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Objective As the population ages and technology advances, lateral lumbar intervertebral fusion (LLIF) is gaining popularity for the treatment of degenerative lumbar scoliosis (DLS). This study investigated the feasibility, minimally invasive concept, and benefits of LLIF for the treatment of DLS by observing and assessing the clinical efficacy, imaging changes, and complications following the procedure. Methods A retrospective analysis was performed for 52 DLS patients (12 men and 40 women, aged 65.84 ± 9.873 years) who underwent LLIF from January 2019 to January 2023. The operation time, blood loss, complications, clinical efficacy indicators (visual analogue scale [VAS], Oswestry disability index [ODI], and 36‐Item Short Form Survey), and imaging indicators (coronal position: Cobb angle and center sacral vertical line–C7 plumbline [CSVL–C7PL]; and sagittal position: sagittal vertical axis [SVA], lumbar lordosis [LL], pelvic incidence angle [PI], and thoracic kyphosis angle [TK] were measured). All patients were followed up. The above clinical evaluation indexes and imaging outcomes of patients postoperatively and at last follow‐up were compared to their preoperative results. Results Compared to the preoperative values, the Cobb angle and LL angle were significantly improved after surgery (p 0.05) but improved significantly at follow‐up (p 0.05) but considerably improved during follow‐up (p

Abstract Background and objective Cancer ratio (CR), which is defined as serum lactate dehydrogenase (LDH) to pleural fluid adenosine deaminase (ADA) ratio, has been reported to be a useful diagnostic marker for malignant pleural effusion (MPE). Whether its diagnostic accuracy is affected by age remains unknown. This study aimed to investigate the effects of age on the diagnostic accuracy of CR. Methods The participants in this study were from a prospective cohort (SIMPLE cohort, n = 199) and a retrospective cohort (BUFF cohort, n = 158). All participants were patients with undiagnosed pleural effusion (PE). We used receiver operating characteristic (ROC) curves to evaluate the diagnostic accuracy of CR. The effect of age on the diagnostic accuracy of CR was investigated by adjusting the upper limit of age for participant enrolment. Results Eighty-eight MPE patients were verified in the SIMPLE cohort, and thirty-five MPE patients were verified in the BUFF cohort. The AUCs of CR in the SIMPLE and BUFF cohorts were 0.60 (95% CI: 0.52–0.68) and 0.63 (95% CI: 0.54–0.71), respectively. In both cohorts, the AUCs of CR decreased with the advancement of age. Conclusion Age can affect the diagnostic accuracy of CR for MPE. CR has limited diagnostic value in older patients. Key message Cancer ratio is a promising diagnostic marker for malignant pleural effusion. This study revealed that its diagnostic accuracy decreased in older patients. Its diagnostic accuracy is overestimated by previous studies using tuberculosis and pneumonia patients as controls.

Background: Our objective was to assess the viability and oncological security of a gasless, transaxillary single-incision endoscopic procedure for performing total thyroidectomy and bilateral central neck dissection (TT + BCND). This study focused on patients diagnosed with bilateral papillary thyroid microcarcinoma (PTMC). Method: Between April 2020 and November 2021, 22 patients with bilateral PTMC underwent single-incision, gasless, transaxillary endoscopic TT + BCND. The patients’ clinicopathologic characteristics, surgical completeness and complications were analyzed. Result: Single-incision, gasless, transaxillary endoscopic TT + BCND was successful performed in all patients. The median (IQR) total surgical time was 143 (85–160) min. Only two patients experienced transient unilateral RLN palsy or transient hypocalcemia. All these complications resolved within 1 month after surgery. The median duration of hospital stay after surgery was 4 (3–4.5) days. The median hospitalization expense for these patients was 3848 (3781–4145) USD. The median number of lymph node yielded was 10.5 (8–15). The cosmetic outcomes were well-received by all individuals. Conclusion: In certain cases, gasless, transaxillary endoscopic TT + BCND procedure performed through a single incision proved to be a secure alternative for managing bilateral PTMC.

ABSTRACTGraphdiyne (GDY) is an emerging two-dimensional carbon allotrope featuring a direct bandgap and fascinating physical and chemical properties, and it has demonstrated its promising potential in applications of catalysis, energy conversion and storage, electrical/optoelectronic devices, etc. In particular, the recent breakthrough in the synthesis of large-area, high-quality and ultrathin GDY films provides a feasible approach to developing high-performance electrical devices based on GDY. Recently, various GDY-based electrical and optoelectronic devices including multibit optoelectronic memories, ultrafast nonvolatile memories, artificial synapses and memristors have been proposed, in which GDY plays a crucial role. It is essential to summarize the recent breakthrough of GDY in device applications as a guidance, especially considering that the existing GDY-related reviews mainly focus on the applications in catalysis and energy-related fields. Herein, we review GDY-based novel memory and neuromorphic devices and their applications in neuromorphic computing and artificial visual systems. This review will provide an insight into the design and preparation of GDY-based devices and broaden the application fields of GDY.

Pediatric acute hyperextension spinal cord injury (SCI) named as PAHSCI by us, is a special type of thoracolumbar SCI without radiographic abnormality and highly related to back-bend in dance training, which has been increasingly reported. At present, it has become the leading cause of SCI in children, and brings a heavy social and economic burden. Both domestic and foreign academic institutions and dance education organizations lack a correct understanding of PAHSCI and relevant standards, specifications or guidelines. In order to provide standardized guidance, the expert team formulated this guideline based on the principles of science and practicability, starting from the diagnosis, differential diagnosis, etiology, admission evaluation, treatment, complications and prevention. This guideline puts forward 23 recommendations for 14 related issues.

