Our study thus reveals that CD4+ T cells in pristane-treated mice play important roles in IgG production, which implies the critical roles in the induction of pathological autoantibodies in MHC-independent and ICAM-1-dependent manners.

Objectives: The objective of this study was to explore the diagnostic value of deep learning-based image reconstruction (DLR) and hybrid iterative reconstruction (HIR) for calcification-related obstructive coronary artery disease (CAD) evaluation by using coronary CT angiography (CCTA) images and subtraction CCTA images.Methods: Forty-two consecutive patients with known or suspected coronary artery disease who underwent coronary CTA on a 320-row CT scanner and subsequent invasive coronary angiography (ICA), which was used as the reference standard, were enrolled. The DLR and HIR images were reconstructed as CTADLR and CTAHIR, and, based on which, the corresponding subtraction CCTA images were established as CTAsDLR and CTAsHIR, respectively. Qualitative images quality comparison was performed by using a Likert 4 stage score, and quantitative images quality parameters, including image noise, signal-to-noise ratio, and contrast-to-noise ratio were calculated. Diagnostic performance on the lesion level was assessed and compared among the four CCTA approaches (CTADLR, CTAHIR, CTAsDLR, and CTAsHIR).Results: There were 166 lesions of 86 vessels in 42 patients (32 men and 10 women; 62.9 ± 9.3 years) finally enrolled for analysis. The qualitative and quantitative image qualities of CTAsDLR and CTADLR were superior to those of CTAsHIR and CTAHIR, respectively. The diagnostic accuracies of CTAsDLR, CTADLR, CTAsHIR, and CTAHIR to identify calcification-related obstructive diameter stenosis were 83.73%, 69.28%, 75.30%, and 65.66%, respectively. The false-positive rates of CTAsDLR, CTADLR, CTAsHIR, and CTAHIR for luminal diameter stenosis ≥50% were 15%, 31%, 24%, and 34%, respectively. The sensitivity and the specificity to identify ≥50% luminal diameter stenosis was 90.91% and 83.23% for CTAsDLR.Conclusion: Our study showed that deep learning–based image reconstruction could improve the image quality of CCTA images and diagnostic performance for calcification-related obstructive CAD, especially when combined with subtraction technique.

Although several types of human skin substitutes are currently available, they usually do not include important skin appendages such as hair follicles and sweat glands, or various skin-related cells, such as dermal adipocytes and sensory neurons. This highlights the need to improve the in vitro human skin generation model for use as a tool for investigating skin diseases and as a source of cells or tissues for skin regeneration. Skin organoids are generated from stem cells and are expected to possess the complexity and function of natural skin. Here, we summarize the current literatures relating to the “niches” of the local skin stem cell microenvironment and the formation of skin organoids, and then discuss the opportunities and challenges associated with multifunctional skin organoids.

Background: Traditional Chinese medicine is promising for managing challenging and complex disorders, including cancer, and in particular, saffron is applied in treating various cancer types. However, its potential therapeutic efficacy and active components in managing squamous cell carcinoma of the head and neck (HNSCC) remain unclear yet. Methods: Using network pharmacology approaches, active ingredients of saffron, their target genes, and HNSCC-related genes were identified. Enrichment analyses were conducted for determining molecular functions and pathways enriched by genes that overlapped between the saffron target gene set and the HNSCC gene set. Among the four known active ingredients of saffron, crocetin was found to have the strongest inhibitory impact on HNSCC, based on the findings of cell viability and migration assays. Therefore, the potential target genes of crocetin in HNSCC cells were examined using molecular docking experiments and were confirmed by qPCR. Results: Four active ingredients of saffron and 184 of their target genes were identified. Further, a total of 34 overlapping saffron-/HNSCC-associated targets related to the four active ingredients were screened, and crocetin was chosen for further investigation because it had the strongest inhibitory effect on HNSCC cells. Molecular docking experiments indicated that ESR1 and CCND1 were the target genes of crocetin. These results were confirmed through qPCR analysis, in which crocetin was found to lower the expression of the ESR1 and CCND1 genes in AMC-HN-8 and FaDu cells. Conclusion: According to our results, crocetin is a primary active anti-cancer component of saffron that may have potential in the development of novel HNSCC-treating medications. However, more thorough molecular research is necessary for confirming these results and elucidating the anti-cancer mechanism underlying saffron. [ABSTRACT FROM AUTHOR]

