WRN helicase is a synthetic lethal target in microsatellite unstable cancers.

Synthetic lethality-an interaction between two genetic events through which the co-occurrence of these two genetic events leads to cell death, but each event alone does not-can be exploited for cancer therapeutics1. DNA repair processes represent attractive synthetic lethal targets, because many cancers exhibit an impairment of a DNA repair pathway, which can lead to dependence on specific repair proteins2. The success of poly(ADP-ribose) polymerase 1 (PARP-1) inhibitors in cancers with deficiencies in homologous recombination highlights the potential of this approach3. Hypothesizing that other DNA repair defects would give rise to synthetic lethal relationships, we queried dependencies in cancers with microsatellite instability (MSI), which results from deficient DNA mismatch repair. Here we analysed data from large-scale silencing screens using CRISPR-Cas9-mediated knockout and RNA interference, and found that the RecQ DNA helicase WRN was selectively essential in MSI models in vitro and in vivo, yet dispensable in models of cancers that are microsatellite stable. Depletion of WRN induced double-stranded DNA breaks and promoted apoptosis and cell cycle arrest selectively in MSI models. MSI cancer models required the helicase activity of WRN, but not its exonuclease activity. These findings show that WRN is a synthetic lethal vulnerability and promising drug target for MSI cancers.

Artificial LiF-Rich Interface Enabled by In situ Electrochemical Fluorination for Stable Lithium-Metal Batteries.

Lithium (Li)-metal batteries are promising next-generation energy storage systems. One drawback of uncontrollable electrolyte degradation is the ability to form a fragile and nonuniform solid electrolyte interface (SEI). In this study, we propose the use of a fluorinated carbon nanotube (CNT) macrofilm (CMF) on Li metal as a hybrid anode, which can regulate the redox state at the anode/electrolyte interface. Due to the favorable reaction energy between the plated Li and fluorinated CNTs, the metal can be fluorinated directly to a LiF-rich SEI during the charging process, leading to a high Young's modulus (~2.0 GPa) and fast ionic transfer (~2.59×10-7  S cm-1 ). The obtained SEI can guide the homogeneous plating/stripping of Li during electrochemical processes while suppressing dendrite growth. In particular, the hybrid of endowed full cells with substantially enhanced cyclability allows for high capacity retention (~99.3 %) and remarkable rate capacity. This work can extend fluorination technology into a platform to control artificial SEI formation in Li-metal batteries, increasing the stability and long-term performance of the resulting material.

ZIC2 is downregulated and represses tumor growth via the regulation of STAT3 in breast cancer.

Although early detection and systemic therapies have improved the diagnosis and clinical cure rate of breast cancer, breast cancer remains the most frequently occurring malignant cancer in women due to a lack of sufficiently effective treatments. Thus, to develop potential targeted therapies and thus benefit more patients, it is helpful to understand how cancer cells work. ZIC family members have been shown to play important roles in neural development and carcinogenesis. In our study, we found that ZIC2 is downregulated in breast cancer tissues at both the mRNA and protein levels. Low expression of ZIC2 was correlated with poor outcome in breast cancer patients and serves as an independent prognostic marker. Furthermore, overexpression of ZIC2 repressed, whereas knockdown of ZIC2 promoted, cell proliferation and colony formation ability in vitro and tumor growth in vivo. Using ChIP-seq and RNA-seq analysis, we screened and identified STAT3 as a potential target for ZIC2. ZIC2 bound to the STAT3 promoter and repressed the promoter activities of STAT3. ZIC2 knockdown induced the expression of STAT3, increasing the level of phosphorylated STAT3. These results suggest that ZIC2 regulates the transcription of STAT3 by directly binding to the STAT3 promoter. Additionally, interfering STAT3 with siRNAs or inhibitors abrogated the oncogenic effects induced by decreased ZIC2. Taken together, our results indicate that ZIC2 serves as a useful prognostic marker in breast cancer and acts as a tumor suppressor by regulating STAT3, implying that STAT3 inhibitors might provide an alternative treatment option for breast cancer patients with ZIC2 downregulation.