Abstract Background The response of advanced clear cell renal cell carcinoma (ccRCC) to immunotherapy is still not durable, suggesting that the immune landscape of ccRCC still needs to be refined, especially as some molecules that have synergistic effects with immune checkpoint genes need to be explored. Methods The expression levels of CENPM and its relationship with clinicopathological features were explored using the ccRCC dataset from TCGA and GEO databases. Quantitative polymerase chain reaction (qPCR) analysis was performed to validate the expression of CENPM in renal cancer cell lines. Kaplan-Meier analysis, COX regression analysis and Nomogram construction were used to systematically evaluate the prognostic potential of CENPM in ccRCC. Besides, single gene correlation analysis, protein–protein interaction (PPI) network, genetic ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) were used to predict the biological behaviour of CENPM and the possible signalling pathways involved. Finally, a comprehensive analysis of the crosstalk between CENPM and immune features in the tumor microenvironment was performed based on the ssGSEA algorithm, the tumor immune dysfunction and exclusion (TIDE) algorithm, the TIMER2.0 database and the TISIDB database. Results CENPM was significantly upregulated in ccRCC tissues and renal cancer cell lines and was closely associated with poor clinicopathological features and prognosis. Pathway enrichment analysis revealed that CENPM may be involved in the regulation of the cell cycle in ccRCC and may have some crosstalk with the immune microenvironment in tumors. The ssGSEA algorithm, CIBERSOPT algorithm suggests that CENPM is associated with suppressor immune cells in ccRCC such as regulatory T cells. The ssGSEA algorithm, CIBERSOPT algorithm suggests that CENPM is associated with suppressor immune cells in ccRCC such as regulatory T cells. Furthermore, the TISIDB database provides evidence that not only CENPM is positively associated with immune checkpoint genes such as CTLA4, PDCD1, LAG3, TIGIT, but also chemokines and receptors (such as CCL5, CXCL13, CXCR3, CXCR5) may be responsible for the malignant phenotype of CENPM in ccRCC. Meanwhile, predictions based on the TIDE algorithm support that patients with high CENPM expression have a worse response to immunotherapy. Conclusions The upregulation of CENPM in ccRCC predicts a poor clinical outcome, and this malignant phenotype may be associated with its exacerbation of the immunosuppressive state in the tumor microenvironment.

Objective: To report a case of macular injury caused by short-term exposure to a handheld high-intensity light emitting diode (LED) light. Design: Interventional case report. Participant: A patient with macular injury caused by short-term exposure to the light of a handheld high-intensity LED device. Intervention: The patient was examined and followed for 3 months after exposure with ophthalmologic examinations (including funduscopy, optical coherence tomography [OCT], fluorescein angiography [FA], and multifocal electroretinography [mfERG]). The injured eye was treated with one retrobulbar injection of 20 mg triamcinolone acetonide at 5 days after exposure. Main outcome measures: Visual acuity, ophthalmoscopic, and OCT findings. Results: 3 days after exposure, the best corrected visual acuity (BCVA) of the right eye was 6/20. OCT revealed the acute stage of the injury with eminence of the retinal pigment epithelium (RPE). BCVA was improved to 16/20 and 20/20 at 19 and 33 days after exposure, respectively. OCT results of follow-ups at five days, 19 days, 33 days and 3 months after exposure have demonstrated the restoration process of the injury. Conclusions: Short-term exposure to high-intensity LED light may cause damage to the retina. As the expansion of LED use in modern life, education and supervision are of urgent need for public health.

Abstract Background Mindfulness-based cognitive therapy (MBCT) is a promising alternative treatment for generalized anxiety disorder (GAD). The objective of this study was to examine whether the efficacy of group MBCT adapted for treating GAD (MBCT-A) was noninferior to group cognitive behavioural therapy (CBT) designed to treat GAD (CBT-A), which was considered one of first-line treatments for GAD patients. We also explored the efficacy of MBCT-A in symptomatic GAD patients compared with CBT-A for a variety of outcomes of anxiety symptoms, as well as depressive symptoms, overall illness severity, quality of life and mindfulness. Methods This was a randomized, controlled, noninferiority trial with two arms involving symptomatic GAD patients. Adult patients with GAD (n = 138) were randomized to MBCT-A or CBT-A in addition to treatment as usual (TAU). The primary outcome was the anxiety response rate assessed at 8 weeks after treatment as measured using the Hamilton Anxiety Scale (HAMA). Secondary outcomes included anxiety remission rates, scores on the HAMA, the state-trait anxiety inventory (STAI), the Hamilton Depression Scale (HAMD), the Severity Subscale of the Clinical Global Impression Scale (CGI-S), and the 12-item Short-Form Health Survey (SF-12), as well as mindfulness, which was measured by the Five Facet Mindfulness Questionnaire (FFMQ). Assessments were performed at baseline, 8 weeks after treatment, and 3 months after treatment. Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed for primary analyses. The χ2 test and separate two-way mixed ANOVAs were used for the secondary analyses. Results ITT and PP analyses showed noninferiority of MBCT-A compared with CBT-A for response rate [ITT rate difference = 7.25% (95% CI: -8.16, 22.65); PP rate difference = 5.85% (95% CI: − 7.83, 19.53)]. The anxiety remission rate, overall illness severity and mindfulness were significantly different between the two groups at 8 weeks. There were no significant differences between the two groups at the 3-month follow-up. No severe adverse events were identified. Conclusions Our data indicate that MBCT-A was noninferior to CBT-A in reducing anxiety symptoms in GAD patients. Both interventions appeared to be effective for long-term benefits. Trial registration Registered at chictr.org.cn (registration number: ChiCTR1800019150 , registration date: 27/10/2018).

