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Jingyu Zhang,1,&ast; Shenhua Qu,2,&ast; Yuting Huang,1,&ast; Xia Zhang,1 Xiubing Tong,1 Yanping Fang,1 Tianyu Rao,1 Kezhi Liu,1 Jia Lin,1 Yuye Lin,1 Chufan Zeng,1 Guojun Zhang,1 Xianghong Jing,3 Jun Liao,1 Yu Kan1 1College of Acupuncture and Tuina, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People’s Republic of China; 2Guangzhou Traditional Chinese Medicine Hospital, Guangzhou, 510000, People’s Republic of China; 3Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Liao; Yu Kan, Email 2007065@fjtcm.edu.cn; 2019035@fjtcm.edu.cnPurpose: Chronic cervical muscle injury is the first common cause of the development of cervical spondylosis, and Tuina can effectively promote the repair of chronic cervical muscle injury and alleviate neck pain, but the mechanism behind its efficacy is still unknown. The proliferation and differentiation of muscle satellite cells and the apoptosis of cervical myocytes play important roles in the repair of chronic cervical muscle injuries; therefore, this study aimed to explore the potential mechanisms of Tuina to promote the repair of cervical muscle injuries in terms of the proliferation and differentiation of satellite cells and the apoptosis of myocytes.Patients and Methods: Twenty-eight Wistar rats were randomly divided into control group, model group, Tuina group, and meloxicam group, with 7 rats in each group. Except for the control group, each group were establish a chronic cervical muscle injury model (CCMI). Meloxicam (0.79 mg/kg) was administered by gavage, and in the Tuina group, pressure was applied to the Fengchi acupoint on the affected side once a day. Morphological changes of cervical muscle tissues were detected by ultrasonic diagnostic instrument and HE staining, electrophysiological recordings of electromyographic changes, apoptosis rate was detected by TUNEL staining, and positive expression of Bax, Bcl-2, IGF-1, MyoD, and Pax-7 were detected by Immunohistochemistry and Western blot.Results: In CCMI model rats, we observed that the cervical muscle fibers were disorganized, with irregular morphology, and the amplitude of electromyography was significantly weakened, while Tuina could significantly improve these symptoms and effectively promote the repair of chronic cervical muscle injury. Meanwhile, compared with the model group, Tuina could significantly increase the expression levels of IGF-1 (P< 0.01) and MyoD (P< 0.05) and decrease the expression level of Pax7 (P< 0.05). In addition, we found that the number of apoptotic cells in cervical myocytes was reduced after Tuina intervention (P< 0.05), and Tuina inhibited the expression of pro-apoptotic factor Bax (P< 0.01) and promoted the expression of anti-apoptotic factor Bcl-2 (P< 0.05).Conclusion: Tuina can promote the proliferation and differentiation of satellite cells to repair chronic cervical muscle injury by regulating the expression of Pax7, MyoD, and IGF-1, as well as inhibiting the expression of Bax and promoting the expression of Bcl-2 to ameliorate the apoptosis of cervical myocytes in CCMI model rats.Keywords: Tuina, cervical spondylosis, neck pain, satellite cell

Menghui Li,1,2,* Lijuan Wei,1,* Fangxuan Li,1 Yanyan Kan,1 Xiaofeng Liang,1 Huan Zhang,1 Juntian Liu1,2 1Cancer Prevention Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of China; 2National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Menghui Li; Juntian LiuTianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin 300060, People’s Republic of ChinaTel/Fax +86 22-23340123Email limenghui820117@163.com : ljt641024@163.comObjective: Thyroid cancer is the most common primary malignant disorder of the thyroid. We aimed to illustrate the modified TI-RADS report system for differentiating malignant thyroid nodules from benign ones, and especially its role in the management of high risk nodules.Methods: In this retrospective study, 5,162 healthy individuals who underwent thyroid ultrasound according to modified TI-RADS from January 2014 to December 2014 were enrolled and followed up during the whole 5 years, and the medical data were investigated and reviewed.Results: The total detection rate of thyroid nodules was 39.40%. The total detection rate of thyroid cancer was 0.66%. Most thyroid cancers were single-shot, located at unilateral, at early clinical stages, without lymph node metastases, and with low recurrence risk. All patients had thyroid papillary carcinoma, except one thyroid medullary carcinoma. Based on modified TI-RADS classification, at the end of 5 years follow-up, more changes of thyroid nodules grade status were observed in grades 4a and above. The higher the grade status, the more malignant advances were occurred. The modified TI-RADS report system played an instructional role in adding medical treatment choice and decision for clinicians.Conclusion: The modified TI-RADS report system plays an important role in thyroid benign and malignant nodule identification and management.Keywords: thyroid cancer, thyroid nodules, high-risk nodules, thyroid ultrasound, TI-RADS report system