Abstract Introduction Multiple studies have shown that diaphragmatic ultrasound can better predict the outcome of weaning in adults. However, there are few studies focusing on children, leading to a lack of sufficient clinical evidence for the application of diaphragmatic ultrasound in children. The purpose of this study was to investigate the predictive value of diaphragm ultrasound for weaning outcomes in critically ill children. Methods The study included 50 cases whose mechanical ventilation (MV) time was > 48 h, and all eligibles were divided into either the weaning success group (n = 39) or the weaning failure group (n = 11). Diaphragm thickness, diaphragmatic excursion (DE), and diaphragmatic thickening fraction (DTF) were measured in the zone of apposition. The maximum inspiratory pressure (PImax) was also recorded. Results The ventilatory treatment time (P = 0.002) and length of PICU stay (P = 0.013) in the weaning failure group was longer than the success group. Cut-off values of diaphragmatic measures associated with successful weaning were ≥ 21% for DTF with a sensitivity of 0.82 and a specificity of 0.81, whereas it was ≥0.86 cm H2O/kg for PImax with a sensitivity of 0.51 and a specificity of 0.82. The linear correlation analysis showed that DTF had a significant positive correlation with PImax in children (P = 0.003). Conclusions Diaphragm ultrasound has potential value in predicting the weaning outcome of critically ill children. DTF and PImax presented better performance than other diaphragmatic parameters. However, DE has limited value in predicting weaning outcomes of children with MV. Trial registration Current Controlled Trials ChiCTR1800020196, (Dec 2018).

Abstract Background Increasing studies have focused on motor function/dysfunction in PICU survivors; however, most studies have focused on adults and older children. This study investigated gross motor developmental function outcomes in infantile and toddler pediatric intensive care unit (PICU) survivors and the factors associated with gross motor developmental functions. Methods This observational study was conducted in the PICU of the First Hospital of Jilin University between January 2019 and March 2019. Thirty-five eligible patients were divided into the dysfunctional (n = 24) or non-dysfunctional (n = 11) group according to the results of the Peabody Developmental Motor Scales, Second Edition (PDMS-2). Baseline gross motor function for all participants before PICU admission was measured via the Age and Stages Questionnaires, Third Edition (ASQ-3). The PDMS-2 was used to evaluate gross motor development function before PICU discharge. Results The gross motor developmental dysfunction incidence was 68.6%. Linear correlation analysis showed that the gross motor quotient (GMQ) was positively correlated with the pediatric critical illness score (PCIS, r = 0.621, P

Pediatric acute liver failure (PALF) due to mushroom poisoning is a rare and life-threatening disease. There is no specific treatment. Plasma exchange (PE) is often used as a bridge to the regeneration of the liver or transplantation. However, PE is limited due to an inadequate plasma supply and transfusion-related risks. The double plasma molecular adsorption system (DPMAS) can adsorb toxins, including bilirubin and inflammatory mediators. However, the DPMAS cannot improve coagulation disorders. Combining PE and the DPMAS could compensate for the shortcomings of the two techniques. A previous study showed that the combination might be more effective than using PE or the DPMAS alone in patients with mild acute-on-chronic liver failure. To the best of our knowledge, few studies combined PE and the DPMAS for the treatment of PALF due to mushroom poisoning. Here, we specifically describe our experience with PE and the DPMAS in PALF. In conclusion, our study shows that the DPMAS and PE are safe and effective in reducing the bilirubin level and improving blood coagulation in PALF due to mushroom poisoning as a bridge to transplantation or recovery.