BackgroundEndoscopic thyroidectomy (ET) via gasless unilateral axillary (GUA) approach has been widely implemented worldwide. Based on our concept of mesothyroid excision in open surgery, we proposed a novel anatomy-based five-settlement method in ET via the GUA approach. This preliminary report aimed to explore the efficacy and safety of this method in patients with papillary thyroid carcinoma (PTC).MethodsPTC patients who underwent endoscopic ET and unilateral central compartment neck dissection (CCND) via GUA approach with the five-settlement method at the Department of General Surgery, Nanfang Hospital, Southern Medical University from March 2020 to December 2021 were retrospectively collected. The data included general clinicopathological characteristics, surgical information (including duration, complication, and clinicopathological features), and hospital stay information, and other medical records were documented.ResultsIn total, 521 patients underwent lobectomy and CCND under the GUA approach with the five-settlement method. The mean number of lymph nodes yielded (LNY) and positive lymph nodes (PLN) was 5.7 ± 4.3 (range, 1–30) and 1.0 ± 1.8 (range, 0–12), respectively. The incidence of transient recurrent laryngeal nerve injury was 1.1%. Chyle leakage and Horner’s syndrome respectively occurred in one patient (0.2%). Five (0.9%) patients developed a hematoma. No severe complications or conversion to open surgery have occurred.ConclusionThe five-settlement method could be implemented safely and efficiently in ET+CCND via the GUA approach in selected PTC patients.

Abstract Background Patients who do not respond to conservative treatment of the isthmus are often treated with surgery. We used direct repair plus intersegment pedicle screw fixation for the treatment of lumbar spondylolysis. The aim of this observational study was to assess the effects of this technique and evaluate various risk factors potentially predicting the probability of disc and facet joint degeneration after instrumentation. Methods The study included 54 male L5 spondylolysis patients who underwent pars repair and intersegment fixation using pedicle screws. Bony union was evaluated using reconstruction images of computed tomography. Radiographic changes, including disc height, vertebral slip, facet joint and disc degeneration in the grade of adjacent and fixed segments, were determined from before to final follow-up. Logistic regression analysis was performed to identify factors associated with the incidence of disc and facet joint degeneration. Results Bony union was achieved in all cases. Logistic regression analysis revealed that instrumentation durations of greater than 15.5 months and 21.0 months were significant risk factors for the incidence of L4/5 and L5S1 facet degeneration, respectively. Conclusions Intersegmental pedicle screw fixation provides good surgical outcomes and good isthmic bony union rates in patients with lumbar spondylolysis. The duration of fixation was confirmed as a risk factor for facet joint degeneration. Once bony union is achieved, instrument removal should be recommended.

Abstract Background Despite the continuous development and evolution of surgical methods and techniques, proximal hypospadias remains one of the most challenging issues for pediatric urologists. This study aims to evaluate the indications and postoperative complications of our new modified Duckett urethroplasty. Methods A total of 133 patients with proximal hypospadias who underwent repair of the modified Duckett urethroplasty from February 2016 to February 2021 were reviewed. The median age of patients was 3 years (range 1–16). All patients had severe chordee. One senior experienced pediatric urologist performed all the surgeries. Catheter was removed 14 days after the surgery. Results The location of the urethral meatus was proximal penile in 26 patients (19.5%), penoscrotal in 60 (45.1%), scrotal in 31 (23.3%), and perineal in 16 (12.0%). The mean length of the urethral defect was 4.5 cm (range 2.5–10). The median duration of follow-up was 46 months (range 8–67). Complications occurred in 31 patients (23.3%), including urethra-cutaneous fistula in 22 (16.5%), urethral stenosis in 7 (5.3%), and urethral diverticulum in 2 (1.5%). No recurrent chordee were found in all cases. All patients who developed complications were treated successfully at our hospital. Conclusions Our modified Duckett urethroplasty showed functionally and cosmetically favorable outcomes, with a lower incidence of postoperative complications. To the best of our knowledge, the novel Duckett technique is a feasible and suitable option for patients who suffer from proximal hypospadias with severe chordee and dysplasia of the urethral plate.

