Nitric oxide-induced lipophagic defects contribute to testosterone deficiency in rats with spinal cord injury.

Introduction: Males with acute spinal cord injury (SCI) frequently exhibit testosterone deficiency and reproductive dysfunction. While such incidence rates are high in chronic patients, the underlying mechanisms remain elusive. Methods and results: Herein, we generated a rat SCI model, which recapitulated complications in human males, including low testosterone levels and spermatogenic disorders. Proteomics analyses showed that the differentially expressed proteins were mostly enriched in lipid metabolism and steroid metabolism and biosynthesis. In SCI rats, we observed that testicular nitric oxide (NO) levels were elevated and lipid droplet-autophagosome co-localization in testicular interstitial cells was decreased. We hypothesized that NO impaired lipophagy in Leydig cells (LCs) to disrupt testosterone biosynthesis and spermatogenesis. As postulated, exogenous NO donor (S-nitroso-N-acetylpenicillamine (SNAP)) treatment markedly raised NO levels and disturbed lipophagy via the AMPK/mTOR/ULK1 pathway, and ultimately impaired testosterone production in mouse LCs. However, such alterations were not fully observed when cells were treated with an endogenous NO donor (L-arginine), suggesting that mouse LCs were devoid of an endogenous NO-production system. Alternatively, activated (M1) macrophages were predominant NO sources, as inducible NO synthase inhibition attenuated lipophagic defects and testosterone insufficiency in LCs in a macrophage-LC co-culture system. In scavenging NO (2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO)) we effectively restored lipophagy and testosterone levels both in vitro and in vivo, and importantly, spermatogenesis in vivo. Autophagy activation by LYN-1604 also promoted lipid degradation and testosterone synthesis. Discussion: In summary, we showed that NO-disrupted-lipophagy caused testosterone deficiency following SCI, and NO clearance or autophagy activation could be effective in preventing reproductive dysfunction in males with SCI.

Characteristics of neonatal hypoxic-ischemic encephalopathy at high altitude and early results of therapeutic hypothermia.

BACKGROUND: Altitude hypoxia and limited socioeconomic conditions may result in distinctive features of neonatal hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) has not been used at altitude. We examined characteristics of HIE and early outcomes of TH in 3 centers at two high altitudes, 2 at 2,261 m and 1 at 3,650 m. METHODS: The incidence of HIE at NICUs was noted. TH was conducted when personnel and devices were available in 2019~2020. Standard inclusion criteria were used, with the addition of admission age >6 hours and mild HIE. Demographic and clinical data included gestational age, gender, weight, Apgar score, ethnics, age on admission, age at TH and clinical degree of HIE. EEG was monitored for 96 hours during hypothermia and rewarming. MRI was performed before discharge. RESULTS: There was significant difference in ethnics, HIE degree, age at TH across 3 centers. The overall NICU incidence of HIE was 4.0%. Among 566 HIE patients, 114 (20.1%) received TH. 63 (55.3%) patients had moderate/severe HIE. Age at TH >6 hours occurred in 34 (29.8%) patients. EEG discharges showed seizures in 7~11% of patients, whereas spikes/sharp waves in 94~100%, delta brushes in 50~100%. After TH, MRI showed moderate to severe brain injury in 77% of patients, and correlated with center, demographic and clinical variables (Ps≤0.0003). Mortality was 5% during hospitalization and 11% after discharge until 1 year. CONCLUSIONS: At altitude, the incidence of HIE was high and brain injury was severe. TH was limited and often late >6 hours. EEG showed distinct patterns attributable to altitude hypoxia. TH was relatively safe. TRIAL REGISTRATION: The study was registered on February 23, 2019 in Chinese Clinical Trial Register (ChiCTR1900021481).

PRPF19 promotes the proliferation, migration, and inhibits autophagy in prostate cancer by suppressing SLC40A1.