Yanyan Kan,1– 4 Juntian Liu,1– 4 Fangxuan Li1– 4 1Department of Cancer Prevention, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of China; 2National Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 3Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China; 4Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of ChinaCorrespondence: Fangxuan LiDepartment of Cancer Prevention, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin 300060, People’s Republic of ChinaTel/Fax +86-22-23340123Email lifangxuan2008@126.comBackground: Abnormal activation of the nuclear transcription factor-κB (NF-κB) signaling pathway plays a crucial role in the chemoresistance of tumor cells. This study aimed to explore the significance of NF-κB in the chemoresistance of ovarian cancer.Materials: We performed immunohistochemical staining for evaluating the expression of NF-κB in cancer tissues. The MTT assay was performed for analyzing cell proliferation, Western blotting was performed to quantify NF-κB p65, and flow cytometry was used to determine the apoptosis rate.Results: Nuclear NF-κB p65 over-expression was closely associated with ovarian cancer with advanced FIGO stage, residual disease ≥ 1 cm, low histologic grade, platinum resistance and refractory, chemotherapy resistance (P< 0.05). FIGO stage I–II and residual disease < 1 cm were associated with complete response (CR) to chemotherapy, while FIGO stage I–II, residual disease < 1cm and absence of lymph node (LN) metastasis were associated with platinum sensitivity. In multivariate logistic regression, residual disease ≥ 1 cm was a risk factor for response to chemotherapy, while the over-expression of nuclear NF-κB p65 was a risk factor for sensitivity to chemotherapy. In the ROC curves, nuclear NF-κB p65 expression had the discriminative ability for sensitivity to chemotherapy (AUC = 0.637, P = 0.021). Furthermore, nuclear NF-κB p65 expression was an independent prognostic factor. Western blotting showed that NF-κB p65 level in cisplatin-resistant cells (C13* and A2780cp) was significantly higher than that in cisplatin-sensitive cells (OV2008 and A2780s) (P < 0.05), and this increased expression could be suppressed by NF-κB inhibitor-PDTC treatment. The proliferation inhibitory rates of cisplatin in C13* and A2780cp cells increased after PDTC treatment in a concentration-dependent manner. PDTC treatment could also enhance cisplatin-induced apoptosis.Conclusion: NF-κB was associated with the clinicopathological features, chemoresistance, and prognosis of ovarian cancer. The NF-κB inhibitor PDTC can enhance cisplatin sensitivity of platinum-resistant C13* and A2780cp ovarian cancer cells.Keywords: ovarian cancer, NF-κB, cisplatin resistance, chemoresistance, PDTC

Adeno-associated viral vectors (AAV) are attractive tool for gene therapy for coronary artery disease. However, gene expression in myocardium mediated by AAV serotype 2 (AAV2) does not peak until 4-6 weeks after gene transfer. This delayed gene expression may reduce its therapeutic potential for acute cardiac infarction. To determine whether earlier gene expression and better therapeutic effect could be achieved using a different serotype, CMV promoter driving the EPO gene (AAV-EPO) was packaged into AAV serotypes 1-5 capsids and injected into mouse myocardium. EPO expression was studied by measuring the hematocrits and EPO mRNA. After we found that AAV1 mediates the highest gene expression after 4 days of gene transduction, AAV-LacZ (CMV promoter driving LacZ gene expression) and MLCVEGF (hypoxia-inducible and cardiac-specific VEGF expression) were packaged into AAV1 and 2 capsids. LacZ expression was detected in AAV1-LacZ but not in AAV2-LacZ-injected hearts 1 day after vector injection. Compared to AAV2-MLCVEGF that mediated no significant VEGF expression, AAV1-MLCVEGF mediated 13.7-fold induction of VEGF expression in ischemic hearts 4 days after gene transduction and resulted in more neovasculatures, better cardiac function and less myocardial fibrosis. Thus, AAV1 mediates earlier and higher transgene expression in myocardium and better therapeutic effects.

