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Abstract Objective This study aims to explore ADH4 expression in hepatocellular carcinoma (HCC), its prognostic impact, and its immune correlation to provide novel insights into HCC prognostication and treatment. Methods HCC prognostic marker genes were rigorously selected using GEO database, Lasso regression, GEPIA, Kaplan-Meier and pROC analyses. The expression of interested markers (ADH4, DNASE1L3, RDH16, LCAT, HGFAC) in HCC and adjacent tissues was assessed by Immunohistochemistry (IHC). We observed that ADH4 exhibited low expression levels in liver cancer tissues and high expression levels in normal liver tissues. However, the remaining four genes did not manifest any statistically significant differences between hepatocellular carcinoma (HCC) tissue and adjacent non-cancerous tissue. Consequently, ADH4 became the primary focus of our research. ADH4 expression was validated by signed-rank tests and unpaired Wilcoxon rank sum tests across pan-cancer and HCC datasets. Clinical significance and associations with clinicopathological variables were determined using Kaplan-Meier, logistic regression and Cox analyses on TCGA data. The ADH4-related immune responses were explored by Spearman correlation analysis using TIMER2 data. CD68, CD4, and CD19 protein levels were confirmed by IHC in HCC and non-cancerous tissues. Results ADH4 showed significant downregulation in various cancers, particularly in HCC. Moreover, low ADH4 expression was associated with clinicopathological variables and served as an independent prognostic marker for HCC patients. Additionally, ADH4 affects a variety of biochemical functions and may influence cancer development, prognosis, and treatment by binding to immune cells. Furthermore, at the immune level, the low expression pattern of ADH4 is TME-specific, indicating that ADH4 has the potential to be used as a target for cancer immunotherapy. Conclusion This study highlights the diagnostic, prognostic and immunomodulatory roles of ADH4 in HCC. ADH4 could serve as a valuable biomarker for HCC diagnosis and prognosis, as well as a potential target for immunotherapeutic interventions.

Background As women with low ovarian reserve embark on the challenging journey of in-vitro fertilisation (IVF) treatment, the choice between natural and mildly stimulated cycles becomes a pivotal consideration. It is unclear which of these two regimens is superior for women with low ovarian reserve. Our study aims to assess the impact of natural cycles on embryo quality and pregnancy outcomes in women with low ovarian reserve undergoing IVF treatment compared to mildly stimulated cycles.Methods This retrospective study enrolled consecutive patients with low ovarian reserve who underwent IVF/intracytoplasmic sperm injection (ICSI) at Guangdong Second Provincial General Hospital between January 2017 and April 2021. The primary outcome for pregnancy rate of 478 natural cycles and 448 mild stimulated cycles was compared. Secondary outcomes included embryo quality and oocyte retrieval time of natural cycles.Results The pregnancy rate in the natural cycle group was significantly higher than that in the mildly stimulated cycle group (51.8% vs. 40.1%, p = 0.046). Moreover, natural cycles exhibited higher rates of available embryos (84.1% vs. 78.6%, p = 0.040), high-quality embryos (61.8% vs. 53.2%, p = 0.008), and utilisation of oocytes (73% vs. 65%, p = 0.001) compared to mildly stimulated cycles. Oocyte retrievals in natural cycles were predominantly performed between 7:00 and 19:00, with 94.9% occurring during this time frame. In natural cycles with high-quality embryos, 96.4% of oocyte retrievals were also conducted between 7:00 and 19:00.Conclusion Natural cycles with appropriately timed oocyte retrieval may present a valuable option for patients with low ovarian reserve.

Abstract Objective To investigate whether intrauterine chilled saline can reduce endometrial impairment during US-guided percutaneous microwave ablation (PMWA) of adenomyosis. Methods An open-label, randomized trial was conducted with sixty symptomatic adenomyosis patients who were randomly assigned (1:1) to receive PMWA treatment assisted by intrauterine saline instillation (study group) or traditional PMWA treatment alone (control group). The primary endpoint was endometrial perfusion impairment grade on post-ablation contrast-enhanced MRI. The secondary endpoints were endometrial dehydration grade, ablation rate, and intra-ablation discomfort. Results The baseline characteristics of the two groups were similar. The incidence rates of endometrial perfusion impairment on MRI in the study and control groups were 6.7% (2/30) and 46.7% (14/30), respectively (p

Polymorphism is universal in energetic materials (EMs), which is originated from the differences of molecular conformers and stacking mode. The polymorphic transition may lead to the change of crystal structure and properties of EMs. In this work, β-Hx2TNBI·2H2O (β-1) was successfully synthesized through solvent-induced conformational transition of Hx2TNBI·2H2O. From the perspective of quantum chemistry and molecular dynamics, the crystal stacking changes caused by different molecular conformations are discussed in detail, which leads to the properties difference of EMs. The results show that β-1 featured wave-like crystal stacking, making it less sensitive to external mechanical stimuli than α-Hx2TNBI·2H2O (α-1) (α-1: IS > 6 J, FS > 288 N; β-1: IS > 20 J, FS > 360 N). α-1 featured better the aromaticity, which gives it higher thermal stability than β-1 (α-1: Td = 186 °C; β-1: Td = 146 °C). Simultaneously, compared with β-1, α-1 has higher crystal density and detonation performance. This work provides a new and effective way to change the safety of EMs.