Prostate cancer (PCa) is a common cancer and the leading cause of cancer-related death in men. To investigate the role of pre-mRNA processing factor 19 (PRPF19) in proliferation, migration of PCa, and evaluate the potential ability of PRPF19 as a therapeutic target. PRPF19 expression was analyzed from The Cancer Genome Atlas and GEPIA databank. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate the transcription of PRPF9 and solute carrier family 40 member 1 (SLC40A1). Immunohistochemistry (IHC) was used to test PRPF9 expression in PCa tissues. The cell viability and 5-ethynyl-2'-deoxyuridine incorporation analysis were performed to assess cell proliferation. Transwell assay was performed to investigate the migration and invasion of cancer cells. Western blot was used to measure the expression level of PRPF9, E-cadherin, Vimentin and α-smooth muscle actin (α-SMA), SLC40A1, LC3, Beclin-1 and ATG7. Immunofluorescence assay was performed to measure LC3 expression in PCa cells. The bioinformatic analysis revealed PRPF19 was highly expressed in PCa which was certified by qRT-PCR, western blot and IHC detection in PCa tissues. The proliferation of PCa cells could be promoted by PRPF19 overexpression and suppressed by PRPF19 knockdown. Moreover, the migration and invasion of PCa cells could be positively regulated by PRPF19 which promoted the expression of E-cadherin, Vimentin, and α-SMA. Furthermore, the expression of LC3, Beclin-1, and ATG7 was negatively regulated by PRPF19, indicating that PRPF19 inhibited autophagy in PCa cells. In the double knockdown of PRPF19 and SLC40A1, PRPF19 repressed the mRNA and reduced protein level of SLC40A1, and SLC40A1 antagonized effects of PRPF19 on proliferation, migration and autophagy of PCa cells. PRPF19 promoted proliferation and migration, and inhibited autophagy in PCa by attenuating SLC40A1 expression, indicating PRPF19 was a potential therapeutic target for PCa treatment.

Short-term prognosis of very-preterm infants of ethnic minorities and Han nationality at high altitude: a single-center, retrospective study.

OBJECTIVE: We aimed to analyze the perinatal care of very-preterm infants (VPIs) in plateau areas of China and to explore any differences in short-term outcomes between ethnic minorities and Han nationality. METHODS: VPIs with gestational age (GA) <32 weeks admitted to Qinghai Red Cross Hospital from 1 January 2018 to 31 December 2020 were enrolled. Maternal information, neonatal information, perinatal care and discharge outcomes were retrospectively collected and analyzed. RESULTS: A total of 302 VPIs were examined, including 143 (47.4%) ethnic minority infants and 159 (52.6%) Han infants. Mothers of ethnic minority infants were significantly younger than those of Han infants (27 y vs. 30 y, p < .001). There were no differences in the incidence of assisted reproduction, multiple pregnancies, maternal hypertension, clinical chorioamnionitis or premature rupture of membranes >18 h between ethnic minority mothers and Han mothers. Lower proportions of cesarean section and incidence of maternal diabetes were observed in ethnic minority mothers than in Han mothers [(9.1 vs.17.6%, p < .05) and (42.7 vs. 57.9%, p < .05, respectively)]. Meanwhile, fewer antenatal steroids were used in minority group than Han group (65.7 vs. 81.1%, p < .05). No significant differences in rates of death, active treatment, necrotizing enterocolitis stage ≥2, moderate-to-severe BPD, and incidence of severe retinopathy of prematurity in VPIs were found between the two groups and in all GA subgroups. Severe neurological injury was significantly less common in the minority newborns than in the Han infants (1.2 vs. 6.1%, p < .05). Compared with Han group, no excess risk of death, death or major morbidity, death despite active treatment, death or major morbidity despite active treatment was observed in ethnic minorities, with or without adjusting for gestational age and prenatal steroids. CONCLUSIONS: Short-term prognosis of VPIs of ethnic minorities were similar to those of Han nationality.

Chylothorax and chylopericardial tamponade following lobectomy and lymphadenectomy: a rare presentation.

