circNEIL3 inhibits tumor metastasis through recruiting the E3 ubiquitin ligase Nedd4L to degrade YBX1.

Distant metastasis is a major contributor to cancer-related mortality. However, the role of circRNAs in this process remains unclear. Herein, we profiled the circRNA expression in a cohort of 68 colorectal carcinoma (CRC) primary tumors and their paired liver metastatic lesions. By overlapping with the TGFß-responsive circRNAs, circNEIL3 (hsa_circ_0001460) was identified as a TGFß-repressive and metastasis-related circRNA. Functionally, circNEIL3 effectively inhibited tumor metastasis in both and in vivo and in vivo models of various cancer types. Mechanistically, circNEIL3 exerts its metastasis-repressive function through its direct interaction with oncogenic protein, Y-box-binding protein 1 (YBX1), which consequently promotes the Nedd4L-mediated proteasomal degradation of YBX1. Importantly, circNEIL3 expression was negatively correlated to YBX1 protein level and metastatic tendency in CRC patient samples. Collectively, our findings indicate the YBX1-dependent antimetastatic function of circNEIL3 and highlight the potential of circNEIL3 as a biomarker and therapeutic option in cancer treatment.

The incidence and prevalence of recurrent corneal erosion syndrome in London, UK.

BACKGROUND: Recurrent corneal erosion syndrome (RCES) is caused by repeated episodes of corneal epithelial breakdown due to improper adherence of the corneal epithelium to the underlying basement membrane. The most common aetiologies are corneal dystrophy or previous superficial ocular trauma. The incidence and prevalence of the condition is currently unknown. This study aimed to determine the incidence and prevalence of RCES within the London population over a 5-year period in order to better inform clinicians and evaluate how this condition affects ophthalmic service provision. METHODS: A retrospective cohort study over a 5-year period reviewed 487,690 emergency room patient attendances at Moorfields Eye Hospital (MEH) London between 1 January 2015 and 31 December 2019. MEH caters for a local population comprising of around ten regional clinical commissioning groups (CCGs). The data for this study were collected using OpenEyesTM electronic medical records including demographics and comorbidities. The CCGs encompass 41% (3,689,000) of London's total 8,980,000 inhabitants. Using these data the crude incidence and prevalence rates of disease were estimated with results reported per 100,000 population. RESULTS: Out of 330,684 patients, 3623 patients were given a new diagnosis of RCES by the emergency ophthalmology services, and from these, 1056 patients attended outpatient follow-up. The crude annual incidence of RCES was estimated at 25.4 per 100,000, with a crude prevalence rate of 0.96%. There was no statistical difference in annual incidence across the 5-year period. CONCLUSIONS: The period prevalence of 0.96% shows that RCES is not uncommon. There was also a stable annual incidence over the 5-year period, showing no changing trend over the study period. However, identifying the true incidence and period prevalence is a challenging task, as minor cases may heal prior to examination by an ophthalmologist. It is highly likely that RCES is underdiagnosed and therefore underreported.

The influence of pressure injury risk on the association between left ventricular ejection fraction and all-cause mortality in patients with acute myocardial infarction 80 years or older.

BACKGROUND: We aimed to investigate whether the pressure injury risk mediates the association of left ventricular ejection fraction (LVEF) with all-cause death in patients with acute myocardial infarction (AMI) aged 80 years or older. METHODS: This retrospective cohort study included 677 patients with AMI aged 80 years or older from a tertiary-level hospital. Pressure injury risk was assessed using the Braden scale at admission, and three risk groups (low/minimal, intermediate, high) were defined according to the overall score of six different variables. LVEF was measured during the index hospitalization for AMI. All-cause death after hospital discharge was the primary outcome. RESULTS: Over a median follow-up period of 1,176 d (interquartile range [IQR], 722-1,900 d), 226 (33.4%) patients died. Multivariate Cox regression analysis showed that reduced LVEF was associated with an increased risk of all-cause death only in the high-risk group of pressure injury (adjusted hazard ratios [HR]=1.81, 95% confidence interval [CI]: 1.03-3.20; P=0.040), but not in the low/minimal- (adjusted HR=1.29, 95%CI: 0.80-2.11; P=0.299) or intermediate-risk groups (adjusted HR=1.14, 95%CI: 0.65-2.02; P=0.651). Significant interactions were detected between pressure injury risk and LVEF (adjusted P=0.003). The cubic spline with hazard ratio plot revealed a distinct shaped curve relation between LVEF and all-cause death among different pressure injury risk groups. CONCLUSIONS: In older patients with AMI, the risk of pressure injury mediated the association between LVEF and all-cause death. The classification of older patients for both therapy and prognosis assessment appears to be improved by the incorporation of pressure injury risk assessment into AMI care management.

