Ultrasound findings and specific intrinsic blood volume expansion therapy for neonatal capillary leak syndrome: report from a multicenter prospective self-control study.

OBJECTIVE: Capillary leak syndrome (CLS) is characterized by severe systemic edema without specific treatment, resulting in a high mortality rate. This study investigated whether there is organ edema in neonatal CLS patients and specific treatment strategies to improve patient prognosis. METHODS: Thirty-seven newborns diagnosed with CLS were included in this study. (1) Routine point-of-care ultrasound (POCUS) was used to identify whether the patients had visceral edema or fluid collection. (2) All patients were treated with 3% NaCl intravenously, and the clinical manifestations, laboratory indices and outcomes were compared before and after treatment. RESULTS: (1) Diffuse severe edema was found in 92.0% of the patients. (2) The POCUS examination revealed that CLS patients exhibited significant visceral edema in addition to diffuse severe edema, which included pulmonary edema in 67.6%, cerebral edema in 37.8%, severe intestinal edema in 24.3%, severe myocardial edema in 8.1%, pericardial effusion in 5.4%, pleural effusion in 29.7% and peritoneal effusion in 18.9%. Two patients (5.45%) had only myocardial edema without other manifestations. (3) Before and after the intravenous injection of 3% NaCl, there were no significant differences in the serum sodium or potassium levels of CLS patients, while the hemoglobin and hematocrit levels were significantly lower after treatment (p < 0.01). Her plasma ALB concentration and arterial pressure returned to normal levels after the treatment was completed. (4) All the patients survived, and no side effects or complications were observed during or after treatment with 3% NaCl. CONCLUSIONS: (1) In addition to diffuse severe edema, visceral edema and effusion are common and important clinical manifestations of neonatal CLS and need to be detected by routine POCUS. (2) The intravenous injection of 3% NaCl is a safe, effective and specific treatment strategy for neonatal CLS, with a survival rate of 100% and no adverse effects.

Role of Decompressive Craniectomy in the Treatment of Malignant Cerebral Venous Sinus Thrombosis: A Single Center Consecutive Case Series Study in China.

OBJECTIVE: Patients with cerebral venous sinus thrombosis (CVST) may die during the acute phase due to increased intracranial pressure and cerebral herniation. The purpose of this study was to assess the role of decompressive craniectomy in the treatment of patients with malignant CVST. METHODS: Patients who underwent decompressive craniectomy and were consequently admitted to the Critical Care Unit, Department of Neurosurgery, at Capital Medical University Xuanwu Hospital from March 2010 to January 2021 were retrospectively examined with follow-up data at 12 months. RESULTS: In total, 14 cases were reviewed, including 9 female and 5 male patients, aged 23-63 years (42.7 ± 12.3 years). Prior to surgery, all patients had a GCS score <9. 6 patients had a unilateral dilated pupil, while 4 patients had bilateral dilated pupils. According to the head computed tomography (CT), all patients had hemorrhagic infarction, and the median midline shift was 9.5 mm before surgery. Thirteen patients underwent unilateral decompressive craniectomy, and 1 patient underwent bilateral decompressive craniectomy, among whom, 9 patients underwent hematoma evacuation. Within 3 weeks of surgery, 3 cases (21.43%) resulted in death, with 2 patients dying from progressive intracranial hypertension and 1 from acute respiratory distress syndrome (ARDS). Eleven patients (78.57%) survived after surgery, of whom 4 (28.57%) patients recovered without disability at 12-month follow-up (mRS 0-1), 2 (14.29%) patients had moderate disability (mRS 2-3), and 5 (35.71%) patients had severe disability (mRS 4-5). CONCLUSIONS: Emergent decompressive craniectomy may provide a chance for survival and enable patients with malignant CVST to achieve an acceptable quality of life (QOL).

Myocardial Edema: A Rare but Specific Manifestation of Neonatal Capillary Leak Syndrome.