Melanocytes produce melanin to protect the skin from UV-B radiation. Notwithstanding, the spectrum of their functions extends far beyond their well-known role as melanin production factories. Melanocytes have been considered as sensory and computational cells. The neurotransmitters, neuropeptides, and other hormones produced by melanocytes make them part of the skin’s well-orchestrated and complex neuroendocrine network, counteracting environmental stressors. Melanocytes can also actively mediate the epidermal immune response. Melanocytes are equipped with ectopic sensory systems similar to the eye and nose and can sense light and odor. The ubiquitous inner circadian rhythm controls the body’s basic physiological processes. Light not only affects skin photoaging, but also regulates inner circadian rhythms and communicates with the local neuroendocrine system. Do melanocytes “see” light and play a unique role in photoentrainment of the local circadian clock system? Why, then, are melanocytes responsible for so many mysterious functions? Do these complex functional devices work to maintain homeostasis locally and throughout the body? In addition, melanocytes have also been shown to be localized in internal sites such as the inner ear, brain, and heart, locations not stimulated by sunlight. Thus, what can the observation of extracutaneous melanocytes tell us about the “secret identity” of melanocytes? While the answers to some of these intriguing questions remain to be discovered, here we summarize and weave a thread around available data to explore the established and potential roles of melanocytes in the biological communication of skin and systemic homeostasis, and elaborate on important open issues and propose ways forward.

As a standard clinical treatment, platelet transfusion has been employed to prevent hemorrhage in patients with thrombocytopenia or platelet dysfunctions. Platelets also show therapeutic potential for aiding liver regeneration and bone healing and regeneration and for treating dermatological conditions. However, the supply of platelets rarely meets the rising clinical demand. Other issues, including short shelf life, strict storage temperature, and allogeneic immunity caused by frequent platelet transfusions, have become serious challenges that require the development of high-yielding alternative sources of platelets. Human pluripotent stem cells (hPSCs) are an unlimited substitution source for regenerative medicine, and patient-derived iPSCs can provide novel research models to explore the pathogenesis of some diseases. Many studies have focused on establishing and modifying protocols for generating functional induced platelets (iPlatelets) from hPSCs. To reach high efficiency production and eliminate the exogenous antigens, media supplements and matrix have been optimized. In addition, the introduction of some critical transgenes, such as c-MYC, BMI1, and BCL-XL, can also significantly increase hPSC-derived platelet production; however, this may pose some safety concerns. Furthermore, many novel culture systems have been developed to scale up the production of iPlatelets, including 2D flow systems, 3D rotary systems, and vertical reciprocal motion liquid culture bioreactors. The development of new gene-editing techniques, such as CRISPR/Cas9, can be used to solve allogeneic immunity of platelet transfusions by knocking out the expression of B2M. Additionally, the functions of iPlatelets were also evaluated from multiple aspects, including but not limited to morphology, structure, cytoskeletal organization, granule content, DNA content, and gene expression. Although the production and functions of iPlatelets are close to meeting clinical application requirements in both quantity and quality, there is still a long way to go for their large-scale production and clinical application. Here, we summarize the diverse methods of platelet production and update the progresses of iPlatelets. Furthermore, we highlight recent advances in our understanding of key transcription factors or molecules that determine the platelet differentiation direction.

With the rapid rise in gene-editing technology, pluripotent stem cells (PSCs) and their derived organoids have increasingly broader and practical applications in regenerative medicine. Gene-editing technologies, from large-scale nucleic acid endonucleases to CRISPR, have ignited a global research and development boom with significant implications in regenerative medicine. The development of regenerative medicine technologies, regardless of whether it is PSCs or gene editing, is consistently met with controversy. Are the tools for rewriting the code of life a boon to humanity or a Pandora’s box? These technologies raise concerns regarding ethical issues, unexpected mutations, viral infection, etc. These concerns remain even as new treatments emerge. However, the potential negatives cannot obscure the virtues of PSC gene editing, which have, and will continue to, benefit mankind at an unprecedented rate. Here, we briefly introduce current gene-editing technology and its application in PSCs and their derived organoids, while addressing ethical concerns and safety risks and discussing the latest progress in PSC gene editing. Gene editing in PSCs creates visualized in vitro models, providing opportunities for examining mechanisms of known and unknown mutations and offering new possibilities for the treatment of cancer, genetic diseases, and other serious or refractory disorders. From model construction to treatment exploration, the important role of PSCs combined with gene editing in basic and clinical medicine studies is illustrated. The applications, characteristics, and existing challenges are summarized in combination with our lab experiences in this field in an effort to help gene-editing technology better serve humans in a regulated manner. Current preclinical and clinical trials have demonstrated initial safety and efficacy of PSC gene editing; however, for better application in clinical settings, additional investigation is warranted.