Efficacy and safety of anastomotic leak testing in gastric cancer: a randomized controlled trial.

BACKGROUND: Anastomosis-related complications such as bleeding, leakage, and strictures, continue to be serious complications of gastric cancer surgery. Presently, these complications have yet to be reliably prevented. Here we design a comprehensive leak testing procedure which combines gastroscopy, air, and methylene blue (GAM) leak testing. We aimed to evaluated the efficacy and safety of the GAM procedure in patients with gastric cancer. METHODS: Patients aged 18-85 years without an unresectable factor as confirmed via CT were enrolled in a prospective randomized clinical trial at a tertiary referral teaching hospital and were randomly assigned to two groups: intraoperative leak testing group (IOLT) and no intraoperative leak testing group (NIOLT). The primary endpoint was the incidence of postoperative anastomosis-related complications in the two groups. RESULTS: 148 patients were initially randomly assigned to the IOLT group (n = 74) and to the NIOLT group (n = 74) between September 2018 and September 2022. After exclusions, 70 remained in the IOLT group and 68 in the NIOLT group. In the IOLT group, 5 patients (7.1%) were found to have anastomotic defects intraoperatively, which included anastomotic discontinuity, bleeding, and strictures. The NIOLT group had a higher incidence of postoperative anastomotic leakage compared to the IOLT group: 4 patients (5.8%) vs 0 patients (0%), respectively. No GAM-related complications were observed. CONCLUSION: The GAM procedure is an intraoperative leak test that can be performed safely and efficiently after a laparoscopic total gastrectomy. GAM anastomotic leak testing may effectively prevent technical defect-related anastomotic complications in patients with gastric cancer who undergo a gastrectomy. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT04292496.

Large-scale fabrication and Mo vacancy-induced robust room-temperature ferromagnetism of MoSe2 thin films.

Molybdenum selenide (MoSe2) has recently attracted particular attention due to its room-temperature ferromagnetism (RTFM) and related spintronic applications. However, not only does the FM mechanism of MoSe2 remain controversial, but also the synthesis of MoSe2 thin films with robust RTFM is still an unmet challenge. Here it is shown that using polymer-assisted deposition under appropriate growth conditions, large-scale (4 cm × 4 cm) synthesis of MoSe2 thin films with robust RTFM and a smooth surface (roughness average ∼0.22 nm) is possible. A new record-high saturation magnetization (6.69 emu g-1) is achieved in the prepared MoSe2 thin films, about 5 times the previously reported record (1.39 emu g-1) obtained in 2H-MoSe2 nanoflakes. Meanwhile, the coercivity of the MoSe2 films can be tuned down to a new record-low value (5.0 Oe), one-tenth of the previously reported record. Notably, detailed analysis combining the experimental findings and calculation results shows that the robust RTFM mainly comes from the Ruderman-Kittel-Kasuya-Yoshida (RKKY) interaction between the magnetic moments induced by abundant Mo vacancies (VMos) in the MoSe2 films. Our results give insights into the large-scale production and robust RTFM of MoSe2 thin films and may provide a platform for designing and fabricating spintronic materials and devices based on transition-metal dichalcogenides.

The association between ADAM12 gene polymorphisms and osteoarthritis: an updated meta-analysis.