Capillary leak syndrome (CLS) is a rare, potentially life-threatening systemic disease with a mortality rate of more than 30%. Its major clinical manifestation and diagnostic basis are systemic hyperedema. However, we lack knowledge about the presence of severe myocardial edema in patients with CLS. If myocardial edema cannot be detected, it will become a dangerous hidden condition that threatens the safety of patient lives. With the routine application of point-of-care critical ultrasound (POC-CUS) in clinical practice, we found that 2 of 37 (5.41%) CLS patients had severe myocardial edema as the main manifestation. It is also necessary to distinguish it from myocardial noncompaction in newborn infants with severe myocardial edema. This paper will help us to have a deeper understanding and correct management of CLS and, thus, help us to improve the prognosis of patients. This article also suggests the necessity of routine implementation of POC-CUS in the neonatal intensive care unit.

A short review on environmental distribution and toxicity of the environmentally persistent free radicals.

Environmentally Persistent Free Radicals (EPFRs) are usually generated by the electron transfer of a certain radical precursor on the surface of a carrier. They are characterized with high activity, wide migration range, and relatively long half-life period. In this review, we summarized the literature on EPFRs published since 2010, including their environmental occurrence and potential cytotoxicity and biotoxicity. The EPFRs in the atmosphere are the most abundant in the environment, mainly generated from the combustion of raw materials or biochar, and the C-center types (quinones, semiquinones radicals, etc.) may exist for a relatively long time. These EPFRs can transform into other substances (such as reactive oxygen species, ROS) under the influence of environmental factors, and partly enter soil and water by wet and dry deposition of particulate matter, which may promote the generation of EPFRs in those media. The wide distribution of EPFRs in the environment may lead to their exposure to biota including humans, resulting in cytotoxicity and biotoxicity. The EPFRs can influence the normal redox process of the biota, and generate a large number of free radicals like ROS. Exposure to EPFRs may change the expression of gene and activity of metabolic enzymes, and damage the cells, as well as some organs such as the lung, trachea, and heart. However, due to the difficulty in sample extraction, identification, and quantification of the specific EPFR individuals, the toxicity and exposure evaluation of biota are still limited which merits study in the future.

Melatonin alleviates ovarian function damage and oxidative stress induced by dexamethasone in the laying hens through FOXO1 signaling pathway.

Oxidative stress can trigger follicular atresia, and decrease follicles quantity in each development stage, thereby alleviating reproductive activity. The induction of oxidative stress in chickens through intraperitoneal injection of dexamethasone is a reliable and stable method. Melatonin has been shown to mitigate oxidative stress in this model, but the underlying mechanism remains unclear. Therefore, this study aimed to investigate whether melatonin can recover aberrant antioxidant status induced by dexamethasone and the specific mechanism behind melatonin-dependent protection. A total of 150 healthy 40-wk-old Dawu Jinfeng laying hens with similar body weights and laying rates were randomly divided into three groups, with five replicates per group and 10 hens per replicate. The hens in the control group (NS) received intraperitoneal injections of normal saline for 30 d, the dexamethasone group (Dex+NS) received 20 mg/kg dose of dexamethasone for the first 15 d, followed by the 15 d of normal saline treatment. While in the melatonin group (Dex+Mel), dexamethasone (20 mg/kg dose) was injected intraperitoneally in the first 15 d, and melatonin (20 mg/kg/d) was injected in the last 15 d. The results showed that dexamethasone treatment significantly enhanced oxidative stress (P < 0.05), while melatonin not only inhibited the oxidative stress but also notably enhanced the antioxidant enzymes superoxide dismutase (SOD), catalase activity (CAT), glutathione peroxidase (GSH-Px), and antioxidant genes CAT, superoxide dismutase 1 (SOD1), glutathione peroxidase 3 (GPX3), and recombinant peroxiredoxin 3 (PRDX3) expression (P < 0.05). Melatonin treatment also markedly reduced 8-hydroxy deoxyguanosine (8-OHdG), malondialdehyde (MDA), and reactive oxygen species (ROS) levels (P < 0.05) and apoptotic genes Caspase-3, Bim, and Bax in the follicle. In the Dex+Mel group, the Bcl-2 and SOD1 protein levels were also increased (P < 0.05). Melatonin inhibited the forkhead Box Protein O1 (FOXO1) gene and its protein expression (P < 0.05). In general, this investigation revealed that melatonin might decrease oxidative stress and ROS by enhancing antioxidant enzymes and genes, activating the antiapoptotic genes, and inhibiting the FOXO1 pathway in laying hens.