It has been shown that the adeno-associated virus (AAV) vector can deliver the VEGF gene efficiently into the ischemic mouse myocardium. However, the AAV genomes can be found in extracardiac organs after intramyocardial injection. To limit unwanted VEGF expression in organs other than the heart, we tested the use of the cardiac myosin light chain 2v (MLC-2v) promoter and the hypoxia-response element to mediate cardiac-specific and hypoxia-inducible VEGF expression. An AAV vector, MLCVEGF, with 250 bp of the MLC-2v promoter and nine copies of the hypoxia-response element driving VEGF expression, was constructed. Gene expression was studied in vitro by infection of rat cardiomyocytes, rat skeletal myocytes, and mouse fibroblasts with the vector and in vivo by direct injection of the vector into normal and ischemic mouse hearts. With MLCVEGF infection, VEGF expression was higher in cardiomyocytes than the other two cell lines and was hypoxia-inducible. VEGF expression was also higher in ischemic hearts than in normal hearts. No VEGF expression was detectable in organs with detectable MLCVEGF vectors other than the heart. MLCVEGF-injected ischemic hearts had more capillaries and small vessels around the injection site, smaller infarct size, and better cardiac function than the negative controls. Hence, MLCVEGF can mediate cardiac-specific and hypoxia-inducible VEGF expression, neoangio-genesis, infarct-size reduction, and cardiac functional improvement.

Aviation fuel pump has the problem of flow-induced noise in engineering application，which can affect the unit operation stability and staff's working security. To solve these problems，the noise reduction technique for fuel pump is introduced. Firstly，the noise data of fuel pump acquired during the on-land system test of air plane is tested，and the noise amplitude and frequency are analyzed. Then，numerical simulation is conducted to understand the flow regime in the fuel pump. Finally，the optimization design is conducted for impeller and guide vane of fuel pump. The results show that the main reason of flow-induced noise is the pressure fluctuation caused by rotor-stator interaction between impeller and guide vane. The pressure fluctuation can be reduced by increasing the impeller and vane blade number and applying the alternate loading technique. After optimization，the noise of fuel pump is decreased by 6.5 dB.

Abstract Background The recent Maternal Immune Activation (MIA) theory suggests maternal systemic inflammation may serve as a mediator in associations between prenatal maternal adversities and neurodevelopmental diseases in offspring. Given the co-exposure to multiple adversities may be experienced by pregnant person, it is unclear whether a quantitative index can be developed to characterize the inflammation related exposure level, and whether this index is associated with neurodevelopmental delays in offspring. Methods Based on Jiangsu Birth Cohort (JBC), a total of 3051 infants were included in the analysis. Inflammation related Prenatal Adversity Index (IPAI) was constructed using maternal data. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, third edition, screening test in one year. Multivariate linear regression and Poisson regression model were performed to analyze the associations between IPAI and neurodevelopment in offspring. Results Compared with “low IPAI” group, offspring with “high IPAI” have lower scores of cognition, receptive communication, expressive communication, and fine motor. The adjusted β were − 0.23 (95%CI: -0.42, -0.04), -0.47 (95%CI: -0.66, -0.28), -0.30 (95%CI: -0.49, -0.11), and − 0.20 (95%CI: -0.33, -0.06). Additionally, the elevated risk for noncompetent development of cognition and receptive communication among “high IPAI” group was observed. The relative risk [RR] and 95% confidence interval [CI] were 1.35 (1.01, 1.69) and 1.37 (1.09, 1.72). Conclusions Our results revealed a significant association between higher IPAI and lower scores across cognition, receptive communication, expressive communication, and fine motor domains, and an increased risk of noncompetent development in the cognition and receptive communication domains.

Abstract Palbociclib combined with endocrine therapy is approved for treating patients with hormone-receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer; however, data on palbociclib combined with tamoxifen are limited. We investigated the efficacy and safety of palbociclib–tamoxifen in patients with HR+/HER2− advanced breast cancer. This double-blind phase 3 study included 184 women who were randomly assigned 1:1 to receive palbociclib–tamoxifen or placebo–tamoxifen. Pre/perimenopausal women also received goserelin. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. Median PFS was 24.4 months (95% confidence interval [CI], 13.1–32.4) with palbociclib–tamoxifen and 11.1 months (95% CI, 7.4–14.6) with placebo–tamoxifen (hazard ratio [HR], 0.60; 95% CI, 0.43–0.85; P = 0.002). Palbociclib–tamoxifen improved PFS in patients who were treated with first-line or second-line endocrine therapy and pre-, peri-, and postmenopausal patients. Though OS data are still immature (median not reached in both groups), an overall risk reduction of 27% (HR, 0.73; 95% CI, 0.44–1.21) with palbociclib–tamoxifen was observed at the time of PFS analysis. The most common grade 3/4 adverse event with palbociclib–tamoxifen was neutropenia (89.0% [none were febrile] versus 1.1% with placebo–tamoxifen). There were no deaths owing to adverse events in either group. Among patients with HR+/HER2− advanced breast cancer, palbociclib–tamoxifen resulted in significantly longer PFS than tamoxifen alone. Early OS data showed a trend favoring palbociclib–tamoxifen. Trial registration: ClinicalTrials.gov number, NCT03423199. Study registration date: February 06, 2018.