BACKGROUND: Osteoarthritis of the knee is an irreversible disease that causes great pain, and genetic factors play an important role in its occurrence and development. There have been many studies on the correlation between ADAM12 polymorphisms and genetic susceptibility to osteoarthritis, but the results remain inconclusive. METHODS: Papers from PubMed, Web of Science, EMbase, Springer, SCOPUS, Google Scholar and other databases were systematically retrieved with a cut-off of January 2022. All case-control studies on ADAM12 rs3740199, rs1871054, rs1044122, and rs1278279 polymorphisms and osteoarthritis were searched. Fixed or random effects models were used for pooled analysis with OR values and 95% confidence intervals (CI), and publication bias was assessed. In addition, the false-positive reporting probability test was used to assess the confidence of a statistically significant association. RESULTS: Eleven articles were included, which included 3332 patients with osteoarthritis and 5108 healthy controls. Meta-analysis showed that the rs1871054 polymorphism of ADAM12 was associated with osteoarthritis in dominant, recessive, allelic, and homozygote genetic models [C vs. T: OR = 1.34 95% CI (1.05, 1.71), P < 0.001]. Our subgroup analysis revealed an association between the ADAM12 polymorphism rs1871054 in Asians and osteoarthritis [C vs. T: OR = 1.61, 95% CI (1.25, 2.08), P < 0.001], albeit this was only for three studies. In addition, the ADAM12 polymorphism rs1871054 is associated with osteoarthritis in patients younger than 60 years of age [C vs. T: OR = 1.39, 95% CI (1.01, 1.92), P = 0.289]; however, the ADAM12 gene rs3740199, rs1044122, and rs1278279 site polymorphisms were not significantly. Furthermore, when assessing the confidence of the positive results, the positive results were found to be credible (except for Age < 60). CONCLUSION: Polymorphism at the rs1871054 site of ADAM12 is associated with genetic susceptibility to osteoarthritis, but rs3740199, rs1044122, and rs1278279 site polymorphisms are not.

Evaluation and prediction method of railway passenger long-term vibration comfort under complex operating conditions.

Vibration contributes large increases in railway passenger discomfort during long-term sitting. Discomfort caused by vibration may differ in different operation conditions. This paper conducted field measurements to investigate the interrelationships between the three. Participants completed a 240-min train journey with their whole-body vibration, subjective comfort ratings and train operating parameters being recorded. A large correlation was observed between the estimated vibration dose value and subjective comfort. The relationship that vibration magnitude significantly increases with increasing the train speed and tunnel density was also found and quantified. A vibration exposure limit of 2.08 m/s1.75 corresponding to the boundary between subjective ratings of comfortable and discomfortable was obtained. Based on the exposure limit and the quantified relationship, a vibration comfort prediction method that can calculate the passenger's maximum tolerance time under a given operation condition was proposed and may help in determining the optimal operating speed and tunnels distribution to alleviate vibration discomfort. Practitioner summary: Similar to the guide to effect of vibration on health in current standard, a vibration exposure limit regarding comfort was provided for reference when assessing long-term vibration comfort. Meanwhile, a prediction method was proposed for determining the best train operating speed and tunnels distribution, thereby alleviating railway passengers' vibration discomfort.

Directional Transformation of Heterometallic Oxo Clusters: A New Approach to Prepare Wide-Bandgap Cathode Interlayers for Perovskite Solar Cells.

Typical wide-band gap cathode interlayer materials are difficulty in reducing interface recombination without limiting charge transport in perovskite solar cells (PSCs). Here, a lead-doped titanium-oxo cluster protected by S-containing ligands is introduced at the interface of perovskite and SnO2 . By in situ heating, the cluster is transformed into PbSO4 -PbTi3 O7 heterostructure. The oxygen atoms from sulfate ion in heterostructure connect with iodine from perovskite to boost interfacial electron extraction and reduce charge recombination. While the yielded metallic interface between PbSO4 and PbTi3 O7 promotes the electron transport across the interface. Finally, an efficiency as high as 24.2 % for the modified PSC is obtained. The heterostructure well-stabilize the interface of perovskite and SnO2 , to greatly improve the device stability. This work provides a novel strategy to prepare wide-band gap cathode interlayer by directional transformation of heterometallic oxo clusters.

PHGDH arginine methylation by PRMT1 promotes serine synthesis and represents a therapeutic vulnerability in hepatocellular carcinoma.