The aim of this study is to investigate the effect of platelet on the improvement of deteriorated liver function after liver resection. Six patients with hepatocellular carcinoma and liver cirrhosis have received the partial hepatectomy in the institution. Their Child–Pugh grade was B, and platelet count was below 7,000/µl. After hepatectomy, 20 units of platelet transfusion were carried out, liver function and side effects were investigated after 4 weeks, and the number of platelets increased to approximately 15,000/µl. Liver functions, such as aspartate transaminase (AST), alanine aminotransferase (ALT), cholinesterase (ChE), and prothrombin time, as well as albumin, recover to the same level as those before operation and 4 weeks after the operation. Any side effects were not recognized in all patients. Administration of platelets for cirrhotic patient with hepatectomy was carried with safety. But remarkable effect on the improvement of liver function was not recognized.

Summary: Melanocytes, derived from neural crest cells, are involved in melanin production. This protocol describes a method to generate induced melanocytes (iMelanocytes) from human induced pluripotent stem cells (iPSCs) using a suspension culture system, which considerably improves the differentiation efficiency. The most critical parts of this protocol are the selection of a reliable iPSC line with strong potential to differentiate into melanocytes and their stemness maintenance.For complete information on the use and generation of this protocol, please refer to our Cell Reports article, Liu el al. (2019).

ABSTRACTTo investigate the composition of human papillomavirus (HPV) types in anogenital warts (AGWs), viral nucleic acid in 110 AGWs, pooled into 11 specimen pools, were subjected to viral metagenomic analysis. After finding HPV7 in AGWs, conventional PCR screening was performed for HPV7 in other 190 individual AGW specimens. Viral metagenomic results indicated that 29 different types of HPV were recovered, with HPV11 and HPV6 showing the highest proportion of sequence reads. HPV7 was detected in 7 of 11 pools, 5 of which contained abundant HPV7 sequence reads. 24 complete genomes of HPV were acquired in viral metagenomic analysis, including 5 HPV7 genomes, based on which phylogenetic analysis and pairwise sequence comparison were conducted. PCR screening for HPV7 in other 190 individual AGW specimens revealed 25 positive cases (13.16%), of which the amplified fragments were sequenced and confirmed to be HPV7 sequences. Although HPV7 was generally found in hand warts and recently also in warts in toe webs, our data suggested that the role of HPV7 in AGW should be considered in the future clinical test and vaccine development for AGWs.

Background/Aims: Vascular muscularity is a key event in vessel remodeling during pulmonary artery hypertension (PAH). Endothelial-mesenchymal transdifferentiation (EndMT) has been increasingly reported to play a role in disease occurrence. Galectin-3, a carbohydrate-binding protein regulates cell proliferation, differentiation, migration and neovascularization. However, whether galectin-3 controls endothelial cell transdifferentiation during the development of PAH is unknown. Methods: Rats were exposed to normoxic or hypoxic conditions (fraction of inspired O2 0.10) for 21 d to establish PAH models. Hemodynamic changes were evaluated through surgery of the right jugular vein and ultrasound biomicroscopy inviVue. And vessel pathological alterations were detected by H&E staining. Galectin-3 (Gal-3)-induced pulmonary artery endothelium cell (PAEC) dynamic alterations were measured by MTT assays, Cell immunofluorescence, Flow cytometry, Real-time PCR and Western blot. Results: Our study demonstrated that Gal-3 was expressed in hypoxic pulmonary vascular adventitia and intima. The increased Gal-3 expression was responsible for hypoxic vessel remodeling and PAH development in vivo. Gal-3 was found to inhibit cell proliferation and apoptosis in cultured endothelial cells. Meanwhile endothelial cell morphology was altered and exhibited smooth muscle-like cell features as demonstrated by the expression of α-SMA after Gal-3 treatment. Gal-3 activated Jagged1/Notch1 pathways and induced MyoD and SRF. When MyoD or SRF were silenced with siRNAs, Gal-3-initiated transdifferentiation in endothelial cells was blocked as indicated by a lack of α-SMA. Conclusion: These results suggest that Gal-3 induces PAECs to acquire an α-SMA phenotype via a transdifferentiation process which depends on the activation of Jagged1/Notch1 pathways that mediate MyoD and SRF expression.