BackgroundInconsistent relationships have been shown between cigarette smoking and hypospadias in offspring. The purpose of this study was to summarize epidemiological evidence to evaluate the relationship between parental smoking and the risk of hypospadias.MethodsUp until October 2022, PubMed, EMBASE, Web of Science, and the Cochrane Library were systematically searched for qualified research. The summary RRs and 95% CIs were calculated using either a fixed-effects or a random-effects model. There were subgroup analyses undertaken to identify potential sources of heterogeneity.Results44 studies with 16,637,830 participants were included in our meta-analysis. Overall, maternal active smoking [risk ratio (RR) = 0.94; 95% confidence interval (CI): 0.90–0.99; P

Abstract Artificial synapses and neurons are crucial milestones for neuromorphic computing hardware, and memristors with resistive and threshold switching characteristics are regarded as the most promising candidates for the construction of hardware neural networks. However, most of the memristors can only operate in one mode, that is, resistive switching or threshold switching, and distinct memristors are required to construct fully memristive neuromorphic computing hardware, making it more complex for the fabrication and integration of the hardware. Herein, we propose a flexible dual‐mode memristor array based on core–shell CsPbBr3@graphdiyne nanocrystals, which features a 100% transition yield, small cycle‐to‐cycle and device‐to‐device variability, excellent flexibility, and environmental stability. Based on this dual‐mode memristor, homo‐material‐based fully memristive neuromorphic computing hardware—a power‐free artificial nociceptive signal processing system and a spiking neural network—are constructed for the first time. Our dual‐mode memristors greatly simplify the fabrication and integration of fully memristive neuromorphic systems.

BackgroundInvestigations regarding the association between maternal smoking and specific urogenital teratogenesis exist. However, an integrated systematic review and meta-analysis studying the relationship by encompassing the whole urogenital system is essential.ObjectiveEven though many studies about inborn urogenital malformations have been conducted, its etiologic factors and exact pathogenesis are still unclear. Our aim is to assess the risk of congenital urogenital malformations in offspring of smoking pregnant women.ResultsThe meta-analysis, covering 41 case-control and 11 cohort studies, suggested that maternal smoking was associated with an increased risk of urogenital teratogenesis (odds ratio [OR] = 1.13, 95% confidence interval [CI]: 1.04–1.23, p = 0.005), cryptorchidism (OR = 1.18, 95%CI: 1.12-1.24, p = 0.0001), hypospadias (OR = 1.16, 95%CI: 1.01-1.33, p = 0.039), and kidney malformations (OR = 1.30, 95%CI: 1.14-1.48, p = 0.0001). Moreover, paternal smoking during the mother’s pregnancy was also significantly associated (OR = 1.26, 95%CI: 1.03-1.55, p = 0.028). The association between smoking > 10 cigarettes/day was evident but was not significant (OR = 1.24, 95%CI:0.81-1.88, p = 0.323).ConclusionOur results showed that maternal smoking during pregnancy increased the risk of congenital urogenital malformations. In numerous epidemiological studies, maternal smoking during pregnancy has a significant role in fetal development. Therefore, quitting tobacco use may be an effective method for reducing the risk of congenital urogenital malformation in pregnant women.

Numerous temperate plants and animals on the Qinghai-Tibet Plateau (QTP) are hypothesized to have differentiated due to vicariant allopatric speciation associated with the geologic uplifts. However, this hypothesis has rarely been tested through a phylogeographic study of relative species in a broader geographic context, including the QTP, Tianshan Mountains, Mongolian Plateau, and surrounding regions. To understand the speciation and diversification process of plants across this wide area, phylogeographic analysis were examined from Scrophularia incisa and two other closely relative species comprising S. kiriloviana and S. dentata. Thirty-two populations of the three close relatives were genotyped using chloroplast DNA fragments and nuclear microsatellite loci to assess population structure and diversity, supplemented by phylogenetic dating, ancestral area reconstructions and species distribution modelings, as well as niche identity tests. Our chloroplast DNA (cpDNA) phylogeny showed that this monophyletic group of desert and steppe semi-shrub is derived from a Middle Pliocene ancestor of the Central Asia. Lineages in Central Asia vs. China diverged through climate/tectonic-induced vicariance during Middle Pliocene. Genetic and ENM data in conjunction with niche differentiation analyses support that the divergence of S. incisa, S. dentata and S. kiriloviana in China lineage proceeded through allopatric speciation, might triggered by early Pleistocene climate change of increase of aridification and enlargement of deserts, while subsequent climate-induced cycles of range contractions/expansions enhanced the geographical isolation and habit fragmentation of these taxa. These findings highlight the importance of the Plio-Pleistocene climate change in shaping genetic diversity and driving speciation in temperate steppes and deserts of Northwestern China.

Abstract Background When symptomatic spondylolysis fail to respond to nonoperative treatment, surgical management may be required. A number of techniques have been described for repair by intrasegmental fixation with good results; however, there are still some problems. We reported a repair technique with temporary intersegmental pedicle screw fixation and autogenous iliac crest graft. The aim of present study is to assess the clinical outcomes of L5 symptomatic spondylolysis with this technique. Methods A retrospective analysis of 128 patients with L5 spondylolysis treated with this method was performed. According to CT scan, the spondylolysis were classified into 3 categories: line, intermediate, and sclerosis type. The diagnostic block test of L5 bilateral pars defect was done in all patients preoperatively. The sagittal and axial CT images were used to determine the bone union. The healing time, complications, number of spina bifida occulta, Japanese Orthopedic Association (JOA) score, and VAS for back pain were recorded. After fixation removal, the rate of ROM preservation at L5S1 was calculated. Results There were 97 patients (194 pars) followed with mean follow-up of 23 months (range, 12–36 months). The union rate of pars was 82.0% at 12 months and 94.3% at 24 months postoperatively. Low back pain VAS significantly (P < 0.05) improved from preoperative mean value of 7.2 to 1.3 at the final follow-up postoperatively (P < 0.05). JOA score increased significantly postoperatively (P < 0.05) with average improvement rate of 79.3%. The rates of L5S1 ROM preservation were 79.8% and 64.0% after fixation removal at 1 and 2 years postoperatively. There were 3 patients of delayed incision healing without other complications. Conclusions Although sacrificing L5S1 segment motion temporarily, more stability was obtained with intersegmental fixation. This technique is reliable for spondylolysis repair which has satisfactory symptom relief, high healing rate, low incidence of complications, and preserve a large part of ROM for fixed segment.