Potential influence of COVID-19/ACE2 on the female reproductive system.

The 2019 novel coronavirus (2019-nCoV) appeared in December 2019 and then spread throughout the world rapidly. The virus invades the target cell by binding to angiotensin-converting enzyme (ACE) 2 and modulates the expression of ACE2 in host cells. ACE2, a pivotal component of the renin-angiotensin system, exerts its physiological functions by modulating the levels of angiotensin II (Ang II) and Ang-(1-7). We reviewed the literature that reported the distribution and function of ACE2 in the female reproductive system, hoping to clarify the potential harm of 2019-nCoV to female fertility. The available evidence suggests that ACE2 is widely expressed in the ovary, uterus, vagina and placenta. Therefore, we believe that apart from droplets and contact transmission, the possibility of mother-to-child and sexual transmission also exists. Ang II, ACE2 and Ang-(1-7) regulate follicle development and ovulation, modulate luteal angiogenesis and degeneration, and also influence the regular changes in endometrial tissue and embryo development. Taking these functions into account, 2019-nCoV may disturb the female reproductive functions through regulating ACE2.

Gimmicks of gamma-aminobutyric acid (GABA) in pancreatic ß-cell regeneration through transdifferentiation of pancreatic α- to ß-cells.

In vivo regeneration of lost or dysfunctional islet ß cells can fulfill the promise of improved therapy for diabetic patients. To achieve this, many mitogenic factors have been attempted, including gamma-aminobutyric acid (GABA). GABA remarkably affects pancreatic islet cells' (α cells and ß cells) function through paracrine and/or autocrine binding to its membrane receptors on these cells. GABA has also been studied for promoting the transformation of α cells to ß cells. Nonetheless, the gimmickry of GABA-induced α-cell transformation to ß cells has two different perspectives. On the one hand, GABA was found to induce α-cell transformation to ß cells in vivo and insulin-secreting ß-like cells in vitro. On the other hand, GABA treatment showed that it has no α- to ß-cell transformation response. Here, we will summarize the physiological effects of GABA on pancreatic islet ß cells with an emphasis on its regenerative effects for transdifferentiation of islet α cells to ß cells. We will also critically discuss the controversial results about GABA-mediated transdifferentiation of α cells to ß cells.

Acute Massive Pulmonary Thromboembolism Treated by Selective Catheter-Directed Thrombolysis.

BACKGROUND: To evaluate the safety and efficacy of selective catheter-directed thrombolysis (SCDT) in treating acute massive pulmonary thromboembolism (AMPTE). METHODS: Twenty-six AMPTE patients were enrolled between March 2010 and March 2013. A Uni*Fuse infusion system was inserted into the main pulmonary artery thrombus. The thrombolytic regimen included an intraoperative bolus injection of 250,000 IU urokinase, followed by continuous thrombolytic infusion of 5,000 IU/kg per (every) 24 hr urokinase for 72 hr postoperatively. Clinical symptoms, shock index (SI), systolic pulmonary artery pressure (sPAP), peripheral arterial partial pressure of oxygen (PaO2), and Miller index (MI) were assessed before and after treatment. RESULTS: The patients included 16 men and 10 women (49.9 ± 18.8 years old; time to onset of 50.2 ± 28.5 hr). After thrombolysis, dyspnea and cough were relieved to varying degrees; chest pain, hemoptysis, and syncope disappeared. Importantly, a clinical success rate of 100% was achieved. All objective indices were improved: SI decreased from 1.74 ± 0.38 before operation to 0.71 ± 0.09 postoperatively (P = 0.00); PaO2 increased from 52.78 ± 6.92 mm Hg to 85.98 ± 5.91 mm Hg (P = 0.00); sPAP was reduced from 65.19 ± 8.22 mm Hg to 34.42 ± 4.05 mm Hg (P = 0.00); MI dropped from 0.69 ± 0.09 to 0.33 ± 0.06 (P = 0.00). Mean total urokinase amounts were 1,298,000 IU for each patient. Postoperative complications included 2 cases of puncture-site hematoma (cured by pressure bandage) and 1 case of gastrointestinal hemorrhage (healed by conservative treatment without blood transfusion). CONCLUSIONS: SCDT may be considered a safe and efficacious treatment for AMPTE.