Abstract Background Hepatic percutaneous microwave ablation (MWA) is usually performed in patients under conscious sedation. Nonetheless, many patients reported pain during the procedure. The current study investigated the safety and effectiveness of analgesia given at personalized dosage during the MWA procedure. Methods A total of 100 patients with hepatocellular carcinomas (HCCs) were included in this study. These patients underwent CT-guided percutaneous MWA between February and October 2017. Patients were randomized into two groups: Experimental group (n = 50) and Control group (n = 50). Patients in the Control group were given 5 mg of morphine intravenously, followed by 10 mg of morphine injected subcutaneously 30 min before surgery. Patients in the Experimental group were given a personalized dosage of morphine during the procedure when the Visual Analogue Scale (VAS) was ≥4. Other clinical and treatment parameters were also analysed. Results A significantly less amount of morphine (p

Amniotic epithelial stem cells (AESCs) are considered as potential alternatives to keratinocytes (KCs) in tissue-engineered skin substitutes used for treating skin damage. However, their clinical application is limited since similarities and distinctions between AESCs and KCs remain unclear. Herein, a transcriptomics analysis and functional evaluation were used to understand the commonalities and differences between AESCs and KCs. RNA-sequencing revealed that AESCs are involved in multiple epidermis-associated biological processes shared by KCs and show more similarity to early stage immature KCs than to adult KCs. However, AESCs were observed to be heterogeneous, and some possessed hybrid mesenchymal and epithelial features distinct from KCs. A functional evaluation revealed that AESCs can phagocytose melanosomes transported by melanocytes in both 2D and 3D co-culture systems similar to KCs, which may help reconstitute pigmented skin. The overexpression of TP63 and activation of NOTCH signaling could promote AESC stemness and improve their differentiation features, respectively, bridging the gap between AESCs and KCs. These changes induced the convergence of AESC cell fate with KCs. In future, modified reprogramming strategies, such as the use of small molecules, may facilitate the further modulation human AESCs for use in skin regeneration.

The ALK gene fusion has been identified as a new driver gene in non–small cell lung cancer (NSCLC). It includes the EML4-ALK rearrangement as a recurring event that renders the tumor sensitive to ALK tyrosine kinase inhibitor crizotinib. In addition, several other fusion partners to ALK kinase domain (eg, TFG, KLC1, and KIF5B) have been identified in NSCLC. However, clinical data relevant to response in lung cancer harboring these rare ALK translocations are not fully available. A nonsmoking Chinese male originally diagnosed with “stage Ib lung adenocarcinoma” showed metastases in regional lymph nodes, pleura, and bone 1 year after surgery. The patient refused invasive tissue biopsy, and chemotherapy was administrated, which failed as a first- and second-line treatment. We then identified a rare fusion gene of ALK and Striatin (STRN) using next-generation sequencing (NGS)–based circulating tumor DNA (ctDNA) analysis. The NGS of the patient’s originally paraffin-embedded surgical tumor samples also indicated the fusion. Reverse transcription–polymerase chain reaction and Sanger sequencing further confirmed the results. The STRN-ALK involves the fusion of exon 3 of STRN retaining a coiled-coil domain to exon 20 of ALK containing a kinase domain. The patient was treated with crizotinib and showed excellent clinical, radiographic, and molecular response. Repetitive dynamic ctDNA analysis revealed that the fraction of molecular alterations in plasma was closely associated with response to crizotinib treatment. This is the first clinical evidence involving advanced NSCLC due to a rare STRN-ALK fusion and has been effectively treated with crizotinib.