Abstract Objective The study aimed to investigate the predictive value of dynamic contrast-enhanced ultrasound (DCE-US) in differentiating small-duct (SD) and large-duct (LD) types of intrahepatic cholangiocarcinoma (ICC). Methods This study retrospectively enrolled 110 patients with pathologically confirmed ICC lesions who were subject to preoperative contrast-enhanced ultrasound (CEUS) examinations between January 2022 and February 2023. Patients were further classified according to the subtype: SD-type and LD-type, and an optimal predictive model was established and validated using the above pilot cohort. The test cohort, consisting of 48 patients prospectively enrolled from March 2023 to September 2023, was evaluated. Results In the pilot cohort, compared with SD-type ICCs, more LD-type ICCs showed elevated carcinoembryonic antigen (p

Abstract Hedyotis diffusa Willd (HDW) possesses heat-clearing, detoxification, anti-cancer, and anti-inflammatory properties. However, its effects on rheumatoid arthritis (RA) remain under-researched. In this study, we identified potential targets of HDW and collected differentially expressed genes of RA from the GEO dataset GSE77298, leading to the construction of a drug-component-target-disease regulatory network. The intersecting genes underwent GO and KEGG analysis. A PPI protein interaction network was established in the STRING database. Through LASSO, RF, and SVM-RFE algorithms, we identified the core gene MMP9. Subsequent analyses, including ROC, GSEA enrichment, and immune cell infiltration, correlated core genes with RA. mRNA–miRNA–lncRNA regulatory networks were predicted using databases like TargetScan, miRTarBase, miRWalk, starBase, lncBase, and the GEO dataset GSE122616. Experimental verification in RA-FLS cells confirmed HDW’s regulatory impact on core genes and their ceRNA expression. We obtained 11 main active ingredients of HDW and 180 corresponding targets, 2150 RA-related genes, and 36 drug-disease intersection targets. The PPI network diagram and three machine learning methods screened to obtain MMP9, and further analysis showed that MMP9 had high diagnostic significance and was significantly correlated with the main infiltrated immune cells, and the molecular docking verification also showed that MMP9 and the main active components of HDW were well combined. Next, we predicted 6 miRNAs and 314 lncRNAs acting on MMP9, and two ceRNA regulatory axes were obtained according to the screening. Cellular assays indicated HDW inhibits RA-FLS cell proliferation and MMP9 protein expression dose-dependently, suggesting HDW might influence RA’s progression by regulating the MMP9/miR-204-5p/MIAT axis. This innovative analytical thinking provides guidance and reference for the future research on the ceRNA mechanism of traditional Chinese medicine in the treatment of RA.

Purpose This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis. Methods This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up. Results No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P

Background The certification of immunogenicity consistency at different production scales is indispensable for the quality control of vaccines. Research design and methods A randomized, double-blind immunobridging trial in healthy adults aged 18–59 was divided into Scale A (50 L and 800 L) and Scale B (50 L and 500 L) based on vaccine manufacturing scales. Eligible participants in Scale A were randomly assigned to receive the single-dose recombinant adenovirus type-5 vectored COVID-19 vaccine (Ad5-nCoV) of different scales at a 1:1 ratio, as was Scale B. The primary endpoint was the geometric mean titer (GMT) of anti-live SARS-CoV-2-specific neutralizing antibodies (NAb) 28 days post-vaccination. Results 1,012 participants were enrolled, with 253 (25%) per group. The post-vaccination GMTs of NAb were 10.72 (95% CI: 9.43, 12.19) and 13.23 (11.64, 15.03) in Scale A 50 L and 800 L, respectively; 11.64 (10.12, 13.39) and 12.09 (10.48, 13.95) in Scale B 50 L and 500 L, respectively. GMT ratios in Scale A and B have a 95% CI of 0.67–1.5. Most adverse reactions were mild or moderate. 17 of 18 participants reported non-vaccination-related serious adverse reactions. Conclusions The Ad5-nCoV in the scale-up production of 500 L and 800 L showed consistent immunogenicity with the original 50 L production scale, respectively.

AIM: To investigate the refractive status and myopia wearing rate of primary and secondary school students aged 6-18 in Yecheng county, Xinjiang.METHOD: Cross-sectional study. From October 2021 to June 2022, a stratified random sampling method was used to select 81 863 students from 51 primary schools and 30 secondary schools in Yecheng county, Kashgar Prefecture, Xinjiang. Basic data of the students were collected, and non ciliary muscle paralysis optometry was performed to detect naked eye farsightedness and corrected vision with glasses. The refractive status, glasses wearing rate, and full correction rate of students of different ages, genders, and ethnic groups were observed.RESULT: The detection rate of myopia among enrolled students was 13.39%(10958/81863), the wearing rate of glasses was 23.96%(2626/10958), and the full correction rate was 50.57%(1328/2626). The detection rate of myopia shows a certain upward trend with age, and the detection rate of myopia in girls was higher than that in boys(15.75% vs. 10.96%). The detection rates of myopia in Han, Uyghur, and other ethnic students were 68.12%, 12.63%, and 22.42%, respectively.CONCLUSION:The detection rate of myopia and glasses wearing rate were relatively low for students aged 6～18 in Yecheng county, Xinjiang, while the detection rate and glasses wearing rate of myopia among Han students were significantly higher than those of Uyghur and students of other ethnics.

AIM: To investigate the differences of myopia and ocular biological parameters of primary and middle school students in Urumqi.METHODS: A cross-sectional survey. A total of 2 495 primary and middle school students aged 7 to 18 from 4 schools in Urumqi were selected by judgemental sampling from September 2021 to November 2021 for relevant eye examination. The differences of ocular biological parameters and refractive status of students of different ages, genders and nationalities were compared, and the correlation between spherical equivalent(SE)and ocular biological parameters was analyzed.RESULTS: The detection rate of poor vision among the students was 80.36%, the detection rate of myopia was 55.91%, and the detection rate of astigmatism was 42.96%, among which the detection rate of low myopia was 63.80%, the detection rate of moderate myopia was 27.60%, and the detection rate of high myopia was 8.60%. There were significant differences in the detection rate of poor vision, myopia, astigmatism, SE and some ocular biological parameters among students of different ages and nationalities(all P

Background: Given that limited reports have described the survival and risk factors for elderly patients with hypertensive intracerebral hemorrhage (HICH), we aimed to develop a valid but simple prediction nomogram for the survival of HICH patients. Methods: All elderly patients ≥65 years old who were diagnosed with HICH between January 2011 and December 2019 were identified. We performed the least absolute shrinkage and selection operator (Lasso) on the Cox regression model with the R package glmnet. A concordance index was performed to calculate the nomogram discrimination; and calibration curves and decision curves were graphically evaluated by depicting the observed rates against the probabilities predicted by the nomogram. Results: A total of 204 eligible patients were analyzed, and over 20 % of the population was above the age of 80 (65–79 years old, n = 161; 80+ years old, n = 43). A hematoma volume ≥13.64 cm3 was associated with higher 7-day mortality (OR = 6.773, 95 % CI = 2.622–19.481; p