BACKGROUND: Although postoperative chylothorax following lung cancer surgery is rare, it is a recognized complication in 0.25-3% of patients. However, cases of cardiac tamponade caused by chylopericardium after lung cancer surgery are extremely rare. CASE PRESENTATION: We describe hitherto unreported sequelae of chyle leak following lobectomy and systematic mediastinal lymph node dissection (SLND) causing pericardial tamponade and cardiovascular compromise. The patient was successfully treated with minimally invasive surgical repair and ligation. We also discuss the development of chylopericardium as a potential complication of lobectomy and SLND. CONCLUSIONS: The anatomical characteristics of the thoracic duct warrant special attention in postoperative chyle leak management in patients who undergo definitive mediastinal lymph node dissection. Surgeons should be aware that chylopericardium is a rare but potential complication of lobectomy and SLND as it may help with early diagnosis, management, and prevention of cardiac tamponade.

Survival and morbidity in very preterm infants in Shenzhen: a multi-center study.

Objective: To analyze survival and morbidity among very preterm infants (VPIs) in Shenzhen and explore factors associated with survival without major morbidity. Methods: Between January 2022 and December 2022, 797 infants were admitted to 25 neonatal intensive care units in Shenzhen with gestational age (GA) < 32 weeks, excluded discharged against medical advice, insufficient information, and congenital malformation, 742 VPIs were included. Comparison of maternal and neonate characteristics, morbidities, survival, and survival without major morbidities between groups used Mann Whitney U test and X2 test, multivariate logistic regression was used to analyze of risk factors of survival without major morbidities. Results: The median GA was 29.86 weeks (interquartile range [IQR], 28.0-31.04), and the median birth weight was 1,250 g (IQR, 900-1,500). Of the 797 VPIs, 721 (90.46%) survived, 53.52% (38 of 71) at 25 weeks' or less GA, 86.78% (105 of 121) at 26 to 27 weeks' GA, 91.34% (211 of 230) at 28 to 29 weeks' GA, 97.86% (367 of 375) at 30 to 31 weeks' GA. The incidences of the major morbidities were moderate-to-severe bronchopulmonary dysplasia,16.52% (113 of 671); severe intraventricular hemorrhage and/or periventricular leukomalacia, 2.49% (17 of 671); severe necrotizing enterocolitis, 2.63% (18 of 671); sepsis, 2.34% (16 of 671); and severe retinopathy of prematurity, 4.55% (27 of 593), 65.79% (450 of 671) survived without major morbidities. After adjustment for GA, birth weight, and 5-min Apgar score, antenatal steroid administration (OR = 2.397), antenatal magnesium sulfate administration (OR = 1.554) were the positivity factors to survival without major morbidity of VPIs, however, surfactant therapy (OR = 0.684,), and delivery room resuscitation (OR = 0.626) that were the negativity factors. Conclusions: The present results indicate that survival and the incidence of survival without major morbidities increased with GA. Further, antenatal administration of steroids and magnesium sulfate, surfactant therapy, and delivery room resuscitation were pronounced determinants of survival without morbidities.

Comparisons of care practices for very preterm infants and their short-term outcomes in two tertiary centers in northwest and south China: A retrospective cohort study.