Summary: Induced pluripotent stem cells (iPSCs) are a promising melanocyte source as they propagate indefinitely and can be established from patients. However, the in vivo functions of human iPSC-derived melanocytes (hiMels) remain unknown. Here, we generated hiMels from vitiligo patients using a three-dimensional system with enhanced differentiation efficiency, which showed characteristics of human epidermal melanocytes with high sequence similarity and involved in multiple vitiligo-associated signaling pathways. A modified hair follicle reconstitution assay in vivo showed that MITF+PAX3+TYRP1+ hiMels were localized in the mouse hair bulb and epidermis and produced melanin up to 7 weeks after transplantation, whereas MITF+PAX3+TYRP1− hiMelanocyte stem cells integrated into the bulge-subbulge regions. Overall, these data demonstrate the long-term functions of hiMels in vivo to reconstitute pigmented hair follicles and to integrate into normal regions for both mature melanocytes and melanocyte stem cells, providing an alternative source of personalized cellular therapy for depigmentation. : Liu et al. show that patient iPSC-derived melanocytes maintain long-term functionality in mice by integrating into regions normally containing mature melanocytes and melanocyte stem cells and reconstituting pigmented hair follicles. These insights provide an alternative source for personalized cellular therapy for depigmentation. Keywords: patient induced pluripotent stem cells, iPSCs, human iPSC-derived melanocytes, hiMels, hair follicle reconstitution in vivo, embryoid body, EB, three-dimensional differentiation system, 3D differentiation system, cellular transplantation therapy, vitiligo, melanocyte stem cells, hair follicle stem cells, human epidermal melanocytes

Humic substances are important indicators of soil fertility. The fluorescence properties of humic acids from black soils in Harbin, northeast China, were investigated, after long-term fertilization using treatments with or without mineral fertilizer (NPK) and organic manure. Excitation and emission matrices combined with parallel factor analysis were used to investigate the structure of the humic acid. Principal component analysis was performed to select the most suitable parameters for the description of humic acid. The dimension reduction for the original fluorescence parameters extracted two principal components. By using the two principal component scores as a new index for clustering, it was concluded that long-term fertilization treatments in black soil in Harbin clustered into three groups of manure + NPK and organic manure treatments, NPK treatment, and soil without any fertilization. Manure + NPK fertilization and manure fertilization alone led to a higher degree of humification than NPK only or the control. We conclude that long-term fertilization with organic matter with or without NPK could increase the humification degree of these soils.

Background: This study aimed to examine the relationship between the timing of physical activity and within-individual differences in depressive symptoms, positive affect, and negative affect in individuals with different baseline levels of depressive symptoms. Methods: Experience sampling methodology (ESM) was used to measure real-time depressive symptoms, positive affect, and negative affect in a convenience sample of 78 healthy adults (aged M = 25.46 years, SD = 6.18; 57 females) five times per day for 14 days. We measured physical activity throughout the 14 days by using activity sensors. Baseline levels of depressive symptoms were assessed with the PHQ-9 to build subgroups with low vs. mild-moderate depressive symptoms. Results: Physical activity predicted decreased depressive symptom levels, negative affect, and increased positive affect. Associations were stronger for individuals with higher baseline levels of depressive symptoms and for physical activity between 0 and 30 min compared to physical activity between 30 and 180 min before the mood rating. Conversely, levels of depressive symptoms, positive and negative affect did not predict physical activity. Limitations: The convenience sample may not have been representative of the general population or people with depression. Accelerometers may not have detected some types of physical activities such as bicycling. Causality could not be inferred because of the observational study design. Conclusion: Individuals with higher levels of depressive symptoms may benefit from physical activity. While the effects were strongest for physical activity immediately before the mood ratings, the effects were in the same direction for up to 3 h before the mood ratings. [ABSTRACT FROM AUTHOR]