Translation and psychometric evaluation of the Chinese version of functional digestive disorders quality of life questionnaire.

BACKGROUND: Few useful patient-reported outcomes scales for functional dyspepsia exist in China. AIMS: The purpose of this work was to translate and cross-culturally adapt the Functional Digestive Disorders Quality of Life Questionnaire (FDDQL) from the English version to Chinese (in Mandarin). METHODS: The following steps were performed: forward translations, synthesis of the translations, backward translations, pre-testing and field testing of FDDQL. Reliability, validity, responsiveness, confirmatory factor analysis, item response theory and differential item functioning of the scale were analyzed. RESULTS: A total of 300 functional dyspepsia patients and 100 healthy people were included. The total Cronbach's alpha was 0.932, and split-half reliability coefficient was 0.823 with all test-retest coefficients greater than 0.9 except Coping With Disease domain. In construct validity analysis, every item correlated higher with its own domain than others. The comparative fit index of FDDQL was 0.902 and root mean square error of approximation was 0.076. Functional dyspepsia patients and healthy people had significant differences in all domains. After treatment, all domains had significant improvements except diet. Item response theory analysis showed the Person separation index of 0.920 and the threshold estimator of items was normally distributed with a mean of 0 and standard deviation of 1.27. The residuals of each item were between -2.5 and 2.5, without statistical significance. Differential item functioning analysis found that items had neither uniform nor non-uniform differential item functioning in different genders and age groups. CONCLUSIONS: The Chinese version of FDDQL has good psychometric properties and is suitable for measuring the health status of Chinese patients with functional dyspepsia.

Treatment of suprarenal abdominal aortic stump rupture using a modified stent graft.

Suprarenal abdominal aortic rupture cannot be repaired using a conventional covered stent without branches because it is necessary to reconstruct the visceral arteries. Traditional open aortic repair is associated with relatively high perioperative mortality and morbidity rates. We present a patient with a history of thoracoabdominal aortic pseudoaneurysm that had been treated with bypass grafting from the thoracic aorta to the left common iliac artery 5 months earlier. The patient presented with rupture of the suprarenal abdominal aortic stump. He was successfully treated by placement of a modified stent graft using a hybrid technique, which decreased the difficulty of operation and avoided serious postoperative complications. This hybrid method, which has not previously been reported, highlights the usefulness of vascular surgeons having experience in both open and endovascular techniques.

Spatial distribution, influencing factors and innovative development countermeasures of farmer cooperatives in Hunan Province, China.

China's rural reform is reliant on farmers' cooperatives as a key organization vehicle. It plays an important role in promoting rural revitalization. Such as, realizing the organic connection between small farmers and agricultural modernization. This study used the nearest neighbor index and kernel density estimation to analyze the spatial distribution and structural characteristics of farmer cooperatives in Hunan Province. It revealed the spatial differentiation law of cooperatives. Also using geographical detectors to figure out the main factors that affect the spatial distribution. The results show that: ① Hunan Farmers Cooperatives show significant spatial agglomeration. The overall spatial distribution shows the spatial characteristics of "one core, one circle, and multiple points". And the spatial distribution pattern of "large agglomeration, finger-shaped radiation distribution". Among them, the distribution of provincial demonstration cooperatives is relatively balanced. ② Cooperatives in six types of industries, such as planting, forestry, and feeding, showed agglomeration distribution. Different industrial cooperatives spread out in different ways, such as in an anti-"L" shape, a dual-core shape, or a one-center area. ③ The 24 influence factors selected from the five dimensions of the natural environment, social economic basis, production basis, output capacity, and facility basis have high, general, and weak influence on cooperatives' spatial distribution. The development and distribution of cooperatives mainly depend on resource endowment, social and economic development level, and market dependence. The spatial distribution heterogeneity of different professional cooperatives is mainly affected by slope, per capita disposable income of rural residents, road density, and other factors. ④ The progression of farmer cooperatives in Hunan Province should prioritize high-quality development, emphasizing the need for innovative approaches and transformative strategies within rural industrial organizations. It is imperative to optimize the spatial distribution of cooperatives, strategically contributing to the establishment of a novel framework for modern agricultural development in Hunan Province. Additionally, there is a critical emphasis on spearheading collaborative initiatives among cooperatives of varied industrial types, aimed at fostering the integrated development of rural primary, secondary, and tertiary industries.