Purpose Thermal ablation (TA) is a minimally invasive treatment method for symptomatic benign thyroid nodules (BTNs). This study aimed to evaluate the value of TA by comparing the efficacy, safety, and patient satisfaction with conventional/open thyroidectomy (ConT) and endoscopic thyroidectomy (ET) for symptomatic BTNs. Methods Patients with symptomatic BTNs who underwent ConT, ET, or TA therapy between January 2018 and January 2020 were included. Pre-operation data of the two comparisons (TA vs. ConT and TA vs. ET) was balanced using propensity score matching. The technique efficacy (volume reduction ratio ≥50%), nodule disappearance, and regrowth rate were calculated after ablation. The operation and hospitalization time, medical cost, complications, post-operative symptoms, and cosmetic scores were recorded and compared. Patient satisfaction was evaluated using a telephone survey. Results After a median 19-month follow-up (range, 12–36 months), the technique efficacy rate, nodule disappearance, and regrowth rate were 93.2% (119/129), 6.8% (10/129), and 0.8% (1/129), respectively. Operation time, hospitalization time, and medical costs were less for patients in the TA group than for patients in the ConT and ET groups (all p 0.05). Post-operative hypothyroidism was less frequent in the TA group than in the ConT and ET groups (all p

AIM: To evaluate the prevalence and potential risk factors of dry eye among residents in Hotan, Xinjiang, China.METHODS: A cross-sectional study was conducted on 6 027 residents aged 18-98 from 105 villages in Hotan, Xinjiang, China from January 2019 to September 2019. The subjective symptoms of dry eye were collected by ocular surface disease index(OSDI)questionnaire, and the objective signs were collected by testing fluorescein breakup time(FBUT)and Schirmer Ⅰ test, so as to analyze the prevalence and risk factors of dry eye.RESULTS: A total of 6 339 subjects aged 18-98 years were recruited from residents in Hotan, Xinjiang, China. Relevant eye examinations and questionnaires were conducted on the subjects, of which 6 027 were valid questionnaires, with an effective recovery rate of 95.08%. The dry eye detection rate of 6 027 residents was 40.37%(2 433/6 027), and the dry eye detection rates of male and female were 36.47%(846/2 320)and 42.81%(1 587/3 707)respectively. The dry eye detection rates of 18-24 years old, 25-34 years old, 35-44 years old, 45-54 years old, 55-64 years old, and ≥65 years old were 13.77%, 15.67%, 33.31%, 46.35%, 47.65%, 53.50%, respectively. According to the severity of dry eye, they were divided into mild dry eye, moderate dry eye and severe dry eye, and their constituent ratios were 80.11%, 19.03% and 0.86%, respectively.CONCLUSION: The prevalence of dry eye in the study population was 40.37%. The prevalence of dry eye in female was higher than that in male, and the prevalence of dry eye increased with the increase of age. Older age and female are the risk factors for dry eye.

Purpose This study investigated the value of synchronous tele-ultrasonography (TUS) for naive operators in thyroid ultrasonography (US) examinations. Methods Ninety-seven patients were included in this prospective, parallel-controlled trial. Thyroid scanning and diagnosis were completed by resident A independently, resident B with guidance from a US expert through synchronous TUS, and an on-site US expert. The on-site expert’s findings constituted the reference standard. Two other off-site US experts analyzed all data in a blind manner. Inter-operator consistency between the two residents and the on-site US expert for thyroid size measurements, nodule measurements, nodule features, American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) categories, and image quality was compared. Two questionnaires were completed to evaluate the clinical benefit. Results Resident B detected more nodules consistent with the on-site expert than resident A did (89.4% vs. 56.5%, P0.75), while resident A achieved lower consistency in ACR TI-RADS categories, composition, echogenicity, margin, echogenic foci, and vascularity (all ICCs 0.40-0.75). Residents A and B had excellent consistency in target nodule measurements (all ICCs >0.75). Resident B achieved better performance than resident A for gray values, time gain compensation, depth, color Doppler adjustment, and the visibility of key information (all P

Purpose This prospective study explored the value of synchronous tele-ultrasound (US) to aid doctors inexperienced in US with breast US examinations. Methods In total, 99 patients were enrolled. Two trainee doctors who were inexperienced in US (trainee A [TA] and trainee B [TB]) and one doctor who was an expert in US completed the US examinations sequentially. TA completed the US examinations independently, while TB was instructed by the expert using synchronous tele-US. Subsequently, the expert performed on-site US examinations in person. Separately, they selected the most clinically significant nodule as the target nodule. Consistency with the expert and image quality were compared between TA and TB to evaluate tele-US. Furthermore, TB and the patients evaluated tele-US through questionnaires. Results TB demonstrated higher consistency with the expert in terms of target nodule selection than TA (93.3% vs. 63.3%, P0.75) with the expert on five US features (5/9, 55.6%), while TA only did so for one (1/9, 11.1%) (P=0.046). TB’s image quality was higher than TA’s in gray value, time gain compensation, depth, color Doppler adjustment, and the visibility of key information (P=0.018, P

Grain water relations play an important role in grain filling in maize. The study aimed to gain a clear understanding of the changes in grain dry weight and water relations in maize grains by using hybrids with contrasting nitrogen efficiencies under differing nitrogen levels. The objectives were: 1) to understand the changes in dry matter and percent moisture content (MC) during grain development in response to different nitrogen application rates and 2) to determine whether nitrogen application affects grain filling by regulating grain water relations. Two maize hybrids, high N-efficient Zhenghong 311 (ZH311) and low N-efficient Xianyu 508 (XY508), were grown in the field under four levels of N fertilizer: 0, 150, 300, and 450 kg N ha–1 during three growing seasons. Dry weight, percent MC and water content (WC) of basal–middle and apical grains were investigated. The difference in the maximum WC and filling duration of basal–middle and apical grains in maize ears resulted in a significant difference in final grain weight. Grain position markedly influenced grain drying down; specifically, the drying down rate of apical grains was faster than that of basal–middle grains. Genotype and grain position both influenced the impact of nitrogen application rate on grain filling and drying down. Nitrogen rate determined the maximum grain WC and percent MC loss rate in the middle and the late grain-filling stages, thus affecting final grain weight. The use of high N-efficient hybrids, combined with the reduction of nitrogen application rate, can coordinate basal–middle and apical grain drying down to ensure yield. This management strategy could lead to a win–win situation in which the maximum maize yield, efficient mechanical harvest and environmental safety are all achieved.