Abstract Background Several studies demonstrate that endoplasmic reticulum (ER) stress-mediated epithelial-mesenchymal transition (EMT) is involved in the process of bleomycin (BLM)-induced pulmonary fibrosis. Tauroursodeoxycholic acid (TUDCA), a bile acid with chaperone properties, is an inhibitor of ER stress. This study aimed to investigate the preventive effects of TUDCA on BLM-induced EMT and lung fibrosis. Methods The model of lung fibrosis was established by intratracheal injection with a single dose of BLM (3.0 mg/kg). In TUDCA + BLM group, mice were intraperitoneally injected with TUDCA (250 mg/kg) daily. Results BLM-induced alveolar septal destruction and inflammatory cell infiltration were alleviated by TUDCA. BLM-induced interstitial collagen deposition, as determined by Sirius Red staining, was attenuated by TUDCA. BLM-induced elevation of pulmonary α-smooth muscle actin (α-SMA) and reduction of pulmonary E-cadherin were attenuated by TUDCA. BLM-induced pulmonary Smad2/3 phosphorylation was suppressed by TUDCA. BLM-induced elevation of Ki67 and PCNA was inhibited by TUDCA in mice lungs. In addition, BLM-induced elevation of HO-1 (heme oxygenase-1) and 3-NT (3-nitrotyrosine) was alleviated by TUDCA. Finally, BLM-induced upregulation of pulmonary GRP78 and CHOP was attenuated by TUDCA. Conclusions These results provide evidence that TUDCA pretreatment inhibits Smad2/3-medited EMT and subsequent lung fibrosis partially through suppressing BLM-induced ER stress and oxidative stress.

We aimed to explore the associations between the age at which children undergo surgery for hypospadias and a range of social and clinical factors in a single center. Our aim was to promote the early surgical treatment of children with hypospadias. For a 6-year period, social and clinical data were collected from all children undergoing surgery to repair hypospadias in Children's Hospital of Chongqing Medical University (Chongqing, China), located in southwest of China. We analyzed the correlations between age at surgery and a range of social and clinical factors. A total of 1611 eligible cases were recruited, with a mean age of 54.3 months and a median age of 42 months: 234 cases (14.5%) were classified into a “timely operation” group, 419 (26.0%) cases into a “subtimely operation” group, and 958 (59.5%) cases into a “delayed operation” group. According to multivariate regression analyses, the higher the regional economic level, the closer the urethral opening to the perineum, and the higher the educational level of the guardians was, the younger the children were when they underwent the initial surgery for hypospadias; this was also the case for families without other children. Our subgroup analysis showed that the primary educational level of the guardians was a risk factor for subtimely surgery in their children (odds ratio [OR] = 1.52, 95% confidence interval [CI]: 1.08–2.15, P < 0.05). A lower regional economic level (OR = 1.87, 95% CI: 1.26–2.78, P < 0.01), a lower educational level of the guardians (OR = 3.84, 95% CI: 2.31–6.41, P < 0.01), and an anterior-segment urethral opening (OR1 [vs middle hypospadias] = 2.07, 95% CI: 1.42–3.03; OR2 [vs posterior hypospadias] = 2.63, 95% CI: 1.75–3.95; P < 0.01) were all risk factors for delayed surgery in children.

Several studies found that reduction of 5-hydroxymethylcytosine (5hmC), a marker of DNA hydroxymethylation highly enriched in developing brain, is associated with anxiety-like behaviors. This study aimed to investigate whether gestational arsenic (As) exposure induces anxiety-like behaviors in adult offspring by reducing DNA hydroxymethylation in the developing brain. The dams drank ultrapure water containing NaAsO2 (15 mg/L) throughout pregnancy. Anxiety-like behaviors were evaluated and developing brain 5hmC was detected. Results showed that anxiety-like behaviors were observed in As-exposed adult offspring. In addition, 5hmC content was reduced in As-exposed fetal brain. Despite no difference on Tet1, Tet2 and Tet3 expression, TET activity was suppressed in As-exposed fetal brain. Mechanistically, alpha-ketoglutarate (α-KG), a cofactor for TET dioxygenases, was reduced and Idh2, a key enzymatic gene for mitochondrial α-KG synthesis, was downregulated in As-exposed fetal brain. Of interest, ascorbic acid, a cofactor for TET dioxygenases, reversed As-induced suppression of TET activity. Moreover, ascorbic acid attenuated As-induced reduction of 5hmC in fetal brain. In addition, ascorbic acid alleviated As-induced anxiety-like behaviors in adult offspring. Taken together, these results suggest that gestational As exposure induces anxiety-like behaviors in adult offspring, possibly at part, by inhibiting DNA hydroxymethylation in developing brain.