Experimental Study on the Diffusion Law of Coal-Based Solid Waste Slurry with Grouting Filling in the Gangue Voids of the Caving Zone.

Due to the concealment of the caving zone, it is difficult to detect and grasp the diffusion law of the slurry in the voids of the gangue pile. On the preparation of reasonable grouting filling materials, a large-scale three-dimensional gangue grouting filling test system has been established to detect the slurry pressure and resistivity inside the gangue pile and analyze the flow pattern of the slurry in the voids of the gangue pile. The research results show that the slump and bleeding rate of the filling slurry are significantly reduced with the increase of the fly ash content. The optimal ratio of fly ash, coal gangue, and gasification slag is 7:2:1, with a mass fraction of 72%. In the process of grouting, the internal pressure of the gangue pile can be divided into the initial stable stage, the step growth stage, and the pressure stability stage, and the change curve of the pressure sensor at the lower level is similar. The resistance value of the original broken gangue in the experiment is approximately 1600 Ω. Grouting filling forms a slurry-rock mixture, and its resistance continuously decreases with the stable injection of the slurry (minimum value 150 Ω). It is determined that the slurry near the grouting hole mainly diffuses longitudinally with a good void filling effect. The void channels of slurry diffusion are randomly distributed and have different shapes, which hinder slurry flow and diffusion. Slurry particles accumulate and settle at local small voids. Meanwhile, the surface of the gangue blocks is dry, and the slurry absorbs part of the water during diffusion, resulting in the increase of the slurry concentration and the weakening of the lateral diffusion ability. Secondary or multiple grouting can effectively fill the void of the broken gangue and further improve the filling effect.

Prognostic Nutritional Index Enhances the Discriminatory Ability of Procalcitonin for Predicting Pediatric Sepsis.

Objective. Improving diagnostic ability of pediatric sepsis is of great significance for reducing the mortality of sepsis. This study explored the discriminatory capacity of nutritional index (PNI) in pediatric sepsis. Methods. We retrospectively enrolled 134 children with suspected sepsis and collected their clinical and laboratory data. Receiver operating characteristic curves (ROC), decision curve analysis (DCA) and net reclassification improvement (NRI) were performed to compare the predictive significance of the PNI, procalcitonin (PCT) and their combination. Results. Among 134 patients, 65 children were diagnosed with sepsis and 69 children with non-sepsis. PCT and PNI were independently associated with pediatric sepsis. PCT was superior to PNI to predict pediatric sepsis. The model based on PCT + PNI improved the predictive capacity than them alone, as demonstrated by ROC, DCA and NRI, respectively. Conclusion. PNI was independently associated with pediatric sepsis, and addition of PNI could improve the capacity of PCT to predict pediatric sepsis.

Downregulation of KLF8 expression by shRNA induces inhibition of cell proliferation in CAL27 human oral cancer cells.