Abstract Background Physical activity is known to have anti-cancer effects, including immunomodulatory actions. This study investigated the hypothesis that physical activity synergizes with combined lenvatinib plus anti-PD-1 therapy to enhance efficacy in patients with unresectable HCC. Methods The physical activity levels of patients with unresectable HCC receiving combined lenvatinib plus anti-PD-1 therapy were recorded by questionnaire. Patients were categorized according to physical activity levels (active vs. sedentary). The primary outcome was overall survival (OS). Secondary outcomes included objective response rate (ORR) and progression-free survival (PFS). A subcutaneous syngeneic HCC model was generated in C57BL/6 mice. Mice were randomized to receive placebo, combined lenvatinib plus anti-PD-1 antibodies or combination therapy plus physical activity. Tumors were measured every 3 days and harvested for immunohistochemistry analysis at 20 mm maximum diameter. Results Fifty-nine patients with unresectable HCC were categorized to active (n = 28) or sedentary (n = 31) groups. The active group had higher albumin and des-γ-carboxy prothrombin levels and lower hepatitis B virus load at baseline; other clinical and oncologic characteristics were comparable between the two groups. Patients in the active group had significantly longer OS (HR = 0.220, 95% CI 0.060–0.799) and PFS (HR = 0.158, 95% CI 0.044–0.562) and higher ORR (OR = 4.571, 95% CI 1.482–14.102) than patients in the sedentary group. Regular physical activity was independently associated with OS, PFS and ORR. The mouse model showed that physical activity significantly suppressed tumor growth and prolonged survival of tumor-bearing mice. Furthermore, physical activity inhibited Treg cell infiltration and immune checkpoint expression (including CTLA4, TIGIT and TIM3) induced by long-term combined lenvatinib plus anti-PD-1 therapy, improving efficacy. Conclusions Regular physical activity was associated with improved outcomes in unresectable HCC receiving combined lenvatinib plus anti-PD-1 therapy. Physical activity may improve therapeutic efficacy by reprograming the tumor microenvironment from an immunosuppressive to immunostimulatory phenotype.

Background and purposeThe first-pass recanalization of endovascular treatment (EVT) is closely correlated with clinical outcome of patients with large vessel occlusion (LVO) stroke. The aim of the study was to explore whether intra-arterial tenecteplase (TNK) during the first pass of EVT can increase first-pass successful reperfusion and improve the neurological outcome in AIS-LVO patients.Materials and methodsThe BRETIS-TNK trial (ClinicalTrials.gov Identifier: NCT04202458) was a prospective, single-arm, single center study. Twenty-six eligible AIS-LVO patients with large-artery atherosclerosis etiology were consecutively enrolled from December 2019 to November 2021. Intra-arterial TNK (4 mg) after microcatheter navigation through the clot was administered, followed by TNK (0.4 mg/min) given continuously for 20 min after the first retrieval attempt of EVT without confirmation of the reperfusion status by DSA. The 50 control patients comprised of a historical cohort before the BRETIS-TNK trial (from March 2015 to November 2019). Successful reperfusion was defined as modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b.ResultsThe first-pass successful reperfusion rate was higher in the BRETIS-TNK vs. control group (53.8% vs. 36%, p = 0.14), and the difference became statistically significant after propensity score matching (53.8% vs. 23.1%, p = 0.03). There was no difference in symptomatic intracranial hemorrhage between the BRETIS-TNK and control groups (7.7% vs. 10.0%, p = 0.92). There was a trend toward higher proportion of functional independence at 90 days in the BRETIS-TNK comparing with the control group (50% vs. 32%, p = 0.11).ConclusionThis is the first study to report that intra-arterial TNK during the first pass of EVT seems safe and feasible in AIS-LVO patients.

With the vigorous development of network technology, optical networks are developing in the direction of ultra-highspeed and large-capacity. Since the structure of the optical network is becoming more complex.the optical signal will inevitably suffer various impairments in the optical network. In optical communication equipment, the most important parameter of the physical layer is the Optical Signal-to-Noise Ratio (OSNR). Its value directly determines whether the service can operate normally. Once the requirements are not met, it will cause transmission errors or failures, reducing service quality, and transmission consumption. This paper proposes an accurate and efficient OSNR prediction method for optical communication nodes. By combining analytic prior knowledge methods and deep learning-based posterior knowledge methods, an optical communication node OSNR based on hybrid machine learning algorithms are proposed. The prediction method uses prior knowledge to reduce the training cost of neural networks and provides high-accuracy OSNR predictions. The result shows that the method proposed in this paper can provide high-accuracy machine learning models under more demanding conditions.

Summary: The directional rebound and transport of water droplets plays an important role in microfluidic devices, anti-fogging, and water harvesting. Herein, an extrusion compression molding and directional stretch demolding method was used to prepare a polypropylene (PP) surface with tilt micro/nanopillars with a contact angle of 157 ± 3°. The rolling angle is the highest (9 ± 4°) when the direction of rotation is opposite the tilt direction of the micro/nanopillars, showing excellent water repellency and anisotropy of the surface. Compared with the position of the first collision of the water droplet, the position of the second collision shifted ∼1.5 mm along the tilt direction of the micro/nanopillars, driven by the surface tension component during the collision. The directional rebound behavior is controlled by the droplet energy and the tilt angle. The micro/nanopillars demonstrate excellent self-cleaning property and mechanical durability, which shows the possibility of their practical engineering applications.