Sestrin2 contributes to BRAF inhibitor resistance via reducing redox vulnerability of melanoma cells.

BACKGROUND: Treatment resistance often occurs with BRAF inhibitor (BRAFi) therapy for melanoma, bringing in a great challenge to the treatment of melanoma patients harboring mutant BRAF gene. Recent studies revealed redox vulnerability constitutes a novel opportunity to overcome BRAFi resistance. Previously we found Sestrin2 provided protection to metastatic melanoma cells by detoxifying reactive oxygen species (ROS) induced by anoikis, but its defensive role against redox stimuli elicited by BRAFi was unclear. OBJECTIVE: In-depth explored the role of Sestrin2 in BRAFi-resistant melanoma. METHODS: Vemurafenib-resistant melanoma cells were established using 451Lu and UACC62 cell lines carrying BRAFV600E mutation. Mechanistic studies were subsequently performed by transfection of lentiviral vectors encoding an shRNA against SESN2 or embedded with the coding sequences of SESN2 cDNA. RESULTS: Elevated Sestrin2 expression was found in vemurafenib-resistance melanoma cells. Further mechanistic studies revealed that BRAFi-resistant melanoma cells employ Sestrin2 to adapt to higher oxidative stress under vemurafenib exposure. It was also demonstrated that mTOR signaling was significantly activated following Sestrin2 knockdown. Given the known promoting role of active mTOR signaling in melanoma proliferation and survival, the effects of mTOR blocker and Sestrin2 ablation on BRAFi-resistant melanoma cells were further tested, and the combination was found to result in enhanced inhibition of melanoma cell growth. CONCLUSIONS: Our findings demonstrated the contribution of Sestrin2 to the development of BRAFi resistance and the fact that the combination of mTOR blocker assisted Sestrein2 ablation in eliminating BRAFi resistance of melanoma. Therefore, mTOR and Sestrin2 may be novel combinatorial therapeutic targets to overcome BRAFi resistance of melanoma.

The efficacy of PD-1 inhibitors in the maintenance treatment of diffuse large B-cell lymphoma: A single-center retrospective analysis.

Purpose: To explore the impact of PD-1 maintenance therapy on the relapse-free survival (RFS) of patients with diffuse large B-cell lymphoma (DLBCL). Methods: We retrospectively analyzed patients with DLBCL admitted to our center between January 2018 and July 2019 who achieved complete remission (CR) after induction chemotherapy. Forty-five patients who received PD-1 inhibitor maintenance therapy were considered the treatment group. Forty-five patients who did not undergo maintenance treatment during the same period were selected as the control group. The base levels of the two groups of patients were similar. The 2-year RFS rate of the two groups was compared. The correlation between the adverse prognosis factors of the patients and the RFS rate was performed subgroup analysis. Results: The 2-year RFS rates of the treatment and control groups were 86.7% VS 75.6% (P = 0.178), respectively, until July 2021. A single factor analysis showed that patients with International Prognostic Index (IPI) score ≥ 3, non-GCB DLBCL receiving PD-1 inhibitor maintenance treatment, can improve their 2-year RFS (72.2% VS 30.8%, P = 0.022; 88.5% VS 62.5%, P = 0.032). For non-GCB patients, the 2-year RFS of the treatment group can reach 88.5%, while the 2-year RFS of the control group is 62.5%, which is statistically significant (P = 0.032). In all patients treated with PD-1 inhibitors, the adverse reactions were all grade I-II, and there were no grade III-IV adverse reactions. There were no clear adverse events in the follow-up patients in the control group. Conclusion: Maintenance treatment with PD-1 inhibitors can improve the 2-year RFS rate of patients with IPI score of ≥3 and non-GCB DLBCL. This prompts the potential advantage of PD-1 inhibitors in DLBCL maintenance treatment. However, longer follow-ups remain needed to obtain more definite data.