BACKGROUND: Care practices for very preterm infants and the mortality and morbidity of the infants vary widely among countries and regions with different levels of economic development, including the different areas in China. We aimed to compare the obstetric and delivery room practices of two representative tertiary newborn centers in the northwestern and southern regions of China and the mortality and morbidity of their very preterm infants. METHODS: A retrospective cohort study was conducted. Very preterm infants born between 220/7 and 316/7 weeks of gestation, and admitted to Qinghai Red Cross Hospital (QHH) and Shenzhen Baoan Women's and Children's Hospital (SZH) from January 1, 2018 to December 31, 2020, were included. The infants' characteristics and short-term outcomes, and the hospitals' care practices were compared between the two cohorts. RESULTS: Three hundred and two infants in QHH and 505 infants in SZH were enrolled, and the QHH cohort was more mature than the SZH cohort was (gestational age 30.14 (29.14-31.14) vs. 29.86 (27.86-31.00 weeks, respectively), p < 0.001). Fewer antenatal steroids and more tracheal intubations were used in QHH than in SZH [(73.8% vs. 90.9%, p < 0.001) and (68.2% vs. 35.0%, p < 0.001, respectively)]. The odds of mortality [aOR = 10.31, 95%CI: (6.04, 17.61)], mortality or major morbidity [aOR = 5.95, 95%CI: (4.05, 8.74)], mortality despite active treatment [aOR = 3.14, 95%CI: (1.31, 7.53)], mortality or major morbidity despite active treatment [aOR = 3.35, 95%CI: (2.17, 5.17)], moderate or severe bronchopulmonary dysplasia [aOR = 3.66, 95%CI: (2.20, 6.06)], and severe retinopathy of prematurity [aOR = 3.24, 95%CI: (1.19, 8.83)] were higher in the QHH cohort. No significant difference in the rate of severe neurological injury or necrotizing enterocolitis ≥ Stage 2 was found between the cohorts. CONCLUSION: Obstetric and delivery room care practices used in the management of very preterm infants differed considerably between the QHH and SZH cohorts. Very preterm infants born in QHH have higher odds of mortality or severe morbidity compared with those born in SZH.

Video-assisted thoracoscopic treatment as two-day surgery for lung neoplasms: a propensity-matched analysis.

BACKGROUND: Enhanced recovery after surgery programs have reduced complications and shortened hospital stays after lung resection. This study aimed to determine whether video-assisted thoracoscopic surgery performed as a two-day surgery for lung neoplasms was safe and cost-effective. METHODS: This retrospective, propensity-matched, cohort analysis was conducted from January 2020 to August 2020. Among 959 patients who underwent video-assisted thoracoscopic surgery, 739 underwent inpatient surgery and 220 underwent two-day surgery. Propensity-matched analysis, incorporating preoperative variables, was used to compare postoperative complications, post-discharge follow-up results, and hospitalization costs between the groups. RESULTS: Propensity matching estimated 218 patients in each group. The mean length of hospital stay was shorter in the two-day surgery group (2.17 ± 0.89 days) than in the inpatient surgery group (6.31 ± 2.13 days) (P < 0.001). Delayed removal of chest tubes accounted for over half of the delayed discharges in the inpatient (17 [54.8%]) and two-day surgery (13 [65.0%]) groups. The postoperative pneumonia/atelectasis incidence was lower in the two-day surgery group than in the inpatient surgery group (P = 0.032). The two-day surgery group patients were readmitted to the hospital due to massive pleural effusion, pneumothorax, fever, severe chest pain, and physical weakness. The mean total hospitalization cost in the two-day surgery group was lower than that in the inpatient surgery group (¥ 33,926.1 versus ¥ 38,422.7, P < 0.001). Basic medical, nursing, drug, laboratory-related, and nonsurgical consumable costs in the two-day surgery group were significantly reduced. CONCLUSIONS: Two-day surgery is a safe, feasible, and cost-effective procedure for selected patients with lung neoplasms when combined with accurate preoperative evaluations, successful intraoperative assessments, and effective postoperative health care guidance.

RNF4 controls the extent of replication fork reversal to preserve genome stability.

Replication fork reversal occurs via a two-step process that entails reversal initiation and reversal extension. DNA topoisomerase IIalpha (TOP2A) facilitates extensive fork reversal, on one hand through resolving the topological stress generated by the initial reversal, on the other hand via its role in recruiting the SUMO-targeted DNA translocase PICH to stalled forks in a manner that is dependent on its SUMOylation by the SUMO E3 ligase ZATT. However, how TOP2A activities at stalled forks are precisely regulated remains poorly understood. Here we show that, upon replication stress, the SUMO-targeted ubiquitin E3 ligase RNF4 accumulates at stalled forks and targets SUMOylated TOP2A for ubiquitination and degradation. Downregulation of RNF4 resulted in aberrant activation of the ZATT-TOP2A-PICH complex at stalled forks, which in turn led to excessive reversal and elevated frequencies of fork collapse. These results uncover a previously unidentified regulatory mechanism that regulates TOP2A activities at stalled forks and thus the extent of fork reversal.