The Cr-plated coating inside a gun barrel can effectively improve the barrel’s erosion resistance and thus increase the service life. However, due to the cyclic thermal load caused by high-temperature gunpowder, micro-element damage tends to occur within the Cr coating/steel substrate interface, leading to a gradual deterioration in macro-mechanical properties for the material in the related region. In order to mimic this cyclic thermal load and, thereby, study the thermal erosion behavior of the Cr coating on the barrel’s inner wall, a laser emitter is utilized in the current study. With the help of in-situ tensile test and finite element simulation results, a shear stress distribution law of the Cr coating/steel substrate and a change law of the interface ultimate shear strength are identified. Studies have shown that the Cr coating/steel substrate interface’s ultimate shear strength has a significant weakening effect due to increasing temperature. In this study, the interfacial ultimate shear strength decreases from 2.57 GPa (no erosion) to 1.02 GPa (laser power is 160 W). The data from this experiment is employed to establish a Cr coating/steel substrate interface shear damage model. And this model is used to predict the flaking process of Cr coating by finite element method. The simulation results show that the increase of coating crack spacing and coating thickness will increase the service life of gun barrel.

IntroductionLow back pain (LBP) is the most prevalent form of chronic pain in active-duty military personnel worldwide. Electroacupuncture (EA) and neuromuscular electrical stimulation (NMES) are the two most widely used treatment methods in the military, while evidence for their benefits is lacking. The aim of this randomized clinical trial is to investigate the effectiveness of EA vs. NMES in reducing pain intensity among active-duty navy personals with chronic LBP.MethodsThe study is designed as a single-center, randomized controlled trial. The primary outcome is a positive categorical response for treatment success in the first-time follow-up, which is predesignated as a two-point or greater decrease in the NRS score and combined with a score > 3 on the treatment satisfaction scale. The secondary outcomes include pain intensity, rate of treatment success, and Oswestry Disability Index (ODI) fear-avoidance beliefs questionnaire (FABQ) score along with muscular performance. The first follow-up starts on the first day after completing the last treatment session, and then the 4-weeks and 12-weeks follow-up are applied via telephone visit.ResultsEighty-five subjects complete the treatment diagram and are included in the analysis. For the primary outcome, no difference has been found between EA and NMES, with 65.1% (28 in 43) individuals reporting a positive response to EA treatment, while 53.5% (23 in 43) in NMES. However, for longer follow-ups, superiority in positive response of EA has been found in 4-weeks (26 in 39, 66.7% vs. 16 in 40, 40%; P = 0.018) and 12-weeks (24 in 36, 66.7% vs. 12 in 36, 33.3%; P = 0.005) follow-up. In the regression analysis, baseline pain intensity and FABQ score are identified to be highly associated with positive treatment outcomes. Finally, the subgroup analysis suggests that EA treatment is associated with better long-term outcomes in patients with LBP with a severe pain score (NRS score >4, Figure 4B) and stronger fear-avoidance beliefs.ConclusionBoth the EA and NMES are associated with a positive response in treating military LBP, and the former offers lasting benefits in the later follow-ups. Thus, electroacupuncture is a more recommended treatment for military LBP. A lot of research is needed to verify an efficient and standardized treatment session, with more information and evidence about indications for these treatments.Trial registrationChiCTR, (ChiCTR2100043726); registered February 27, 2021.

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the key enzymes in the process of lipid transport, is involved in the disease progression of various types of tumors. This article is to study the role of PCSK9 in the progression of hepatocellular carcinoma (HCC). Methods Immunohistochemistry was used to assess the expression of PCSK9 in tumor specimens from 105 HCC patients who underwent curative resection. Western blotting and quantitative real-time PCR were used to test the protein and mRNA expression levels in HCC cell lines. Cell Counting Kit-8 (CCK-8) and clone formation assays were performed to evaluate the proliferation ability of different kinds of cells in vitro. Flow cytometry was used to analyze cell cycle distribution and apoptosis rate. A xenograft model was established to study the effect of PCSK9 on HCC growth in vivo. TUNEL and immunofluorescence assays were used to detect cell apoptosis. Results High expression of PCSK9 in tumor tissues was related to microvascular invasion (p = 0.036) and large tumor size (p = 0.001) in HCC patients. Overall survival and disease-free survival after surgery were poor in patients with high expression of PCSK9 (p = 0.035 and p = 0.007, respectively). In vivo and in vitro experiments showed that PCSK9 promoted the growth of HCC by inhibiting cell apoptosis. A mechanistic study revealed that PCSK9 increases FASN expression, thereby inhibiting apoptosis of HCC cells via the Bax/Bcl-2/Caspase9/Caspase3 pathway. Conclusions PCSK9 expression level in HCC is an indicator of poor prognosis for patients with HCC. FASN-mediated anti-apoptosis plays an important role in PCSK9-induced HCC progression.

AIM: To investigate the influence of unilateral congenital ptosis on the development of the eye and vision in children. METHODS: In this prospective observational study, 41 patients with unilateral congenital ptosis were enrolled (age range 3-15y). The blepharoptosis was divided into 3 subgroups according to the margin reflex distance-1 (MRD-1), including mild group (MRD-1≥2 mm), moderate group (0≤MRD-1

AIM: To observe and analyze the ocular surface parameters in patients with type 2 diabetes mellitus and/or hypertension using non-contact ocular comprehensive surface analyzer.METHODS: Totally 160 patients were divided into four groups. And 40 patients were diagnosed with type 2 diabetes mellitus, 40 patients with hypertension, 40 patients with type 2 diabetes mellitus and hypertension, and 40 patients without type 2 diabetes mellitus and hypertension were selected from our hospital from January 2017 to December 2018. OSDI scores, tear meniscus height, eye red index, corneal fluorescein sodium staining scores, non-invasive tear film rupture time(first tear film rupture time and average tear film rupture time)were analyzed and compared among the four groups.RESULTS: The subjective perception of eye discomfort was more obvious in patients with T2DM. Patients with T2DM and/or hypertension were more likely to have eye congestion. Compared with the patients without T2DM and hypertension, the tear meniscus height and average tear film rupture time of T2DM patients were significantly reduced(PP>0.05).CONCLUSION: Non-contact comprehensive ocular surface analyzer can observe the ocular surface characteristics of the patients non-invasively and provide relatively objective quantitative examination results. Ocular stability in patients with T2DM is lower than in patients without T2DM and hypertension, and ocular surface homeostasis of these patients is more likely to be broken.