Difference of geographic distributions of the Chinese patients with prion diseases in the permanent resident places and referring places.

Human prion diseases (PrDs) are a group of transmissible neurodegenerative diseases that can be clarified as sporadic, genetic and iatrogenic forms. In this study, we have analysed the time and geographic distributions of 2011 PrD cases diagnosed by China National Surveillance for Creutzfeldt-Jakob disease (CNS-CJD) since 2006, including 1792 sporadic CJD (sCJD) cases and 219 gPrD cases. Apparently, the cases numbers of both sCJD and gPrD increased along with the surveillance years, showing a stepping up every five years. The geographic distributions of the PrDs cases based on the permanent residences were wide, distributing in 30 out of 31 provincial-level administrative divisions in Chinese mainland. However, the case numbers in the provincial level varied largely. The provinces in the eastern part of China had much more cases than those in the western part. Normalized the case numbers with the total population each province revealed higher incidences in six provinces. Further, the resident and referring places of all PrD cases were analysed, illustrating a clear concentrating pattern of referring in the large metropolises. Five provincial-level administrative divisions reported more PrD cases from other provinces than the local ones. Particularly, BJ reported not only more than one-fourth of all PrDs cases in Chinese mainland but also 3.64-fold more PrDs cases from other provinces than its local ones. We believed that good medical resources, well-trained programmes and knowledge of PrDs in the clinicians and the CDC staffs contributed to well-referring PrD cases in those large cities.

Integrative Genomic Profiling Uncovers Therapeutic Targets of Acral Melanoma in Asian Populations.

PURPOSE: Acral melanoma is the major subtype of melanoma seen in Asian patients with melanoma and is featured by its insidious onset and poor prognosis. The genomic study that elucidates driving mutational events is fundamental to the development of gene-targeted therapy. However, research on genomic profiles of acral melanoma in Asian patients is still sparse. EXPERIMENTAL DESIGN: We carried out whole-exome sequencing (WES) on 60 acral melanoma lesions (with 55 primary samples involved), targeted deep sequencing in a validation cohort of 48 cases, RNA sequencing in 37 acral melanoma samples (all from the 60 undergoing WES), and FISH in 233 acral melanoma specimens (54 of the 60 undergoing WES included). All the specimens were derived from Asian populations. RESULTS: BRAF, NRAS, and KIT were discerned as significantly mutated genes (SMG) in acral melanoma. The detected COSMIC signature 3 related to DNA damage repair, along with the high genomic instability score, implied corresponding pathogenesis of acral melanoma. Moreover, the copy number gains of EP300 were associated with the response of acral melanoma to targeted therapy of A485 (a p300 inhibitor) and immune checkpoint blockade treatment. In addition, the temporal order in mutational processes of the samples was reconstructed, and copy-number alterations were identified as early mutational events. CONCLUSIONS: Our study provided a detailed view of genomic instability, potential therapeutic targets, and intratumoral heterogeneity of acral melanoma, which might fuel the development of personalized strategies for treating acral melanoma in Asian populations.

Lung ultrasound completely replaced chest X-ray for diagnosing neonatal lung diseases: a 3-year clinical practice report from a neonatal intensive care unit in China.