Birth growth curves of neonates in high-altitude areas: A cross-sectional study.

Background: Since the current commonly used birth growth curves are unsuitable for neonates in high-altitude areas; this study aimed to establish birth growth curves for full-term neonates residing at 2,000-3,000 m. Methods: This cross-sectional study retrospectively analyzed the physical measurement data of 1,546 full-term neonates delivered at the Red Cross Hospital of Qinghai province, China, from July 2021 to April 2022. The percentile curves of birth weight, length, and head circumference of neonates of different gestational ages and genders were developed using curve fitting. The newly developed birth-weight percentile reference was compared with the INTERGROWTH-21st Neonatal Growth Curve (International Standard) and the Chinese Neonate Growth Curve (Chinese Standard). Results: The median birth weight, length, and head circumference of the study population were 3,200 g, 52.0 cm, and 32.8 cm, respectively, except for the group with a gestational age of 37 weeks. The growth indicators of male infants in all groups were higher than those of the female infants (P < 0.05). We found differences between the newly developed birth-weight percentile curves in the high-altitude areas and the International and Chinese Standards. Conclusion: Establishing birth growth curves corresponding to altitude may be more suitable than the existing standards for local medical staff to conduct health assessments of neonates.

Preoperative non-invasive visual localization of synchronous multiple lung cancers using three-dimensional computed tomography lung reconstruction.

BACKGROUND: Synchronous multiple primary lung cancers are becoming more common with increasing use of computed tomography for screening. Intraoperative localization and resection of ill-defined pulmonary ground-glass opacities during thoracoscopic resection is challenging. This study aimed to determine the clinical feasibility of non-invasive visual localization of these nodules by three-dimensional computed tomography lung reconstruction before sublobar resection. METHODS: Forty-four patients with synchronous multiple primary lung cancers underwent thoracoscopic pulmonary resection at our institution between June 2017 and August 2019. Preadmission computed tomography images were downloaded and reconstructed into a three-dimensional model. Small nodules (< 15 mm) were localized non-invasively by three-dimensional computed tomography lung reconstruction before surgery. Patient demographics, nodule characteristics, procedural details, pathological data, and outcomes were obtained from the medical records. RESULTS: One hundred and twenty-one pulmonary nodules from the 44 patients were scheduled for video-assisted thoracic surgery; 54 (44.6%) were pure ground-glass opacities and 57 (47.1%) were mixed ground-glass opacities. One hundred and seventeen nodules were localized preoperatively. The mean nodule diameter was 7.67 ± 3.87 mm. The mean distance from the nodule to the pleura was 14.84 ± 14.43 mm. All nodules were removed successfully by wedge resection (27 patients), lobectomy (26 patients), or segmentectomy (25 patients). Most lesions (85.1%) were malignant. Paraffin pathology revealed 12 cases of atypical adenomatous hyperplasia (9.92%), 13 of adenocarcinoma in situ (10.74%), 16 of minimally invasive adenocarcinoma (13.22%), and 73 of invasive adenocarcinoma (60.33%). CONCLUSIONS: Three-dimensional computed tomography lung reconstruction is a feasible and alternative method of visual localization for small lung nodules before sublobar resection in some suitable patients.