OBJECTIVES: KLF8 is a member of KLF transcription factors which play an important tolr in oncogenesis. It is barely expressed in normal human epithelial cells but highly overexpressed in several types of human cancer cell lines. In the present study, we investigate the role of KLF8 in oral cancer and the effects of KLF8 knockdown via lentivirus mediated siRNA infection in human adenosquamos carcinoma CAL 27 cells. STUDY DESIGN: We developed a vector-based siRNA expression system that can induce RNAi in CAL 27 oral cancer cells. Downregulation of KLF8 was confirmed by evaluating GFP expressions, RT-PCR and western blot analysis. Finally, the effects of KLF8 downregulation were analyzed by MTT assay and colony formation assays. RESULTS: The expression levels of KLF8 mRNA and proteins are reduced in CAL 27 cells that transfected with 21-nt siRNA against KLF8. Lentivirus-mediated silencing of KLF8 reduces cell proliferation and colonies number, thereby indicating the role of KLF8 in cell proliferation and tumorigenesis. CONCLUSIONS: These results strongly suggest that KLF8 is essential for growth of CAL 27 cancer cells. A better understanding of KLF8 function and processing may provide novel insights into the clinical therapy of oral cancer.

Evaluation of Fourier transform infrared (FTIR) spectroscopy with multivariate analysis as a novel diagnostic tool for lymph node metastasis in gastric cancer.

Fourier transform infrared (FTIR) spectroscopy is a vibration spectroscopy that uses infrared radiation to vibrate to absorb the molecular bonds in its absorbed sample. The main purpose of this study was to evaluate FTIR spectroscopy as a novel diagnostic tool for lymph node metastasis (LNM) of gastric cancer. We collected 160 fresh non-metastatic and metastatic lymph nodes (80 each) from 60 patients with gastric cancer for spectral analysis. FTIR spectra of lymph node (LN) samples were obtained in the wavenumber range of 4000 cm-1 to 900 cm-1. We calculated the changes in the ratio of spectral intensity (/ I1460). Principal component analysis (PCA) and Fisher's discriminant analysis (FDA) were used to distinguish malignant from normal LN. Four significant bands at 1080 cm-1, 1640 cm-1, 1740 cm-1 and 3260 cm-1 separated metastatic and non-metastatic LN spectra into two distinct groups by PCA.T-tests showed that, along with the relative intensity ratios (I1080/I1460, I1640/I1460, I3260/I1460, I1740/I1460), these band ratios were also able to differentiate between malignant and benign LN spectra. Six parameters (P1080 cm-1, P1300 cm-1, I1080/I1460, I1640/I1460, I3260/I1460, I1740/I1460) were selected as independent factors to set up discriminant functions. The sensitivity of FTIR spectroscopy in diagnosing LNM was 95 % by discriminant analysis. Our study suggested that FTIR spectroscopy can be a useful tool to examine LNM with high sensitivity and specificity for LNM diagnosis. Therefore it can be used in clinical practice as a non-invasive method.

Regulatory mechanisms of the cAMP-responsive element binding protein 3 (CREB3) family in cancers.

The CREB3 family of proteins, encompassing CREB3 and its four homologs (CREB3L1, CREB3L2, CREB3L3, and CREB3L4), exerts pivotal control over cellular protein metabolism in response to unfolded protein reactions. Under conditions of endoplasmic reticulum stress, activation of the CREB3 family occurs through regulated intramembrane proteolysis within the endoplasmic reticulum membrane. Perturbations in the function and expression of the CREB3 family have been closely associated with the development of diverse diseases, with a particular emphasis on cancer. Recent investigations have shed light on the indispensable role played by CREB3 family members in modulating the onset and progression of various human cancers. This comprehensive review endeavors to provide an in-depth examination of the involvement of CREB3 family members in distinct human cancer types, accentuating their significance in the pathogenesis of cancer and the manifestation of malignant phenotypes.

Endoscopy-assisted cerebral falx incision via unilateral approach in treatment of dissymmetric bilateral frontal contusion.