Serine synthesis is crucial for tumor growth and survival, but its regulatory mechanism in cancer remains elusive. Here, using integrative metabolomics and transcriptomics analyses, we show a heterogeneity between metabolite and transcript profiles. Specifically, the level of serine in hepatocellular carcinoma (HCC) tissues is increased, whereas the expression of phosphoglycerate dehydrogenase (PHGDH), the first rate-limiting enzyme in serine biosynthesis pathway, is markedly downregulated. Interestingly, the increased serine level is obtained by enhanced PHGDH catalytic activity due to protein arginine methyltransferase 1 (PRMT1)-mediated methylation of PHGDH at arginine 236. PRMT1-mediated PHGDH methylation and activation potentiates serine synthesis, ameliorates oxidative stress, and promotes HCC growth in vitro and in vivo. Furthermore, PRMT1-mediated PHGDH methylation correlates with PHGDH hyperactivation and serine accumulation in human HCC tissues, and is predictive of poor prognosis of HCC patients. Notably, blocking PHGDH methylation with a TAT-tagged nonmethylated peptide inhibits serine synthesis and restrains HCC growth in an HCC patient-derived xenograft (PDX) model and subcutaneous HCC cell-derived xenograft model. Overall, our findings reveal a regulatory mechanism of PHGDH activity and serine synthesis, and suggest PHGDH methylation as a potential therapeutic vulnerability in HCC.

Is lymphatic invasion of microrectal neuroendocrine tumors an incidental event?: A case report.

BACKGROUND: A rectal neuroendocrine tumor (rNET) is a malignant tumor originating from neuroendocrine cells. Currently, tumor size is the primary basis for assessing tumor risk. CASE SUMMARY: This article reports the case of a 46-year-old male patient who underwent a colonoscopy that found a 3 mm rectal polypoid bulge. The pathological examination of a sample collected with biopsy forceps revealed a neuroendocrine tumor. Further endoscopic submucosal dissection rescue therapy was used. The presence of lymphatic vessels indicated that the tumor had infiltrated the negative resection margin. The lesion was located in the distal rectum near the anal canal. Therefore, to ensure the patient's quality of life, follow-up observation was conducted after full communication with the patient. No tumor recurrence or distant metastasis has been found during the 13-mo follow-up after surgery. CONCLUSION: Despite the presence of lymphatic invasion and extremely small diameter rNETs in our case, this phenomenon may not imply a higher risk of distant lymph node and organ metastasis.

Collaborative Passivation for Dual Charge Transporting Layers Based on 4-(chloromethyl)benzonitrile Additive toward Efficient and Stable Inverted Perovskite Solar Cells.

Poor carrier transport capacity and numerous surface defects of charge transporting layers (CTLs), coupled with misalignment of energy levels between perovskites and CTLs, impact photoelectric conversion efficiency (PCE) of inverted perovskite solar cells (PSCs) profoundly. Herein, a collaborative passivation strategy is proposed based on 4-(chloromethyl) benzonitrile (CBN) as a solution additive for fabrication of both [6,6]-phenyl-C61-butyric acid methylester (PCBM) and poly(triarylamine) (PTAA) CTLs. This additive can improve wettability of PTAA and reduce the agglomeration of PCBM particles, which enhance the PCE and device stability of the PSCs. As a result, a PCE exceeding 20% with a remarkable short circuit current of 23.9 mA cm-2 , and an improved fill factor of 81% is obtained for the CBN- modified inverted PSCs. Devices maintain 80% and 70% of the initial PCE after storage under 30% and 85% humidity ambient conditions for 1000 h without encapsulation, as well as negligible light state PCE loss. This strategy demonstrates feasibility of the additive engineering to improve interfacial contact between the CTLs and perovskites for fabrication of efficient and stable inverted PSCs.

A Novel Tri-Functionality pH-Magnetic-Photocatalytic Hybrid Organic-Inorganic Polyoxometalates Augmented Microspheres for Polluted Water Treatment.