circ_0005962 functions as an oncogene to aggravate NSCLC progression.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading threat to human lives with high incidence and mortality. Circular RNAs were reported to play important roles in human cancers. The purpose of this study was to investigate the role of circ_0005962 and explore the underlying functional mechanisms. METHODS: The protein levels of Beclin 1, light chain3 (LC3-II/LC3-I), Pyruvate dehydrogenase kinase 4 (PDK4), Cleaved Caspase 3 (C-caspase 3), and proliferating cell nuclear antigen were examined using western blot analysis. Glycolysis was determined according to the levels of glucose consumption and lactate production. Xenograft model was constructed to investigate the role of circ_0005962 in vivo. RESULT: circ_0005962 expressed with a high level in NSCLC tissues and cells. circ_0005962 knockdown inhibited proliferation, autophagy, and glycolysis but promoted apoptosis in NSCLC cells. miR-382-5p was targeted by circ_0005962, and its inhibition reversed the role of circ_0005962 knockdown. Besides, PDK4, a target of miR-382-5p, was regulated by circ_0005962 through miR-382-5p, and its overexpression abolished the effects of miR-382-5p reintroduction. circ_0005962 knockdown suppressed tumor growth in vivo. CONCLUSION: circ_0005962 knockdown restrained cell proliferation, autophagy, and glycolysis but stimulated apoptosis through modulating the circ_0005962/miR-382-5p/PDK4 axis. Our study broadened the insights into understanding the mechanism of NSCLC progression.

Efficacy of budesonide in the prevention and treatment of bronchopulmonary dysplasia in premature infants and its effect on pulmonary function.

OBJECTIVE: This study was designed to explore the efficacy of budesonide (BUD) in preventing and treating bronchopulmonary dysplasia (BPD) in premature infants and its effect on pulmonary function. METHODS: A total of 94 premature infants with BPD who were born in our hospital were selected as the research subjects and divided into the control group (47 cases) for routine treatment and the research group (47 cases) for BUD therapy on the basis of routine treatment according to the random number table method. The incidence of BPD and the time of oxygen inhalation, ventilator ventilation, extubation and hospitalization were recorded in the two groups. In addition, arterial blood gas indexes (arterial oxygen saturation (SaO2), arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2)), inflammatory response indicators (interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor (TNF-α)), pulmonary function indexes (the ratio of time taken to reach peak expiratory flow to total expiratory time (TPTEF/TE), the ratio of peak expiratory volume to total expiratory volume (VPEF/VE), tidal expiratory flow at 25%/50%/75% remaining tidal volume (TEF25, TEF50, TEF75), and the incidence of complications were observed and compared. RESULTS: After treatment, SaO2 and PaO2 increased in both groups, and their values in the research group were higher than those in the control group; PaCO2 decreased in both groups, and the PaCO2 in the research group was lower than that in the control group (P<0.05). The post-treatment TNF-α, IL-6 and IL-8 levels decreased in both groups, and their levels in the research group were lower than those in the control group (all P<0.001). TPTEE/TE, VPEF/VE, TEF25, TEF50 and TEF75 increased in both groups after treatment, and their values in the research group were higher than those in the control group (all P<0.01). The research group required shorter oxygen inhalation time, ventilator ventilation time, time to extubation and hospitalization time than the control group (all P<0.001). The incidence of BPD and other complications in the research group were lower than that in the control group (8.51%, 6.38% vs. 23.40%, 21.28%; P=0.049, 0.036). CONCLUSION: BUD is effective in the prevention and treatment of BPD in premature infants, which can effectively reduce the incidence of BPD and other complications, improve blood gas indexes, reduce inflammatory reactions and promotes good pulmonary function in children.

Preoperative virtual simulation for synchronous multiple primary lung cancers using three-dimensional computed tomography lung reconstruction: a case report.

BACKGROUND: As the positions and sizes of nodules in synchronous multiple primary lung cancer (SMPLC) patients differ, the development of surgical strategies to maximize long-term survival and preserved postoperative pulmonary function in SMPLC patients for whom surgical resection is an alternative strategy presents challenges. CASE PRESENTATION: We provide a case managed through video-assisted thoracoscopic surgery (VATS) resection using three-dimensional computed tomography lung reconstruction (3D-CTLR) to reconstruct lobes containing pulmonary nodules to preoperatively simulate and intraoperatively guide the extent and method of resection. CONCLUSION: The successful attempt demonstrates a technically simplified, feasible alternative to preoperative plans utilizing less invasive VATS to manage SMPLC.