BACKGROUND AND OBJECTIVE: Lung ultrasound (LUS) has been widely used in the diagnosis and differential diagnosis of neonatal lung diseases (NLDs), but whether it can replace the routine use of chest X-ray (CXR) in neonatal intensive care units (NICUs) remains controversial. This paper summarizes the clinical practice of our neonatal intensive care unit (NICU) during the past three years to explore the feasibility and necessity of using LUS instead of CXR to diagnose NLDs in the NICU setting. METHODS: The clinical data and LUS examination results from 1,381 newborn infants with respiratory difficulty who were hospitalized in our NICU from March 2017 to February 2020 were retrospectively collected to analyze the types of lung diseases diagnosed and the reliability of LUS for diagnosing NLDs. RESULTS: (1) During this period, 1381 newborn infants with dyspnea were admitted to our NICU, accounting for 41.2% of all hospitalized children. (2) Among the 1381 infants, 17 patients with respiratory distress were confirmed as having severe heart disease by echocardiography, while the remaining 1364 patients had different kinds of lung diseases: pneumonia (697 patients, 51.1%), respiratory distress syndrome (251 patients, 17.4%), transient tachypnea of the newborn (197 patients, 13.3%), atelectasis (89 patients, 5.6%), pneumothorax (46 patients, 3.2%), pulmonary hemorrhage (69 patients, 4.5%), severe pleural effusion (18 patients, 1.32%), congenital pulmonary sequestration (3 patients, 0.22%), bullae of the lung (2 patients, 0.15%), and congenital cystic adenomatoid malformation (2 patients). (5) Among the 1381 infants, 217 received CXR examination before admission, which resulted in misdiagnosis in 45 patients (20.7%) and missed diagnosis in 12 patients (5.5%); the missed diagnosis and misdiagnosis rate was 26.3%. CONCLUSION: Our 3-year clinical practice experience indicated that LUS could completely replace chest X-ray for the diagnosis and differential diagnosis of NLDs in the NICU. Compared with X-ray, LUS had higher accuracy and reliability in diagnosing NLDs.

Predicting Chronic Myocardial Ischemia Using CCTA-Based Radiomics Machine Learning Nomogram.

BACKGROUND: Coronary computed tomography angiography (CCTA) is a well-established non-invasive diagnostic test for the assessment of coronary artery diseases (CAD). CCTA not only provides information on luminal stenosis but also permits non-invasive assessment and quantitative measurement of stenosis based on radiomics. PURPOSE: This study is aimed to develop and validate a CT-based radiomics machine learning for predicting chronic myocardial ischemia (MIS). METHODS: CCTA and SPECT-myocardial perfusion imaging (MPI) of 154 patients with CAD were retrospectively analyzed and 94 patients were diagnosed with MIS. The patients were randomly divided into two sets: training (n = 107) and test (n = 47). Features were extracted for each CCTA cross-sectional image to identify myocardial segments. Multivariate logistic regression was used to establish a radiomics signature after feature dimension reduction. Finally, the radiomics nomogram was built based on a predictive model of MIS which in turn was constructed by machine learning combined with the clinically related factors. We then validated the model using data from 49 CAD patients and included 18 MIS patients from another medical center. The receiver operating characteristic curve evaluated the diagnostic accuracy of the nomogram based on the training set and was validated by the test and validation set. Decision curve analysis (DCA) was used to validate the clinical practicability of the nomogram. RESULTS: The accuracy of the nomogram for the prediction of MIS in the training, test and validation sets was 0.839, 0.832, and 0.816, respectively. The diagnosis accuracy of the nomogram, signature, and vascular stenosis were 0.824, 0.736 and 0.708, respectively. A significant difference in the number of patients with MIS between the high and low-risk groups was identified based on the nomogram (P < .05). The DCA curve demonstrated that the nomogram was clinically feasible. CONCLUSION: The radiomics nomogram constructed based on the image of CCTA act as a non-invasive tool for predicting MIS that helps to identify high-risk patients with coronary artery disease.

Anti-NMDA receptor encephalitis: a review of mechanistic studies.