ObjectiveTo describe different non-alcoholic fatty liver disease （NAFLD） outcomes among community inhabitants， and further to explore the correlation between bio-indicator level variance and the outcomes.MethodsPhysical indicators （height， weight， waist circumstances， hip circumstances， blood pressure， etc）， biochemical indicators ［fasting plasma glucose， HbA1c， serum triglycerides（TG）， serum total cholesterol（TC）， low-density lipoprotein cholesterol（LDL-C）， high-density lipoprotein cholesterol（HDL-C）， liver related transaminase， etc］ and clinical imaging （B-scan ultrasonography） were collected during the follow-up from the Songjiang Natural Population Sub-cohort. The identification of NAFLD was supported by the definition criteria from Guidelines for the diagnosis and treatment of non⁃alcoholic fatty liver disease. Paired t-test and multifactorial logistic regression model were used to compare the difference between the indicator level of the subjects from different outcome subgroups and to further analyze the correlation between these indicator variance and different NAFLD outcomes.ResultsDuring a median follow-up time of 2.94 years， 12 076 subjects were involved. The cumulative NAFLD incidence and remission rate were 21.57% and 31.15%， respectively. The proportion of subjects who still had NAFLD was 27.96%. Among subjects with newly-developed NAFLD， indicators including blood pressure， BMI， fasting plasma glucose， and plasma lipid level increased， while in the remission subgroup， blood pressure， BMI（WHR）， waist-hip ratio（WHR）， and TG level were significantly decreased. Increased level of systolic pressure， WHR， BMI， HbA1c， and LDL-C might be the risk factors to the occurrence of NAFLD. While decreased level of WHR， BMI， TC and LDL-C level and elevated HDL-C level were likely to be the influencing factors of NAFLD remission process.ConclusionThe NAFLD morbidity in the community inhabitants is relatively high. BMI， WHR， fasting plasma sugar and plama lipid level variance may act as the influencing factors towards different NAFLD outcomes.

Background: Biomarkers to predict the recurrence risk are required to optimize perioperative treatment. Adjuvant chemotherapy for patients with human epidermal growth factor 2-positive (HER2-positive) early breast cancer is decided by pathological responses of neoadjuvant chemotherapy (NAC). However, whether pathological responses are appropriate biomarkers is unclear. Currently, there are several studies using minimal residual disease (MRD) as a predictor of prognosis in solid tumors. However, there is no standard method for detecting MRD. Objectives: This study aimed at prospectively evaluating the relationship between MRD detection and recurrence in Asian patients with HER2-positive early breast cancer. Design: Prospective, observational, single-group, and exploratory. This study will include 60 patients from 2 institutions in Japan and the Philippines. The invasive disease-free survival (IDFS) rates of the MRD-positive and MRD-negative groups are compared in patients with HER2-positive early breast cancer who undergo surgery after receiving NAC. Methods and analysis: Circulating tumor DNA (ctDNA) levels of patients will be evaluated 6 times: before NAC, after NAC, after surgery, and annually after surgery for 3 years. We will analyze the genetic profile of blood and tissue samples using the Todai OncoPanel (TOP) and the methylation level of DNA. The primary endpoint is IDFS. Secondary endpoints include overall survival (OS) and disease-free survival (DFS). Patient enrollment began in June 2022, and new participants are still being recruited. Ethics: This study has been approved by the National Cancer Center Hospital Certified Review Board in March 2022 and has been approved by the Research Ethics Board of the participating center. Discussion: Our findings will contribute to determining whether MRD detection using TOP is useful for predicting the recurrence of HER2-positive early breast cancer. If this is proven, MRD detected by TOP could be used in the future as a biomarker to assist in the de-/escalation of treatment strategies in the next interventional trial, thereby avoiding overtreatment in patients at low risk, and in the addition of intensive treatment modalities for those in patients at high risk.