Abstract Background Pistachio (Pistacia vera), one of the most important commercial nut crops worldwide, is highly adaptable to abiotic stresses and is tolerant to drought and salt stresses. Results Here, we provide a draft de novo genome of pistachio as well as large-scale genome resequencing. Comparative genomic analyses reveal stress adaptation of pistachio is likely attributable to the expanded cytochrome P450 and chitinase gene families. Particularly, a comparative transcriptomic analysis shows that the jasmonic acid (JA) biosynthetic pathway plays an important role in salt tolerance in pistachio. Moreover, we resequence 93 cultivars and 14 wild P. vera genomes and 35 closely related wild Pistacia genomes, to provide insights into population structure, genetic diversity, and domestication. We find that frequent genetic admixture occurred among the different wild Pistacia species. Comparative population genomic analyses reveal that pistachio was domesticated about 8000 years ago and suggest that key genes for domestication related to tree and seed size experienced artificial selection. Conclusions Our study provides insight into genetic underpinning of local adaptation and domestication of pistachio. The Pistacia genome sequences should facilitate future studies to understand the genetic basis of agronomically and environmentally related traits of desert crops.

Spontaneous abortion is an impeding factor for the success rates of human assistant reproductive technology (ART). Causes of spontaneous abortion include not only the pregnant mothers’ health conditions and lifestyle habits, but also the fetal development potential. Evidences had shown that fetal chromosome aneuploidy is associated with fetal spontaneous abortion, however, it is still not definite that whether other genome variants, like copy number variations (CNVs) or loss of heterozygosity (LOHs) is associated with the spontaneous abortion. To assess the relationship between the fetal genome variants and abortion during ART, a chromosomal microarray data including chromosomal information of 184 spontaneous aborted fetuses, 147 adult female patients and 78 adult male patients during ART were collected. We firstly analyzed the relationship of fetal aneuploidy with maternal ages and then compared the numbers and lengths of CNVs (< 4Mbp) and LOHs among adults and aborted fetuses. In addition to the already known association between chromosomal aneuploidy and maternal ages, from the chromosomal microarray data we found that the numbers and the accumulated lengths of short CNVs and LOHs in the aborted fetuses were significantly larger or longer than those in adults. Our findings indicated that the increased numbers and accumulated lengths of CNVs or LOHs might be associated with the spontaneous abortion during ART.

Tourette syndrome (TS) is a developmental neuropsychiatric disorder with onset during childhood. Because of its complex spectrum of phenotypes, the underlying pathophysiology of TS is still unclear. Resting-state functional magnetic resonance imaging demonstrated aberrant spontaneous neural synchronization in conventional frequency band (0.01–0.08 Hz) in TS. No published studies have reported abnormalities of local synchronization across different frequency bands. We estimated the alterations of local synchronization across five bands ranging from 0 to 0.25 Hz. Seventy-nine children with TS and 63 age-, sex-, and handedness-matched healthy children were recruited. Frequency-specific regional homogeneity (ReHo) and independent component analysis were used to identify functional alterations between TS and healthy children. TS patients showed significantly increased ReHo in the left precentral gyrus and decreased ReHo in the right operculum. Abnormal ReHo alterations of the superior frontal gyrus, superior parietal gyrus, anterior cingulate gyrus, putamen, superior temporal gyrus, and operculum were observed in different frequency bands. TS patients showed increased connectivity of the right superior frontal gyrus within the left executive control network. In addition, a significantly negative correlation was found between Yale Global Tic Severity Scale (YGTSS) vocal score and ReHo values of the right operculum in the highest frequency bands (0.198–0.25 Hz), while a significant positive correlation was found between YGTSS motor score and altered connectivity of the right superior frontal gyrus. The present study revealed frequency-specific abnormal alterations of ReHo in the whole brain and altered connectivity within the executive control network of TS children. Its neural importance and clinical practicability require further investigation.

Abstract Background High frequency of recurrence is the major cause of the poor outcomes for patients with hepatocellular carcinoma (HCC). microRNA (miR)-182-5p emerged as a high-priority miRNA in HCC and was found to be related to HCC metastasis. Whether the expression of miR-182-5p in tumor tissue correlated with early recurrence in HCC patients underwent curative surgery was unknown. Methods Real-time PCR (RT-PCR) and in situ hybridization (ISH) were conducted to assess the expression of miR-182-5p in HCC cells and tissues. Cell Counting Kit-8 (CCK-8), transwell assays were performed to detected cells proliferation and migration ability. Flow cytometry assays were used to detect cell apoptosis rate, and xenograft model was employed to study miR-182-5p in HCC growth and lung metastasis. The target of miR-182-5p was validated with a dual-luciferase reporter assay and western blotting. Immunohistochemistry, immumoblotting, and immunoprecipitation were performed to test relative protein expression. Results We showed that high expression of miR-182-5p in tumor tissues correlated with poor prognosis as well as early recurrence in HCC patients underwent curative surgery. miR-182-5p enhanced motility and invasive ability of HCC cells both in vitro and in vivo. miR-182-5p directly targets 3′-UTR of FOXO3a and repressed FOXO3a expression, activating AKT/FOXO3a pathway to promote HCC proliferation. Notably, miR-182-5p activated Wnt/β-catenin signaling by inhibiting the degradation of β-catenin and enhancing the interaction between β-catenin and TCF4 which was mediated by repressed FOXO3a. Conclusions Consistently, miR-182-5p can be a potential predictor of early recurrence for HCC patients underwent curative surgery, and FOXO3a plays a key mediator in miR-182-5p induced HCC progression.

A new relative influence weight function was proposed in combination with the existing linear threshold model.Combining with the information itself sensitivity and the threshold characteristic of the node itself,a threshold model(URLT model) was proposed,which can measure the information communication ability.By simulating the spread of different networks,different sensitivity information and different node thresholds,and comparing the final propagation situation,the experimental results show that the final influence range is consistent with the real spread situation.Therefore,the model has some reference value for the discovery and suppression of the law of information dissemination.