Owing to the complexity of the climate system and limitations of numerical dynamical models, machine learning based on big data has been used for climate forecasting in recent years. In this study, we attempted to use an artificial neural network (ANN) for summer precipitation forecasts in the Yangtze-Huaihe River Basin (YHRB), eastern China. The major ANN employed here is the standard backpropagation neural network (BPNN), which was modified for application to the YHRB. Using the analysis data of precipitation and the predictors/factors of atmospheric circulation and sea surface temperature, we calculated the correlation coefficients between precipitation and the factors. In addition, we sorted the top six factors for precipitation forecasts. In order to obtain accurate forecasts, month (factor)-to-month (precipitation) forecast models were applied over the training and validation periods (i.e., summer months over 1979–2011 and 2012–2019, respectively). We compared the standard BPNN with the BPNN using a genetic algorithm-based backpropagation (GABP), support vector machine (SVM) and multiple linear regression (MLR) for the summer precipitation forecast after the model training period, and found that the GABP method is the best among the above methods for precipitation forecasting, with a mean absolute percentage error (MAPE) of approximately 20% for the YHRB, which is substantially lower than the BPNN, SVM and MLR values. We then selected the best summer precipitation forecast of the GABP month-to-month models by summing up monthly precipitation, in order to obtain the summer scale forecast, which presents a very successful performance in terms of evaluation measures. For example, the basin-averaged MAPE and anomaly rate reach 4.7% and 88.3%, respectively, for the YHRB, which can be a good recommendation for future operational services. It appears that sea surface temperatures (SST) in some key areas dominate the factors for the forecasts. These results indicate the potential of applying GABP to summer precipitation forecasts in the YHRB.

Red sage (Salvia miltiorrhiza) is a widely used medicinal plant for treatment of cardiovascular and cerebrovascular diseases. Because of excessive excavation by huge market demand and habitat loss by human activities, the wild population resources of S. miltiorrhiza have reduced drastically in recent years. Meanwhile, population status of two closely related species S. bowleyana and S. paramiltiorrhiza were in a trend of decreasing due to their potential replacement of S. miltiorrhiza. Particularly, S. paramiltiorrhiza was threatened and endemic to a small region in eastern China. However, to date there has been no conservation genetic research reported for wild S. miltiorrhiza population and its endangered relatives. Assess the wild germplasm diversity for S. miltiorrhiza and its related species would provide fundamental genetic background for cultivation and molecular breeding of this medicinally important species. In the present study, we investigated the genetic diversity, population structure, and intra/inter-specific differentiation of S. miltiorrhiza and above two relatives using 2b-RAD genome-wide genotyping method. By investigating 81 individuals of S. miltiorrhiza, 55 individuals of S. bowleyana and 15 individuals of S. paramiltiorrhiza from 23 locations in China, we obtained 23,928 SNPs in total. A comparatively high genetic diversity was observed in S. miltiorrhiza (π = 0.0788, He = 0.0783 ± 0.0007). The observed and expected heterozygosity in populations of these three species ranged from 0.0297 to 0.1481 and 0.0251 to 0.831, respectively. Two major lineage groups were detected in the examined S. miltiorrhiza populations. The results indicated that Dabie Mountain as a genetic diversity center of S. miltiorrhiza and possible complex inter-specific genetic exchange/hybridization occurred between S. miltiorrhiza and the two relatives. We suggest that strategic conservation and germplasm preservation should be considered not only for wild populations of S. miltiorrhiza, but also for its related S. bowleyana and S. paramiltiorrhiza.

Several epidemiological studies reported that chronic arsenic exposure increased risk of prostate cancer. This study aimed to investigate whether chronic NaAsO2 exposure elevates stemness and chemoresistance in prostate cancer cells. DU145 (wild-type p53) and PC-3 (p53-null) cells were exposed to NaAsO2 (2 μmol/L) for 30 generations. IC50s to docetaxel and cisplatin were increased in NaAsO2-exposed DU145 and PC-3 cells. The number of tumor spheres was elevated in NaAsO2-exposed DU145 and PC-3 cells. Nanog, SOX-2 and ALDH1A1, three markers of cancer stemness, were upregulated in NaAsO2-exposed PC-3 spheres. Moreover, NaAsO2-exposed DU145 and PC-3 cells were arrested in G2/M phase. Histone H2AX phosphorylation on Ser139, an indicator for DNA double-strand break, was upregulated in NaAsO2-exposed DU145 and PC-3 cells. ATM phosphorylation on Ser1981, a key sensor of genotoxic stress, was rapidly elevated in NaAsO2-exposed DU145 cells. Phosphor-p53, a downstream molecule of ATM signaling, and p21, a direct target of p53, were upregulated in NaAsO2-exposed DU145 cells. Unexpectedly, p21 was also elevated in NaAsO2-exposed p53-null PC-3 cells. Antioxidant NAC alleviated NaAsO2-induced ATM phosphorylation, cell cycle arrest, and subsequent stemness enhancement and chemoresistance in both DU145 and PC-3 cells. These results suggest that ROS-mediated genotoxic stress is involved in NaAsO2-induced cell cycle arrest, stemness enhancement and chemoresistance of prostate cancer cells in a p53-independent manner.