Haploid larvae in non-mammalian vertebrates are lethal, with characteristic organ growth retardation collectively called ‘haploid syndrome’. In contrast to mammals, whose haploid intolerance is attributed to imprinting misregulation, the cellular principle of haploidy-linked defects in non-mammalian vertebrates remains unknown. Here, we investigated cellular defects that disrupt the ontogeny of gynogenetic haploid zebrafish larvae. Unlike diploid control larvae, haploid larvae manifested unscheduled cell death at the organogenesis stage, attributed to haploidy-linked p53 upregulation. Moreover, we found that haploid larvae specifically suffered the gradual aggravation of mitotic spindle monopolarization during 1–3 days post-fertilization, causing spindle assembly checkpoint-mediated mitotic arrest throughout the entire body. High-resolution imaging revealed that this mitotic defect accompanied the haploidy-linked centrosome loss occurring concomitantly with the gradual decrease in larval cell size. Either resolution of mitotic arrest or depletion of p53 partially improved organ growth in haploid larvae. Based on these results, we propose that haploidy-linked mitotic defects and cell death are parts of critical cellular causes shared among vertebrates that limit the larval growth in the haploid state, contributing to an evolutionary constraint on allowable ploidy status in the vertebrate life cycle.

Lenvatinib plus pembrolizumab (LP) therapy is currently used in patients with advanced or recurrent endometrial cancer. However, patients with uterine carcinosarcoma (UCS) were not included in the KEYNOTE-775, and the efficacy of LP therapy for patients with UCS in clinical practice remains unclear. We administered LP therapy to five patients with UCS. We aimed to report our clinical experience with LP therapy in these patients and investigate the genomic characteristics of those who responded to LP therapy.We retrospectively reviewed patients with UCS (n = 5) who underwent LP therapy at our hospital from January 2019 to December 2023. Efficacy was assessed using the response rate according to the Response Evaluation Criteria in Solid Tumors version 1.1. Safety was evaluated in terms of adverse events.The median age was 65 (55–78) years, and the mismatch repair status was proficient in all of the patients. One patient had stage II disease, and four had stage III. The median number of LP therapy courses was 8 (1–35). The overall response rate was 40%. None of the patients experienced adverse events that were grade 3 or higher. The median follow-up duration was 9 (1–26) months, median progression-free survival was 9.1 (0.16 to NA) months, and median overall survival was 10.2 (1.41 to NA) months.LP therapy may be effective for patients with UCS. As this report was based on a limited number of patients, more cases are required to investigate the efficacy of LP therapy in patients with UCS.

Abstract Background In the phase 3 EMPOWER‐Cervical 1/GOG‐3016/ENGOT‐cx9 study, cemiplimab significantly improved overall survival (OS) versus chemotherapy for patients with recurrent or metastatic cervical cancer who progressed after first‐line platinum‐based chemotherapy. We present a post hoc subgroup analysis of patients enrolled in Japan. Methods Patients were enrolled regardless of programmed cell death‐ligand 1 status and randomized 1:1 to cemiplimab 350 mg intravenously every 3 weeks or investigator's choice single‐agent chemotherapy for up to 96 weeks. Primary endpoint was OS. Key secondary endpoints were progression‐free survival (PFS) and objective response rate (ORR). Results Overall, 608 patients were randomized, of whom 56 (9.2%) were in Japan (cemiplimab, n = 29; chemotherapy, n = 27). The median (range) duration of follow‐up was 13.6 (6.0–25.3) versus 18.2 (6.0–38.2) months for patients in Japan and for the overall population, respectively. Median OS (95% confidence interval [CI]) was 8.4 (7.0‐not evaluable) and 9.4 (5.4–14.9) months for cemiplimab versus chemotherapy (hazard ratio [HR]: 0.86; 95% CI: 0.43–1.68). Median PFS (95% CI) was 4.0 (1.4–8.2) versus 3.7 (1.8–4.2) months with cemiplimab and chemotherapy (HR: 0.90; 95% CI: 0.50–1.61), respectively. ORR was 17.2% for cemiplimab and 7.4% for chemotherapy (odds ratio, 2.47; 95% CI, 0.44–13.99). Incidence of treatment‐emergent adverse events at any grade was 79.3% for cemiplimab and 100% for chemotherapy. Grade ≥3 adverse events were 37.9% versus 66.7% with cemiplimab and chemotherapy, respectively. Discussion While acknowledging limitations inherent to a small subgroup analysis, the HR of 0.86 observed in Japanese patients suggests an emerging survival benefit despite a 4.6‐month shorter median duration of follow‐up versus the overall study population.