Abstract This study was aimed to evaluatethe usefulness of conventional ultrasound (US) and US elastography, including the latest virtual touch tissue imaging and quantification (VTIQ), in malignancy prediction for complex cystic and solid breast lesions. Eighty-nine complex cystic and solid breast lesions were subject to conventional US and US elastography, including strain elastography (SE), virtual touch tissue imaging (VTI) and VTIQ. Among the 89 lesions, thirty-four (38.2%) lesions were malignant and 55 (61.8%) lesions were benign. Sixteen variables were subject to multivariate logistic regression analysis. Pattern 4b in VTI (odds ratio, OR:15.278), not circumscribed margin of lesion (OR:12.346), SWS mean >4.6 m/s in VTIQ (OR:11.896), and age elder than 50 years (OR:6.303) were identified to be independent predictors for malignancy. In receiver operating characteristic (ROC) curve analyses, associated areas under the ROC curve (Az) for conventional US could be significantly elevated, from 0.649 to 0.918, by combining with US elastography (p

Abstract To evaluate the diagnostic performance of shear wave arrival time contour (SWATC) display for the diagnosis of breast lesions and to identify factors associated with the quality of shear wave propagation (QSWP) in breast lesions. This study included 277 pathologically confirmed breast lesions. Conventional B-mode ultrasound characteristics and shear wave elastography parameters were computed. Using the SWATC display, the QSWP of each lesion was assigned to a two-point scale: score 1 (low quality) and score 2 (high quality). Binary logistic regression analysis was performed to identify factors associated with QSWP. The area under the receiver operating characteristic curve (AUROC) for QSWP to differentiate benign from malignant lesions was 0.913, with a sensitivity of 91.9%, a specificity of 90.7%, a positive predictive value (PPV) of 74.0%, and a negative predictive value (NPV) of 97.5%. Compared with using the standard deviation of shear wave speed (SWSSD) alone, SWSSD combined with QSWP increased the sensitivity from 75.8% to 93.5%, but decreased the specificity from 95.8% to 89.3% (P

Abstract To investigate the diagnostic performance of combination of ultrasound (US) thyroid imaging reporting and data system (TI-RADS) and a new US scoring system for diagnosing thyroid nodules (TNs) with indeterminate results (Bethesda categories III, IV and V) on fine-needle aspiration (FNA) cytology. 453 patients with 453 cytologically indeterminate TNs were included in this study. Multivariate analyses were performed to construct the scoring system. The diagnostic performances of TI-RADS and the combined method were evaluated and compared. Multivariate analyses revealed that marked hypoechogenicity, taller than wide shape and absence of halo sign were independent predictors for malignancy in cytologically indeterminate TNs. Scoring system was thereafter defined as follows: risk score (RS) = 3.2 x (if marked hypoechogenicity) + 2.8 x (if taller than wide shape) + 1.3 x (if absence of halo sign). Compared with TI-RADS alone, the areas under the receiver operating characteristic curves (AUC), specificity, accuracy and positive predictive value (PPV) of the combined method increased significantly with 0.731 versus 0.569, 48.5% versus 14.1%, 76.2% versus 62.3%, and 70.9% versus 59.9%, respectively (all P

Abstract This study aimed to identify the associated factors for quality measurement (QM) of shear wave speed (SWS) imaging and to validate the additional value of QM in the diagnosis of breast lesions. From September 2014 to February 2015, conventional ultrasound and SWS imaging were performed in 338 women with 361 breast lesions. Binary logistic regression was used to identify associated factors for QM. Sensitivity, specificity and the area under receiver operating characteristic (ROC) curve (AUC) among maximum SWS (SWS max ), QM and SWS max plus QM (SWS max +QM) were compared to validate additional value of QM. Pathology confirmed 263 (72.9%) benign lesions and 98 (27.1%) malignancies. Maximum depth (Odds ratio [OR]: 1.398) and posterior features (OR: 1.206) were identified as independent associated factors for QM. Compared with SWS max and QM, the sensitivity of SWS max +QM increased from 67.3%, 64.3% to 83.7% whereas the specificity decreased from 90.5%, 72.6% to 65.4% (all P

Abstract To assess the association between BRAF V600E mutation and ultrasound (US) features in papillary thyroid carcinoma (PTC) patients with and without Hashimoto’s thyroiditis (HT). We retrospectively reviewed the US features and status of BRAF V600E mutation in 438 consecutive patients with surgically confirmed PTCs. The association between BRAF mutation and US features were analyzed. In addition, we conducted subgroup analyses in terms of coexistent HT. The BRAF mutation was found in 86.5% of patients (379 of 438). Patient age (OR: 1.028, P = 0.010), age ≥ 50 y (OR: 1.904, P = 0.030), and microcalcification (OR: 2.262, P = 0.015) on US were significantly associated with BRAF mutation in PTC patients. Solid component (OR: 5.739, P = 0.019) on US was the significant predictor for BRAF mutation in patients with HT, while age (OR: 1.036, P = 0.017) and microcalcification (OR: 3.093, P = 0.017) were significantly associated with BRAF mutation in patients without HT. In conclusion, older age and microcalcification are risk factors for BRAF mutation in PTC patients, especially in those without HT. For those with HT, however, PTCs with BRAF mutation tend to be solid on ultrasound. These factors might be considered when making treatment planning or prognosis evaluation.

Abstract To develop a risk model for predicting axillary lymph node metastasis (LNM) in patients with breast invasive ductal carcinoma (IDCs) using ultrasound (US), US elastography of virtual touch tissue imaging (VTI) and virtual touch tissue imaging & quantification (VTIQ), and histologic parameters. This study included 162 breast IDCs in 162 patients. Univariate and multivariate analyses were used to identify the risk factors and a risk model was created. The results found that 64 (39.5%) of 162 patients had axillary LNMs. The risk score (RS) for axillary LNM was defined as following: RS = 1.3 × (if lesion size ≥20 mm) + 2.6 × (if taller than wide shape) + 2.2 × (if VTI score ≥5) + 3.9 × (if histological grade III) + 1.9 × (if positive C-erbB-2). The rating system was divided into 6 stages (i.e. Stage I, Stage II, Stage III, Stage IV, Stage V, and Stage VI) and the associated risk rates in terms of axillary LNM were 0% (0/19), 6.1% (2/33), 7.7% (3/39), 65.5% (19/29), 92.3% (24/26), and 100% (16/16), respectively. The risk model for axillary LNM established in the study may facilitate subsequent treatment planning and management in patients with breast IDCs.