In our previous study, we have shown that CRLF1 can promote proliferation and metastasis of papillary thyroid carcinoma (PTC); however, the mechanism is unclear. Herein, we investigated whether the interaction of CRLF1 and MYH9 regulates proliferation and metastasis of PTC cells via the ERK/ETV4 axis. Immunohistochemistry (IHC), qPCR, and Western blotting assays were performed on PTC cells and normal thyroid cells to profile specific target genes. In vitro assays and in vivo assays were also conducted to examine the molecular mechanism. Results showed that CRLF1 directly bound MYH9 to enhance the stability of CRLF1 protein. Inhibition of MYH9 in PTC cells overexpressing CRLF1 significantly reversed malignant phenotypes, and CRLF1 overexpression activated ERK pathway, in vitro, and in vivo. RNA-sequencing revealed that ETV4 is a downstream target gene of CRLF1, which was up-regulated following ERK activation. Moreover, it was revealed that ETV4 is highly expressed in PTC tissues and is associated with poor prognosis. Finally, the ChIP assays showed that ETV4 induces the expression of matrix metalloproteinase 1 (MMP1) by binding to its promoter on PTC cells. Altogether, our study demonstrates that CRLF1 interacts with MYH9, promoting cell proliferation and metastasis via the ERK/ETV4 axis in PTC.

Background: Many clinical studies over the past decade have indicated positive outcomes for patients treated with Dynesys dynamic stabilization for lumbar degenerative disease. However, long-term outcomes of Dynesys for lumbar spinal stenosis are rarely reported. The aim of this study was to analyze the long-term clinical and radiologic outcomes for patients with lumbar spinal stenosis treated with Dynesys stabilization. Methods: Thirty-eight patients with lumbar spinal stenosis were treated with Dynesys stabilization from July 2008 to March 2010. The minimal duration of follow-up was 72 months. The patients were divided into stenosis and spondylolisthesis groups according to degenerative spondylolisthesis. Clinical outcomes were evaluated using the Oswestry Disability Index (ODI) and visual analog scale (VAS). Radiographic evaluations included range of motion (ROM) and the disc heights of stabilized segments and the upper adjacent segments. We also evaluated the occurrence of radiographic and symptomatic adjacent segment degeneration (ASD). Results: There were 23 patients in stenosis group and 15 patients in spondylolisthesis group. The ODI scores were significantly improved at the final follow-up evaluation, as compared to the baseline values (16.1 ± 5.7 vs. 57. 2 ± 14.2, t = 61.41, P < 0.01). The VAS scores for back and leg pain were significantly improved from 4.82 ± 0.89 and 4.04 ± 0.82 preoperatively to 0.93 ± 0.61 and 0.54 ± 0.51 postoperatively (t = 6.59, P < 0.01, and t = 5.91, P < 0.01, respectively). There were no differences between the two groups with respect to VAS and ODI scores. The ROM of stabilized segments decreased significantly from 7.8° ± 2.4° to 4.5° ± 1.5° (t = 7.18, P < 0.05), while the upper adjacent segments increased significantly from 8.3° ± 2.4° to 10.4° ± 2.4° (t = 2.87, P = 0.01). The change in disc height of stabilized segments was not significant (11.9 ± 2.1 preoperatively vs. 12.5 ± 1.5 postoperatively, t = 1.43, P = 0.15), whereas the decrease in disc height of the upper adjacent segments was significant (12.5 ± 2.0 preoperatively vs. 11.0 ± 1.7 postoperatively, t = 2.94, P = 0.01). The occurrence of radiographic and symptomatic ASD was 16% (6/38) and 3% (1/38), respectively. Conclusions: Decompression and Dynesys stabilization for lumbar stenosis with or without spondylolisthesis showed good long-term clinical and radiographic results. Lumbar stenosis with or without Grade I spondylolisthesis, particularly in patients

The complete chloroplast genome of Zhangjiajie sage, Salvia daiguii, was assembled in this study. The genome is 151,434 bp in length and contained 134 encoded genes in total, including 88 protein-coding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. The result of phylogenetic analysis based on 17 chloroplast genomes revealed that S. daiguii is clustered with Salvia miltiorrhiza in Lamiaceae.

Tagetes erecta is an important ornamental and medicinal plant indigenous to Mexico and Guatemala. The complete chloroplast genome of T. erecta was newly sequenced in this study. The total chloropalst genome size of T. erecta was 152,055 bp. In total, 123 genes were indetified, including 79 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. Twelve genes are containing introns (ycf3 and clpP contained two introns). The overall GC content of this genome was 37.4%. A further phylogenomic analysis of Asteraceae, including 23 taxa, was conducted for the placement of genus Tagetes. The complete plastome of T. erecta will provide a valuable resource for further genetic conservation, evolution, and molecular breading studies in Asteraceae.

Background: This study evaluated the efficacy of percutaneous nucleoplasty using coblation technique for the treatment of chronic nonspecific low back pain (LBP), after 5 years of follow-up. Methods: From September 2004 to November 2006, 172 patients underwent percutaneous nucleoplasty for chronic LBP in our department. Forty-one of these patients were followed up for a mean period of 67 months. Nucleoplasty was performed at L3/4 in 1 patient; L4/5 in 25 patients; L5/S1 in 2 patients; L3/4 and L4/5 in 2 patients; L4/5 and L5/S1 in 7 patients; and L3/4, L4/5, and L5/S1 in 4 patients. Patients were assessed preoperatively and at 1 week, 1 year, 3 years, and 5 years postoperatively. Pain was graded using a 10-cm Visual Analogue Scale (VAS) and the percentage reduction in pain score was calculated at each postoperative time point. The Oswestry Disability Index (ODI) was used to assess disability-related to lumbar spine degeneration, and patient satisfaction was assessed using the modified MacNab criteria. Results: There were significant differences among the preoperative, 1-week postoperative, and 3-year postoperative VAS and ODI scores, but not between the 3- and 5-year postoperative scores. There were no significant differences in age, sex, or preoperative symptoms between patients with effective and ineffective treatment, but there were significant differences in the number of levels treated, Pfirrmann grade of intervertebral disc degeneration, and provocative discography findings between these two groups. Excellent or good patient satisfaction was achieved in 87.9% of patients after 1 week, 72.4% after 1 year, 67.7% after 3 years, and 63.4% at the last follow-up. Conclusions: Although previously published short- and medium-term outcomes after percutaneous nucleoplasty appeared to be satisfactory, our long-term follow-up results show a significant decline in patient satisfaction over time. Percutaneous nucleoplasty is a safe and simple technique, with therapeutic effectiveness for the treatment of chronic LBP in selected patients. The technique is minimally invasive and can be used as part of a stepwise treatment plan for chronic LBP.