The severe water pollution from effluent dyes threatens human health. This study created pH-magnetic-photocatalytic polymer microspheres to conveniently separate the photocatalyst nanoparticles from the treated water by applying an external magnetic field. While fabricating magnetic nanoparticles' (MNPs) microspheres, incorporating 0.5 wt.% iron oxide (Fe3O4) showed the best magnetophoretic separation ability, as all the MNPs microspheres were attracted toward the external magnet. Subsequently, hybrid organic-inorganic polyoxometalates (HPOM), a self-synthesized photocatalyst, were linked with the functionalized magnetic nanoparticles (f-MNPs) to prepare augmented magnetic-photocatalytic microspheres. The photodegradation dye removal efficiency of the augmented magnetic-photocatalytic microspheres (f-MNPs-HPOM) was then compared with that of the commercial titanium dioxide (TiO2) photocatalyst (f-MNPs-TiO2). Results showed that f-MNPs-HPOM microspheres with 74 ± 0.7% photocatalytic removal efficiency better degraded methylene orange (MO) than f-MNPs-TiO2 (70 ± 0.8%) at an unadjusted pH under UV-light irradiation for 90 min. The excellent performance was mainly attributed to the lower band-gap energy of HPOM (2.65 eV), which required lower energy to be photoactivated under UV light. The f-MNPs-HPOM microspheres demonstrated excellent reusability and stability in the photo-decolorization of MO, as the microspheres retained nearly the same removal percentage throughout the three continuous cycles. The degradation rate was also found to follow the pseudo-first-order kinetics. Furthermore, f-MNPs-HPOM microspheres were pH-responsive in the photodegradation of MO and methylene blue (MB) at pH 3 (acidic) and pH 9 (alkaline). Overall, it was demonstrated that using HPOM photocatalysts in the preparation of magnetic-photocatalytic microspheres resulted in better dye degradation than TiO2 photocatalysts.

BET proteins: Biological functions and therapeutic interventions.

Bromodomain and extra-terminal (BET) family member proteins (BRD2, BRD3, BRD4 and BRDT) play a pivotal role in interpreting the epigenetic information of histone Kac modification, thus controlling gene expression, remodeling chromatin structures and avoid replicative stress-induced DNA damages. Abnormal activation of BET proteins is tightly correlated to various human diseases, including cancer. Therefore, BET bromodomain inhibitors (BBIs) were considered as promising therapeutics to treat BET-related diseases, raising >70 clinical trials in the past decades. Despite preliminary effects achieved, drug resistance and adverse events represent two major challenges for current BBIs development. In this review, we will introduce the biological functions of BET proteins in both physiological and pathological conditions; and summarize the progress in current BBI drug development. Moreover, we will also discuss the major challenges in the front of BET inhibitor development and provide rational strategies to overcome these obstacles.

Hsa_circ_0005273 acts as a sponge of miR-509-3p to promote the malignant behaviors of breast cancer by regulating HMMR expression.

BACKGROUND: Breast cancer (BC) is a common malignant tumor that threatens the health of women worldwide. Hsa_circ_0005273 has been identified as a carcinogenic factor in some solid tumors, including BC. However, the molecular mechanism of circ_0005273 in BC is poorly defined. METHODS: The expression of circ_0005273, miR-509-3p, and hyaluronan-mediated motility receptor (HMMR) mRNA in BC was detected by quantitative real-time polymerase chain reaction. Cell proliferation, migration, invasion, and apoptosis were detected by 5-ethynyl-2'-deoxyuridine, transwell, and flow cytometry assays. The glycolysis level was detected via specific kits. Western blot was used to detect protein expression. Binding between miR-509-3p and circ_0005273 or HMMR was also verified by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation assays. Xenograft tumor model was used to detect tumor changes in mice, and immunohistochemistry assay was employed to detect Ki-67 abundance. RESULTS: Circ_0005273 was increased in BC tissues and cells. Circ_0005273 knockdown might inhibit BC cell proliferation, migration, invasion, glutamine metabolism, and induce apoptosis. Circ_0005273 was a miR-509-3p, and the repression role of circ_0005273 absence on BC cell development was weakened by miR-509-3p inhibitor or HMMR overexpression. Circ_0005273 up-regulated the expression of HMMR by sponging miR-509-3p. Additionally, circ_0005273 silencing might hinder tumor growth in vivo. CONCLUSION: Circ_0005273 knockdown might repress BC cell malignant behaviors by regulating the miR-509-3p/HMMR axis, which might provide a potential therapeutic target for BC.