Adenylate kinase 1 deficiency disrupts mouse sperm motility under conditions of energy stress†.

Mammalian spermatozoa are highly polarized cells characterized by compartmentalized cellular structures and energy metabolism. Adenylate kinase (AK), which interconverts two ADP molecules into stoichiometric amounts of ATP and AMP, plays a critical role in buffering adenine nucleotides throughout the tail to support flagellar motility. Yet the role of the major AK isoform, AK1, is still not well characterized. Here, by using a proteomic analysis of testis biopsy samples, we found that AK1 levels were significantly decreased in nonobstructive azoospermia patients. This result was further verified by immunohistochemical staining of AK1 on a tissue microarray. AK1 was found to be expressed in post-meiotic round and elongated spermatids in mouse testis and subsequent mature sperm in the epididymis. We then generated Ak1 knockout mice, which showed that AK1 deficiency did not induce any defects in testis development, spermatogenesis, or sperm morphology and motility under physiological conditions. We further investigated detergent-modeled epididymal sperm and included individual or mixed adenine nucleotides to mimic energy stress. When only ADP was available, Ak1 disruption largely compromised sperm motility, manifested as a smaller beating amplitude and higher beating frequency, which resulted in less effective forward swimming. The energy restriction/recover experiments with intact sperm further addressed this finding. Besides, decreased AK activity was observed in sperm of a male fertility disorder mouse model induced by cadmium chloride. These results cumulatively demonstrate that AK1 was dispensable for testis development, spermatogenesis, or sperm motility under physiological conditions, but was required for sperm to maintain a constant adenylate energy charge to support sperm motility under conditions of energy stress.

Uniportal Video-Assisted Thoracoscopic Stapled Resection of Adult Diaphragmatic Eventration.

Surgery for an elevated diaphragm in adults is indicated only for patients with related severe dyspnea, orthopnea, or gastrointestinal problems. Experience in surgically treating eventration in adulthood is limited. Currently, diaphragmatic plication is the most frequently employed technique and should be attempted with minimally invasive approaches. Herein, we report 3 cases of diaphragmatic eventration managed through uniportal video-assisted thoracoscopic surgery stapled resection. These successful attempts provide a technically simple and feasible alternative for the management of diaphragmatic eventration.

Acetylation of XPF by TIP60 facilitates XPF-ERCC1 complex assembly and activation.

The XPF-ERCC1 heterodimer is a structure-specific endonuclease that is essential for nucleotide excision repair (NER) and interstrand crosslink (ICL) repair in mammalian cells. However, whether and how XPF binding to ERCC1 is regulated has not yet been established. Here, we show that TIP60, also known as KAT5, a haplo-insufficient tumor suppressor, directly acetylates XPF at Lys911 following UV irradiation or treatment with mitomycin C and that this acetylation is required for XPF-ERCC1 complex assembly and subsequent activation. Mechanistically, acetylation of XPF at Lys911 disrupts the Glu907-Lys911 salt bridge, thereby leading to exposure of a previously unidentified second binding site for ERCC1. Accordingly, loss of XPF acetylation impairs the damage-induced XPF-ERCC1 interaction, resulting in defects in both NER and ICL repair. Our results not only reveal a mechanism that regulates XPF-ERCC1 complex assembly and activation, but also provide important insight into the role of TIP60 in the maintenance of genome stability.

Association between Epstein-Barr virus and Thymic epithelial tumors: a systematic review.