NMDA receptors (NMDARs) are ion channels gated by glutamate, the major excitatory neurotransmitter in the central nervous system. Anti-NMDA receptor (anti-NMDAR) encephalitis is an autoimmune disease characterized by the presence of autoantibodies against the NMDAR GluN1 subunit. Here we briefly review current advances in the understanding of the mechanisms underlying the pathogenesis of anti-NMDAR encephalitis. The autoantibodies bind to and cross-link the endogenous NMDARs, disrupt the interaction of NMDARs with receptor tyrosine kinase EphB2 leading to internalization and reduced function of NMDARs. Hypofunction of the NMDARs results in impairment in long-term potentiation and deficit in learning and memory, leads to development of depression-like behavior, and lowers the threshold for seizures. Recent development of active immunization models of anti-NMDAR encephalitis provides insight into the inflammation process and paves the way for further studies that may lead to better treatment.

Long Non-Coding RNA CD27-AS1-208 Facilitates Melanoma Progression by Activating STAT3 Pathway.

Melanoma is the most lethal skin cancer that originates from epidermal melanocytes. Recently, long non-coding RNAs (lncRNAs) are emerging as critical regulators of cancer pathogenesis and potential therapeutic targets. However, the expression profile of lncRNAs and their role in melanoma progression have not been thoroughly investigated. Herein, we firstly obtained the expression profile of lncRNAs in primary melanomas using microarray analysis and unveiled the differentially-expressed lncRNAs compared with nevus. Subsequently, a series of bioinformatics analysis showed the great involvement of dysregulated lncRNAs in melanoma biology and immune response. Further, we identified lncRNA CD27-AS1-208 as a novel nuclear-localized factor with prominent facilitative role in melanoma cell proliferation, invasion and migration. Mechanistically, CD27-AS1-208 could directly interact with STAT3 and contribute to melanoma progression in a STAT3-dependent manner. Ultimately, the role of CD27-AS1-208 in melanoma progression in vivo was also investigated. Collectively, the present study offers us a new horizon to better understand the role of lncRNAs in melanoma pathogenesis and demonstrates that CD27-AS1-208 up-regulation contributes to melanoma progression by activating STAT3 pathway. Targeting CD27-AS1-208 in melanoma cells can be exploited as a potential therapeutic approach that needs forward validation in clinical trials in the future.

Melatonin regulates chicken granulosa cell proliferation and apoptosis by activating the mTOR signaling pathway via its receptors.

Melatonin is a key regulator of follicle granular cell maturation and ovulation. The mammalian target of rapamycin (mTOR) pathway plays an important role in cell growth regulation. Therefore, our aim was to investigate whether the mTOR signaling pathway is involved in the regulation of melatonin-mediated proliferation and apoptotic mechanisms in granulosa cells. Chicken follicle granular cells were cultured with melatonin (0, 2, 20, or 200 µmol/L) for 48 h. The results showed that melatonin treatment enhanced proliferation and suppressed apoptosis in granular cells at 20 µmol/L and 200 µmol/L (P < 0.05) by upregulation of cyclin D1 (P < 0.01) and Bcl-2 (P < 0.01) and downregulation of P21, caspase-3, Beclin1, and LC3-II (P < 0.01). The effects resulted in the activation of the mTOR signaling pathway by increasing the expression of avTOR, PKC, 4E-BP1, S6K (P < 0.05), p-mTOR, and p-S6K. We added an mTOR activator and inhibitor to the cells and identified the optimal dose (10 µmol/L MHY1485 and 100 nmol/L rapamycin) for subsequent experiments. The combination of 20 µmol/L melatonin and 10 µmol/L MHY1485 significantly enhanced granulosa cell proliferation (P < 0.05), while 100 nmol/L rapamycin significantly inhibited proliferation and enhanced apoptosis (P < 0.05), but this action was reversed in the 20-µmol/L melatonin and 100-nmol/L rapamycin cotreatment groups (P < 0.05). This was confirmed by mRNA and protein expression that was associated with proliferation, apoptosis, and autophagy (P < 0.05). The combination of 20 µmol/L melatonin and 10 µmol/L MHY1485 also activated the mTOR pathway upstream genes PI3K, AKT1, and AKT2 and downstream genes PKC, 4E-BP1, and S6K (P < 0.05), as well as protein expression of p-mTOR and p-S6K. Rapamycin significantly inhibited the mTOR pathway-related genes mRNA levels (P < 0.05). In addition, activation of the mTOR pathway increased melatonin receptor mRNA levels (P < 0.05). In conclusion, these findings demonstrate that melatonin regulates chicken granulosa cell proliferation and apoptosis by activating the mTOR signaling pathway via its receptor.