[Tiaoshen Jieyu acupuncture combined with sertraline hydrochloride tablet for post-stoke depression: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy between Tiaoshen Jieyu acupuncture (acupuncture for regulating mind and relieving depression) combined with sertraline hydrochloride tablet and simple sertraline hydrochloride tablet for post-stroke depression (PSD). METHODS: A total of 76 patients with PSD were randomized into an observation group (38 cases, 6 cases dropped off) and a control group (38 cases, 4 cases dropped off). Both groups were treated with conventional treatment i.e. controlling blood pressure and anti-inflammation. Sertraline hydrochloride tablet was given orally in the control group, 20 mg a time, once a day. On the basis of the treatment in the control group, Tiaoshen Jieyu acupuncture was applied at Baihui (GV 20), Yintang (GV 24+), Neiguan (PC 6), Taichong (LR 3), etc. in the observation group, Baihui (GV 20) and Yintang (GV 24+) were connected to electroacupuncture, with disperse-dense wave, 2 Hz/100 Hz in frequency, 30 min a time, once a day, 6 times a week. Treatment of 8 weeks was required in both groups. Before and after treatment, the scores of Hamilton depression scale (HAMD), National Institutes of Health stroke scale (NIHSS), Barthel index (BI) and Pittsburgh sleep quality index (PSQI) were observed respectively, the therapeutic efficacy and rate of adverse reactions were evaluated in the two groups. RESULTS: After treatment, the scores of HAMD, NIHSS and PSQI were lower while BI scores were higher than those before treatment in both groups (P<0.05); the scores of HAMD, NIHSS and PSQI in the observation group were lower while BI score was higher than those in the control group (P<0.05). The total effective rate was 93.8% (30/32) in the observation group, which was higher than 70.6% (24/34) in the control group (P<0.05). The rate of adverse reactions was 9.4% (3/32) in the observation group, which was lower than 32.4% (11/34) in the control group (P<0.05). CONCLUSION: Tiaoshen Jieyu acupuncture combined with sertraline hydrochloride tablet can improve the depression degree, neurological function, activity of daily living and sleep quality in patients with post-stroke depression, the clinical efficacy is superior to simple sertraline hydrochloride, and can alleviate the adverse reactions caused by medication.

Sulfonated magnetic multi-walled carbon nanotubes with enhanced bonding stability, high adsorption performance, and reusability for water remediation.

In view of the simple and rapid conveniency of magnetic separation, magnetic nanocomposites had notably gained attention from researchers for environmental field applications. In this work, carboxylated magnetic multi-walled carbon nanotubes (c-MMWCNTs) and novel sulfonated MMWCNTs (s-MMWCNTs) were synthesized by a facile solvent-free direct doping method. Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscope, energy dispersive X-ray, vibrating sample magnetometer, and point of zero charge analyses confirmed the successful doping of the Fe3O4 nanoparticles into the functionalized MWCNTs to form MMWCNTs. Besides, the bonding stabilities of both c-MMWCNTs and s-MMWCNTs were compared, and results showed that s-MMWCNTs possessed more substantial bonding stability than that of c-MMWCNTs with significantly less leaching amount of Fe3O4. The adsorption capacity of s-MMWCNTs was higher than that of c-MMWCNTs owing to the stronger electronegativity sulfonic group in s-MMWCNTs. Moreover, the reusability experiments proved that the adsorbent remained consistently excellent MB removal efficiency (R > 94%) even reused for twelve cycles of batch adsorption. The finding of the present work highlights the simple fabrication of novel s-MMWCNTs and its potential to be served as a promising and sustainable adsorbent for water remediation owing to its enhanced bonding stability, high adsorption performance, magnetic separability, and supreme recyclability.

Operational reliability of urban drainage systems under uncertainties.

Water quality risks from overflows have attracted significant research attention, and the reliability of urban drainage systems (UDS) is in urgent need of assessment and improvement. The overflow volume and concentration of critical pollutants are generally used as assessment indicators, which is quite time consuming and cumbersome especially under continuous rainfall. Simplifying the water quality risk assessment indicators for the UDS reliability is intractable. For this purpose, this study proposes the detention tank emptying time as a new reliability evaluation indicator, which greatly reduces the calculation burden by converting water quality risk into hydraulic risk. On this basis, the effects of rainfall, dry weather flow (DWF), actuators and their interactions on reliability are quantified by massive scenarios. It shows that the DWF affects the emptying process via weekly and daily seasonality and its interaction with rainfall is mainly responsible for unreliability. Further, the engineering facility linkage controlled by the actuator to cope with the interaction is the key. Particularly, the Prophet algorithm is innovatively applied to mine the patterns and generate the DWF series for the challenge of sparse DWF data. In conclusion, the indicator proposed expands the connotation of UDS reliability assessment, prompting a small investment in replacing actuators with better controllability and greatly improving reliability. It guides the engineering planning and enhancement from a new perspective of whole-chain optimization from the global to the detailed level.