Background: Posterior cervical decompression is an accepted treatment for multilevel cervical spondylotic myelopathy (CSM). Each posterior technique has its own advantages and disadvantages. In the present study, we compared the functional and radiological outcomes of expansive hemilaminectomy and laminoplasty with mini titanium plate in the treatment of multilevel CSM. Methods: Forty-four patients with multilevel CSM treated with posterior cervical surgery in Department of Orthopedic Surgery, Beijing Army General Hospital from March 2011 to June 2012 were enrolled in this retrospective study. Patients were divided into two groups by surgical procedure: Laminoplasty (Group L) and hemilaminectomy (Group H). Perioperative parameters including age, sex, duration of symptoms, operative duration, and intraoperative blood loss were recorded and compared. Spinal canal area, calculated using AutoCAD ® software(Autodesk Inc., San Rafael, CA, USA), and neurological improvement, evaluated with Japanese Orthopedic Association score, were also compared. Results: Neurological improvement did not differ significantly between groups. Group H had a significantly shorter operative duration and significantly less blood loss. Mean expansion ratio was significantly greater in Group L (77.83 ± 6.41%) than in Group H (62.72 ± 3.86%) (P < 0.01). Conclusions: Both surgical approaches are safe and effective in treating multilevel CSM. Laminoplasty provides a greater degree of enlargement of the spinal canal, whereas expansive hemilaminectomy has the advantages of shorter operative duration and less intraoperative blood loss.

The article discusses the importance of machine vision in real-time applications like autonomous driving and robotics, emphasizing the need for efficient and low-power image processing directly at sensory terminals. It introduces a novel approach using ion-induced localized-field modulation to achieve nonvolatile responsivity modulation in a broadband retinomorphic vision sensor, including convolutional processing and artificial neural networks.

BACKGROUND: Several epidemiological investigations demonstrated that maternal arsenic (As) exposure elevated risk of fetal growth restriction (FGR), but the mechanism remains unclear. OBJECTIVES: This study aimed to investigate the effects of gestational As exposure on placental and fetal development and its underlying mechanism. METHODS: Dams were exposed to 0.15, 1.5, and 15 mg/L NaAsO2 throughout pregnancy via drinking water. Sizes of fetuses and placentas, placental histopathology, and glycogen content were measured. Placental RNA sequencing was conducted. Human trophoblasts were exposed to NaAsO2 (2 μM) to establish an in vitro model of As exposure. The mRNA stability and protein level of genes identified through RNA sequencing were measured. 푁6-Methyladenosine (m6A) modification was detected by methylated RNA immunoprecipitation–quantitative real-time polymerase chain reason (qPCR). The binding ability of insulin-like growth factor 2 binding protein 2 to the gene of interest was detected by RNA-binding protein immunoprecipitation-qPCR. Intracellular S-adenosylmethionine (SAM) and methyltransferase activity were determined by liquid chromatography– tandem mass spectrometry (LC-MS/MS) and colorimetry, respectively. In vitro As+3 methyltransferase (As3MT) knockdown or SAM supplementation and in vivo folic acid (FA) supplementation were used to evaluate the protective effect. A case–control study verified the findings. RESULTS: Sizes of fetuses (exposed to 1.5 and 15 mg/L NaAsO2) and placentas (exposed to 15 mg/L NaAsO2) were lower in As-exposed mice. More glycogen+ trophoblasts accumulated and the expression of markers of interstitial invasion was lower in the 15 mg/L NaAsO2-exposed mouse group in comparison with control. Placental RNA sequencing identified cysteine-rich angiogenic inducer 61 (Cyr61) as a candidate gene of interest. Mechanistically, mice and cells exposed to As had lower protein expression of CYR61, and this was attributed to a lower incidence of Cyr61 m6A. Furthermore, cells exposed to As had lower methyltransferase activity, suggesting that this could be the mechanism by which Cyr61 m6A was affected. Depletion of intracellular SAM, a cofactor for m6A methyltransferase catalytic domain, partially contributed to As-induced methyltransferase activity reduction. Either As3MT knockdown or SAM supplementation attenuated As-induced Cyr61 m6A down-regulation. In mice, FA supplementation rescued As-induced defective trophoblastic invasion and FGR. In humans, a negative correlation between maternal urinary As and plasma CYR61 was observed in infants who were small for gestational age. DISCUSSION: Using in vitro and in vivo models, we found that intracellular SAM depletion–mediated Cyr61 m6A down-regulation partially contributed to As-induced defective trophoblastic invasion and FGR. [ABSTRACT FROM AUTHOR]