The possible role of Epstein-Barr virus (EBV) in the pathogenesis of thymic epithelial tumors (TET) remains controversial. This study aimed to determine the prevalence of EBV in TET. We conducted a systematic review of relevant English-language studies published between January 1980 and December 2013. Effect size was calculated as event rates (95% confidence interval [CI]) by homogeneity testing using Cochran's Q and I2 statistics for benign TET, benign TET with myasthenia gravis (MG), and thymic carcinoma (TC). Among 136 potentially relevant studies, 22 met the inclusion criteria. Despite a considerable degree of heterogeneity, the pooled estimated incidences were 9% (95% CI, 1-23%), 20% (95% CI, 0-54%), and 6% (95% CI, 0-21%) for benign TET, benign TET with MG, and TC, respectively. There was significant heterogeneity among studies that used in situ hybridization (ISH) for both benign TET and benign TET with MG. According to the random-effects model, studies employing ISH yielded lower point estimates of EBV prevalence (5%) than those employing other methods (33%). Using the random-effects model, we found a lack of significant heterogeneity among studies from different geographic regions (p = 0.0848). Further, 12 of 23 lymphoepithelioma-like carcinoma (LELC) cases tested EBV-positive. The prevalence of EBV in benign TET with or without MG was lower than in nasopharyngeal carcinoma, suggesting that EBV plays a minor role in TET pathogenesis. Although the prevalence of EBV in TC was also low, EBV may play an important causal role in LELC. Further research is needed to clarify these associations.

Kink-type solutions of the SIdV equation and their properties.

We study the nonlinear integrable equation, u t + 2((u x u xx )/u) = ϵu xxx , which is invariant under scaling of dependent variable and was called the SIdV equation (see Sen et al. 2012 Commun. Nonlinear Sci. Numer. Simul. 17, 4115-4124 (doi:10.1016/j.cnsns.2012.03.001)). The order-n kink solution u [n] of the SIdV equation, which is associated with the n-soliton solution of the Korteweg-de Vries equation, is constructed by using the n-fold Darboux transformation (DT) from zero 'seed' solution. The kink-type solutions generated by the onefold, twofold and threefold DT are obtained analytically. The key features of these kink-type solutions are studied, namely their trajectories, phase shifts after collision and decomposition into separate single kink solitons.

Photogeneration of hydroxyl radical in Fe(III)-citrate-oxalate system for the degradation of fluconazole: mechanism and products.

The photochemical role of Fe(III)-citrate complex is significant in natural waters due to its ubiquitous existence and excellent photoreactivity at near neutral pH. Although there are many reports on the photoinduced degradation of pollutants in the Fe(III)-citrate system, the optimum pH for its photoreactivity is yet not clearly understood. Here, for the first time, we demonstrated that the optimum pH was 5.5 for the photoproduction of •OH in the Fe(III)-citrate system via kinetics modeling based on the steady-state approximation. According to the experimental results, the •OH photoproduction increased with increasing pH until 5.5 and then decreased in Fe(III)-citrate solution, which agreed well with the prediction trend of kinetic modeling. The effect of the common ligand oxalate on the photoreactivity of Fe(III)-citrate system was also investigated. The addition of oxalate promoted the photoproduction of •OH in Fe(III)-citrate solutions, and the measured [•OH]ss increased with oxalate concentration under a fixed Fe(III)-to-citrate ratio. Little synergistic effect exists in Fe(III)-citrate-oxalate system at pH 4.0-5.5. In contrast, an appreciable synergistic effect was observed at near neutral pH (6.0-8.0). Higher oxalate-to-citrate ratio facilitated the synergistic effect. Furthermore, antifungal drug fluconazole could be removed efficiently in the Fe(III)-citrate-oxalate system. The photodegradation kinetics also verified the optimum pH of Fe(III)-citrate system and synergistic effect of oxalate. By LC-ESI-MS/MS analyses, the photoproducts of fluconazole in the Fe(III)-citrate-oxalate system were identified and the reaction mechanism involving hydroxylation substitution and subsequent cleavage of heterocyclic amine was proposed. These findings suggest that Fe(III)-citrate exhibits best photoreactivity at pH 5.5, and the coexistence of reactive ligands will enhance its photoreactivity at circumneutral pH, indicating potential application in wastewater treatment via addition of appropriate citrate and co-ligands.