Hydrogen agronomy: research progress and prospects.

Agriculture is the foundation of social development. Under the pressure of population growth, natural disasters, environmental pollution, climate change, and food safety, the interdisciplinary "new agriculture" is becoming an important trend of modern agriculture. In fact, new agriculture is not only the foundation of great health and new energy sources, but is also the cornerstone of national food security, energy security, and biosafety. Hydrogen agronomy focuses mainly on the mechanism of hydrogen gas (H2) biology effects in agriculture, and provides a theoretical foundation for the practice of hydrogen agriculture, a component of the new agriculture. Previous research on the biological effects of H2 focused chiefly on medicine. The mechanism of selective antioxidant is the main theoretical basis of hydrogen medicine. Subsequent experiments have demonstrated that H2 can regulate the growth and development of plant crops, edible fungus, and livestock, and enhance the tolerance of these agriculturally important organisms against abiotic and biotic stresses. Even more importantly, H2 can regulate the growth and development of crops by changing the soil microbial community composition and structure. Use of H2 can also improve the nutritional value and postharvest quality of agricultural products. Researchers have also shown that the biological functions of molecular hydrogen are mediated by modulating reactive oxygen species (ROS), nitric oxide (NO), and carbon monoxide (CO) signaling cascades in plants and microbes. This review summarizes and clarifies the history of hydrogen agronomy and describes recent progress in the field. We also argue that emerging hydrogen agriculture will be an important direction in the new agriculture. Further, we discuss several scientific problems in hydrogen agronomy, and suggest that the future of hydrogen agronomy depends on contributions by multiple disciplines. Important future research directions of hydrogen agronomy include hydrogen agriculture in special environments, such as islands, reefs, aircraft, and outer space.

Preparation of a whole cell catalyst overexpressing acetohydroxyacid synthase of Thermotoga maritima and its application in the syntheses of α-hydroxyketones.

The large catalytic subunit of acetohydroxyacid synthase (AHAS, EC 2.2.1.6) of Thermotoga maritima (TmcAHAS) was prepared in this study. It possesses high specific activity and excellent stability. The protein and a whole cell catalyst overexpressing the protein were applied to the preparation of α-hydroxyketones including acetoin (AC), 3-hydroxy-2-pentanone (HP), and (R)-phenylacetylcarbinol (R-PAC). The results show that AC and HP could be produced in high yields (84% and 62%, respectively), while R-PAC could be synthesized in a high yield (about 78%) with an R/S ratio of 9:1. Therefore, TmcAHAS and the whole cell catalyst overexpressing the protein could be practically useful bio-catalysts in the preparation of α-hydroxyketones including AC, HP, and R-PAC. To the best of our knowledge, this is the first time that bacterial AHAS was used as a catalyst to prepare HP with a good yield, and also the first time that TmcAHAS was employed to synthesize AC and R-PAC.

Two new species of Episymploce Bey-Bienko, 1950 (Blattodea, Ectobiidae, Blattellinae) from China.

Two new species of Episymploce Bey-Bienko from China are described. Nine individuals of E. sichuanensis sp. nov. were collected from Sichuan Province and four individuals of E. maxima, sp. nov. were collected from Guangxi Province. Morphology, especially the wings, specialized abdominal tergum and genitalia of adults, are described and illustrated in detail. Episymploce sichuanensis sp. nov. is similar to E. kunmingi (Bey-Bienko, 1969), but can be easily distinguished by the reduced wings, bifurcated two processes at the hind margin of the supra-anal plate, and the unspecialized first abdominal tergum (T1). Episymploce maxima sp. nov. is similar to E. taiheizana Asahina, 1979 but is distinguished by its large size, the lateromedial margins of the subgenital plate without processes, and the unspecialized T1. A key to the recorded Episymploce species from China is provided in this paper.