BACKGROUND: Dissymmetric bilateral frontal contusion (DBFC) is relatively frequent in the clinic. In this study, we aimed to investigate the development tendency, clinical features, and treatment experience of DBFC and to summarize out experience in treating these patients via minimally invasive means-endoscopy. METHODS: Over the past 3 years, we have treated a total of 31 patients with DBFC using endoscopy-assisted unilateral cerebral falx incision. We used a 30-degree endoscope to observe the involvement of brain contusion and whether the brain contusions have been cleaned thoroughly. Another 30 patients treated by routine bilateral approach within the same period were taken as controls. RESULTS: Seventeen cases (54.8%) in the unilateral-operation group survived and were in good condition, 8 cases (25.8%) had moderate disability, and 4 cases (12.9%) had severe disability; 1 case (3.2%) was in vegetable state, and 1 case (3.2%) died. Compared with the control group, the GOS score was not significantly different in the unilateral-operation group, but the operation time, blood transfusion volume, length of hospital stay, incidence of mental disorder, and incidence of olfactory nerve injury were greatly reduced in the unilateral-operation group. CONCLUSIONS: Endoscopy-assisted unilateral cerebral falx incision can shorten the operation time and reduce surgical trauma and complications when used for treatment of patients with DBFC.

Innovative Design of Intelligent Health Equipment for Helping the Blind in Smart City.

The rapid advancement of information technology in today's modern society is contributing to an increase in the general degree of civilization in society. People are pleased with technological progress, but they are also becoming more aware that a major challenge confronting the advancement of social civilization at the moment is determining how to alleviate the difficulties associated with traveling and participating in social activities for the blind, as well as increasing the frequency with which they go out, travel, and participate in other activities. The blindness equipment that is now accessible in China is no longer suitable to meet the needs of blind people, but the growth of smart cities offers an opportunity to change this. Guide devices are crucial among the numerous types of equipment to assist the blind, and in order to better fulfill their various demands, we must upgrade and optimize the existing devices. The Chinese People's Daily highlights some of the key barriers to blind people's access in its 2019 article: random parking that blocks blind lanes; and "snake" and "broken" blind lanes that are not created with blind people's access in mind. In a smart city, accurate placement via smart maps helps alleviate a number of traffic-related issues for blind individuals. In this paper, we propose an intelligent guide device and interactive software to provide a more intelligent way for blind people to travel, which can effectively improve blind people's traffic conditions and make their travel easy, convenient, and safe, reflecting society's concern for blind people.

3D printing calcium alginate adsorbents for highly efficient recovery of U(VI) in acidic conditions.

In this study, a three-dimensional (3D) porous calcium alginate (3D CA) scaffold was successfully constructed using a direct-ink-writing-based 3D printing method combined with an in-situ calcium ion cross-linking procedure. The 3D CA contained orderly aligned microstructures with excellent structural robustness and an abundant number of active binding sites. The adsorption experiments verified that 3D CA had a considerably wide pH value (3-10) serving range, but also delivered a significantly higher adsorption capacity for U(VI) (117.3 mg/g at pH = 2.5) under acidic conditions, compared to other previously reported alginate-based porous adsorbents. The adsorption mechanisms originated from the synergistic effect of electrostatic interactions and ion exchange. The 3D CA eluted the adsorbed U(VI) in a strong acid solution through protonation mechanism, facilitating the continued enrichment and recycling of U(VI). In addition, the 3D CA demonstrated good microstructure stability and absorption capacity stability when it was immersed in hydrochloric acid solutions at different concentrations (3.6 × 10-3 to 2 mol/L) for 24 h. Therefore, the 3D CA could be used for the removal and recycling of U(VI) from acidic solutions beyond its wide pH working range, due to its stronger acid stability and higher U(VI) adsorption capacity.

CdS and Ag synergistically improved the performance of g-C3N4 on visible-light photocatalytic degradation of pollution.

CdS-AgO@g-C3N4 nanocomposites were successfully synthesized and characterized by XRD, N2 physical adsorption, XPS, SEM, TEM, EDX, and UV-Vis DRS (various technical means). The adsorption light range of as-prepared materials could extend to the whole visible light region with the addition of Ag. Silver can act as a bridge to facilitate the separation of electrons and holes, thereby greatly enhancing the photocatalytic activity of CdS-AgO@g-C3N4, enabling the maximum degradation efficiency of salicylic acid in water to reach 92.8% under visible light. Peroxy radical is the most important radical in the photocatalytic reaction process, followed by electron and hole, while hydroxyl radical has almost no effect. In addition, the mechanism of photocatalytic process was also explored.