Functional magnetic resonance imaging (fMRI) studies have shown that the effect of repetitive transcranial magnetic stimulation (rTMS) can induce changes in remote brain regions. In the stimulated regions, low-frequency (≤1 Hz) rTMS induces inhibitory effects, while high-frequency (≥5 Hz) stimulation induces excitatory effects. However, these stereotypical effects arising from low- and high-frequency stimulation are based on measurements of motor evoked potentials (MEPs) induced by pulsed stimulation. To test the effects of rTMS on remote brain regions, the current study recruited 31 young healthy adults who participated in three rTMS sessions (10 Hz high frequency, 1 Hz low frequency, and sham) on three separate days. The stimulation target was based on individual fMRI activation in the motor cortex evoked by a finger movement task. Pre- and post-rTMS resting-state fMRI (RS-fMRI) were acquired. Regional homogeneity (ReHo) and degree centrality (DC) were calculated to measure the local and global connectivity, respectively. Compared with the sham session, high-frequency (10 Hz) rTMS significantly increased ReHo and DC in the right cerebellum, while low-frequency (1 Hz) stimulation did not significantly alter ReHo or DC. Then, using a newly developed PAIR support vector machine (SVM) method, we achieved accuracy of 93.18–97.24% by split-half validation for pairwise comparisons between conditions for ReHo or DC. While the univariate analyses suggest that high-frequency rTMS of the left motor cortex could affect distant brain activity in the right cerebellum, the multivariate SVM results suggest that both high- and low-frequency rTMS significantly modulated widespread brain activity. The current findings are useful for increasing the understanding of the mechanisms of rTMS, as well as guiding precise individualized rTMS treatment of movement disorders.

Alfalfa (Medicago sativa) is a highly valuable perennial forage legume that suffers from autotoxicity, which decreases plant resistance, reduces soil fertility, causes serious soil-borne diseases, and promotes ecological imbalance. We evaluated the effects of autotoxicity on the seed germination of 22 alfalfa varieties, and then elucidated the oxidative damage and lipid peroxidation in two alfalfa varieties with contrasting autotoxicity tolerances. The technique for order of preference by similarity to ideal solution (TOPSIS) method was used to rank the germination of the 22 alfalfa varieties when exposed to six autotoxic concentrations (0, 0.025, 0.075, 0.125, 0.175, and 0.225 g∙mL−1). We found WL656HQ and 3105C to be autotoxicity-tolerant and autotoxicity-sensitive varieties, respectively. The germination index mainly affects the comprehensive allelopathic index of WL656HQ and 3105C, which were the simple vigor index and radicle length according to the random forest model, respectively. 3105C eliminates reactive oxygen species (ROS) via antioxidant enzymes and antioxidants under T1 (0.025 g∙mL−1), but the oxidative stress system and the oxidative scavenging system cannot maintain the balance under T2 (0.125 g∙mL−1), causing oxidative bursts. In comparison, WL656HQ used its oxidative scavenging system (peroxidase (POD), ascorbate peroxidase (APX), and glutathione reductase (GR)) to maintain its redox dynamic balance by removing excess ROS at all concentrations. In conclusion, the positive and negative indicators of autotoxicity for the two varieties were ascorbate (ASA) and hydroxyl free radicals (OH•), and proline (Pro) and dehydroascrobate (DHA), respectively. The most sensitive autotoxic concentrations of 3105C and WL656HQ were T2 (0.125 g∙mL−1) and T1 (0.025 g∙mL−1), respectively.

M2-polarized (alternatively activated) macrophages play an important role in the progression of hepatocellular carcinoma (HCC). Allograft inflammatory factor 1 (AIF1) is overexpressed in M2-polarized macrophages. This study explored the role of AIF1 in tumor-associated macrophages in HCC. Macrophages were stimulated with colony-stimulating factor 1 (CSF1) to characterize the regulatory pathway of AIF1 in macrophages. The chromatin immunoprecipitation and luciferase reporter gene assay were conducted to examine transcription factors associated with AIF1 expression. AIF1 was down or upregulated, and the effects on tumor progression were evaluated by using in vitro and in vivo co-culture systems. A cytokine array was performed to screen the downstream functional components of AIF1. Tumor tissue from 206 patients with HCC were used to explore the clinical significance of AIF1. AIF1 induced a M2-like phenotype of macrophages. By facilitating the binding of c-Jun to the promoter of AIF1, CSF1 secreted from hepatoma cells increased AIF1 expression through the CSF1R-MEK1/2-Erk1/2-c-Jun axis. AIF1 expressed in macrophages promoted the migration of hepatoma cells in co-culture system of RAW264.7 and Hepa1-6 and tumor growth in an animal model. The cytokine array showed that CXCL16 was increased in RAW264.7 cells with overexpressed AIF1, leading to enhanced tumor cell migration. In human HCC tissue, AIF1-positive macrophages in the adjacent microenvironment was associated with microvascular invasion and advanced TNM stages and with patients' overall and disease-free survival (p = 0.002 for both). AIF1 expression in macrophages plays a pivotal role in the interaction between macrophages and hepatoma cells.

The original article [1] contains an error in Fig. 5a whereby the Western blot bands representing CyclinD1 have mistakenly been duplicated over the Western blot bands intended to represent SGK.

OBJECTIVES:The aim of this study was to evaluate the technical and clinical outcomes of using laparoscopic radiofrequency (RF) ablation for treating large subcapsular hepatic hemangiomas. METHODS:We retrospectively reviewed our sequential experience of treating 124 large subcapsular hepatic hemangiomas in 121 patients with laparoscopic RF ablation. RESULTS:The mean diameter of the 124 hemangiomas was 9.1 ± 3.2 cm (5.0-16.0 cm). RF ablation was performed successfully in all patients. There were 55 complications related to the ablation in 26 patients, including 5 of 69 (7.3%) patients with hemangioma

Se-containing precursor films with two different compositions were prepared by magnetron sputtering from and targets, and then were selenized using Se vapor. The effects of precursor composition and selenization temperature on the film properties were investigated. The results show that Se phase plays a critical role in film growth and electrical properties of CIGS films. The Cu-rich films exhibit different surface morphology and better crystallinity, as compared to the Cu-poor films. All the CIGS films exhibit p-type conductivity. The resistivity of the Cu-rich films is about three orders of magnitude lower than that of the Cu-poor films, which is attributed to the presence of p-type highly conductive Se phase.