C21H25N3O2, triclinic, P1̄ (no. 2), a = 7.6536(6) Å, b = 11.027(1) Å, c = 12.6899(11) Å, α = 66.863(2)°, β = 80.598(2)°, γ = 71.772(2)°, V = 934.38(14) Å3, Z = 2, R gt(F) = 0.0679, wR ref(F 2) = 0.1150, T = 296 K.

3D reconstruction plays an increasingly important role in modern photogrammetric systems. Conventional satellite or aerial-based remote sensing (RS) platforms can provide the necessary data sources for the 3D reconstruction of large-scale landforms and cities. Even with low-altitude Unmanned Aerial Vehicles (UAVs), 3D reconstruction in complicated situations, such as urban canyons and indoor scenes, is challenging due to frequent tracking failures between camera frames and high data collection costs. Recently, spherical images have been extensively used due to the capability of recording surrounding environments from one image. In contrast to perspective images with limited Field of View (FOV), spherical images can cover the whole scene with full horizontal and vertical FOV and facilitate camera tracking and data acquisition in these complex scenes. With the rapid evolution and extensive use of professional and consumer-grade spherical cameras, spherical images show great potential for the 3D modeling of urban and indoor scenes. Classical 3D reconstruction pipelines, however, cannot be directly used for spherical images. Besides, there exist few software packages that are designed for the 3D reconstruction from spherical images. As a result, this research provides a thorough survey of the state-of-the-art for 3D reconstruction from spherical images in terms of data acquisition, feature detection and matching, image orientation, and dense matching as well as presenting promising applications and discussing potential prospects. We anticipate that this study offers insightful clues to direct future research.

Summary: Here, we present a protocol for neonatal intracerebroventricular (ICV) delivery of adeno-associated viral vectors (AAVs), achieving gene therapy for a Rett syndrome mouse model. We describe steps for preparing mouse lines, replacing foster mothers, sex typing, and genotyping. We then detail procedures for ICV delivery and validation through immunofluorescent and immunoblot techniques. This protocol is also applicable to preclinical gene therapy research that targets the neonatal mouse brain for other neurodevelopmental disorders.For complete details on the use and execution of this protocol, please refer to Yang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Study region: The Three Gorges cascade (TGC) reservoirs, China. Study focus: Since uncertainties inherent in inflow forecasting, elevation-storage, discharge capacity, flood routing, and the preferences of decision makers (DMs) persist in the attribute measurements (AMs) and weights (AWs), problems where multiple DMs select the best compromise scheme for the long-term comprehensive operation of cascade reservoirs considering numerous attributes become a stochastic multi-attribute group decision-making (MAGDM) process. To represent uncertain AMs and AWs and consider the bounded rationality of DMs, we propose a stochastic MAGDM with integrated stochastic multicriteria acceptability analysis (SMAA) and gray cumulative prospect theory (GCPT), namely, SMAA-GCPT. After quantifying the uncertainties, SMAA-GCPT is used to model uncertain AMs and imperfect AWs with calculable probability distributions and map the sampled AMs and AWs to utility values to reflect the overall performance assuming bounded rationality. New hydrological insights for the region: Experiments on the TGC indicate that SMAA-GCPT can effectively differentiate alternative schemes and select the best compromise scheme to harmonize the conflicting benefits and risks of the TGC, with higher reliability than SMAA-2 and SMAA-GRA. The influence of uncertain AMs on the reliability of SMAA-GCPT is more obvious than that of uncertain AWs. The decision-making error risk is primarily sensitive to the inflow forecasting uncertainty, followed by the flood routing uncertainty, and is less affected by the uncertainties in elevation-storage and discharge capacity curves.

Obstacle avoidance path planning with multi-target point coverage traversal has high computational complexity and long solution time, in this paper, the problem of generating the initial obstacle avoidance coverage path is decomposed into two subproblems of covering point generation and covering point traversal path to be solved separately. For the generation of coverage points, an improved iterative self-organizing data (ISODATA) clustering algorithm is given to cluster the target points, and the center of the clustering is taken as the coverage point; for the traversal of coverage points, a probabilistic roadmap method (PRM) based on the identification of connectivity components is proposed to obtain the traversal path. For the multi-PRM (mPRM) algorithm proposed in this paper, it is compared with the multi Rapidly-exploring Random Tree (mRRT) algorithm in four different scenarios. The mPRM algorithm shows significant superiority by reducing the number of sampling points by 90% and improving the computation time by 95%, while the solution success rate reaches 100%.