POU4F1 promotes the resistance of melanoma to BRAF inhibitors through MEK/ERK pathway activation and MITF up-regulation.

BRAF inhibitors (BRAFi) have shown remarkable clinical efficacy in the treatment of melanoma with BRAF mutation. Nevertheless, most patients end up with the development of BRAFi resistance, which strongly limits the clinical application of these agents. POU4F1 is a stem cell-associated transcriptional factor that is highly expressed in melanoma cells and contributes to BRAF-activated malignant transformation. However, whether POU4F1 contributes to the resistance of melanoma to BRAFi remains poorly understood. Here, we report that over-expressed POU4F1 contributed to the acquired resistance of melanoma cells to Vemurafenib. Furthermore, POU4F1 promoted the activation of ERK signaling pathway via transcriptional regulation on MEK expression. In addition, POU4F1 could increase the expression of MITF to retain the resistance of melanoma cells to BRAFi. Collectively, our findings reveal that POU4F1 re-activates the MAPK pathway by transcriptional regulation on MEK expression and promotes MITF expression, which ultimately results in the resistance to BRAFi in melanoma. Our study supports that POU4F1 is a potential combined therapeutic target with BRAFi therapy for melanoma.

International Expert Consensus and Recommendations for Neonatal Pneumothorax Ultrasound Diagnosis and Ultrasound-guided Thoracentesis Procedure.

Pneumothorax (PTX) represents accumulation of the air in the pleural space. A large or tension pneumothorax can collapse the lung and cause hemodynamic compromise, a life-threatening disorder. Traditionally, neonatal pneumothorax diagnosis has been based on clinical images, auscultation, transillumination, and chest X-ray findings. This approach may potentially lead to a delay in both diagnosis and treatment. The use of lung US in diagnosis of PTX together with US-guided thoracentesis results in earlier and more precise management. The recommendations presented in this publication are aimed at improving the application of lung US in guiding neonatal PTX diagnosis and management.

Impact of Interferon-alpha1b (IFN-α1b) on Antitumor Immune Response: An Interpretation of the Promising Therapeutic Effect of IFN-alpha1b on Melanoma.

BACKGROUND Melanoma is among the most aggressive forms of cancer. Our latest retrospective analysis showed that recombinant human interferon-alpha1b (IFN-alpha1b) led to significantly prolonged survival with mild toxicity in patients with stage IV melanoma. Based on this clinical finding, the current study sought to investigate the influence of IFN-alpha1b on the antitumor immunity of melanoma, with interferon-alpha2b (IFN-alpha2b) used as a control. MATERIAL AND METHODS Peripheral blood mononuclear cells were stimulated with culture medium alone, or medium supplemented with IFN-alpha1b or IFN-alpha2b. Flow cytometry and lactate dehydrogenase release assays were used to evaluate cytotoxic effects. Flow cytometry and enzyme-linked immunospot assays were used to analyze immunoregulatory effects on natural killer (NK) cells, natural killer T (NKT) cells, CD3⁺CD8⁺ T cells, and melanoma cells. Cell Counting Kit-8 assay was performed to measure the effect on proliferation of melanoma cells in vitro. RESULTS IFN-alpha1b enhanced the activity of NK cells, NKT cells, and CD3⁺CD8⁺ T cells from melanoma patients. Compared with IFN-alpha2b, IFN-alpha1b induced a relatively lower level of programmed cell death-ligand 1 (PD-L1) in melanoma cells without affecting the expression of PD-L1 in CD3⁺CD8⁺ T cells. Additionally, IFN-alpha1b showed a much stronger inhibition of the proliferation of melanoma cells than IFN-alpha2b. CONCLUSIONS IFN-alpha1b has an immunostimulatory activity similar to IFN-alpha2b and possesses milder adverse effects on immune checkpoints and stronger inhibitory effects on melanoma cell growth than IFN-alpha2b. Therefore, IFN-alpha1b is a promising drug for the treatment of melanoma.