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In this study, the flexural performance of the steel fiber reinforced concrete beams with recycled fine and coarse aggregates was investigated through the experiments. The effects of steel fiber volume fraction, recycled fine and coarse aggregate replacement ratio, and concrete compressive strength grade on the flexural performance of steel fiber reinforced recycled aggregate concrete (SFRAC) beams were systematically studied in terms of failure mode, flexural capacity, cracking patterns, load-deflection response, and load-tensile reinforcement strain response. The results showed that the flexural capacity and deflection of beams increased and decreased with the increase of steel fiber volume fraction, respectively. The beam with 100% replacement ratio of recycled fine aggregate and 0.5% volume fraction of steel fiber presented the similar or even better flexural performance than that of the ordinary concrete beam. By adding 1.0% volume fraction of steel fiber, the flexural capacity of beam with both 100% replacement ratio of recycled fine and coarse aggregates was higher than that of the ordinary concrete beam. Based on the experimental results of SFRAC beams in this study and other literature, the effects of steel fiber volume fraction and recycled aggregate replacement ratio on the flexural capacity of beams were quantitatively analyzed. Lastly, a model for the prediction of SFRAC beam flexural capacity was proposed and verified.

To describe a novel modification of technique to improve efficacy of robot-assisted laparoscopic extravesical ureteral reimplantation (RALUR-EV) in infants.Between April 2017 and July 2019, sixteen infants with primary obstructive megaureter (POM) (Age range: 4-12 months) underwent robot-assisted ureteral reimplantation were reviewed in this series. In addition to the conventional Lich-Gregoir technique, the detrusor tunnel has been extended to the mobilized anterior bladder wall to guarantee sufficient tunnel length/ureter diameter ratio and avoid ureteral angulation. All patients underwent repeated ultrasound, diuretic renal dynamic imaging and voiding cystourethrography (VCUG) perioperatively and the outcomes were documented.All operations were completed with robotic assisted approach without conversion. Bilateral and unilateral reimplantation were respectively performed in two and fourteen patients. The mean operative time was 115.0 ± 19.5 min and the mean blood loss was 10.0 ± 1.8 ml. There were no high-grade complications (III-IV on Clavien-Dindo classification) except for one patient. The distal ureteric diameter was reduced from pre operative 1.7 ± 0.5 to 0.6 ± 0.5 cm 6 months post operatively (p 0.05). One child (6.3%) required the second reimplantation for stenosis. The overall operative success rate was 94.4% (17 of 18 ureters) with a mean follow-up of 15.9 ± 7.4 months with no flux detected.Our preliminary experience suggests that our modified robot-assisted laparoscopic extravesical ureteral reimplantation is feasible in infants with good results.

Background: The incidence of melanoma has been increasing over the last 30 years. The most common treatments, such as surgery, chemotherapy, and radiotherapy, frequently cause serious damage to the body. It is therefore critical to develop a new therapeutic strategy for the treatment of melanoma. Objectives: This research aims to evaluate the anti-tumor effect of Neochamaejasmine A (NCA) on B16F10 melanoma cells and the underlying molecular mechanisms. Methods: The CCK-8 kit was utilized to assay the influence of NCA on the vitality of B16F10 cells. Modifications in B16F10 cells morphology were observed using a phase-contrast microscope. Apoptosis of B16F10 melanoma cells was assessed by Hoechst 33258, Annexin V and propidium iodide staining. Cell cycle was detected using a commercial kit by flow cytometry. The mRNA and protein expression levels associated with apoptosis and cell cycle arrest were detected by RT-PCR and Western blot. The expression level of pathway proteins was assessed using Western blot. Result: It was found that the proliferation of B16F10 cells was inhibited by NCA in concentration- and time-dependent manners. NCA promoted apoptosis by halting the cell cycle at the G2/M phase. After treatment with NCA, cell apoptosis was confirmed by Hoechst 33258 staining. NCA triggered the cell cycle to seize at the G2/M stage by downregulating cyclin B1 and cyclin-dependent kinase 2 (CDC2) expression. Moreover, the mRNA and protein expression of cleaved caspase- 9 and Bcl-2-associated X-protein (Bax) were increased, whereas there was a decline in the expression of B-cell lymphoma 2 (Bcl-2). The p-p38/p38 and phosphorylated c-Jun N-terminal kinase (p-JNK/JNK) ratio were also elevated by NCA. The apoptosis and G2/M cell cycle arrest were inhibited in cells co-treated with the p38 inhibitor SB203580 and JNK inhibitor SP600125. The expression of apoptosis-related proteins Bax was decreased, and Bcl-2 was increased. Conclusion: The findings of this study showed that NCA could induce apoptosis and cell cycle arrest in B16F10 melanoma cells by activating JNK and p38 MAPK signaling pathway.

This short Perspective article presents an overview of the discovery of topological $\pi$ modes as well as their physical significance in quantum computing and the understanding of an exotic phase of matter, i.e., the Floquet time crystal. The recent proposals of $2\pi/k$ modes as the generalizations of $\pi$ modes are further elucidated., Comment: 5 pages, 1 figure. Published in Science Bulletin

Background and Aims: Concentric LV remodeling and hypertrophy are common structural abnormalities in patients with heart failure with preserved ejection fraction (HFpEF) and tend to be accompanied by impaired LV function. Assessment of global myocardial work (GMW) using strain-pressure loop may provide more comprehensive assessment of LV myocardial function, overcoming the limitations of the conventional parameters. We investigated the value of GMW in patients with HFpEF and assessed the relationship of GMW with concentric remodeling and hypertrophy.Methods: Consecutive patients with HFpEF (n=107) and sex-matched healthy controls (n=32) were prospectively enrolled. Clinical and conventional echocardiography variables were obtained. Further analyses of offline data were performed to obtain GMW indices including global work index (GWI), global constructive work (GCW), global waste work (GWW), and global work efficiency (GWE). Association of concentric remodeling and hypertrophy with GMW was analyzed by univariate and multivariate analysis.Results: HFpEF patients showed lower GWE (94% vs 96%, PP=0.003) than control group, while GWI (2111 mmHg% vs 2146 mmHg%, P=0.877) and GCW (2369 mmHg% vs 2469 mmHg%, P=0.733) were comparable in the two groups. HFpEF patients with relative wall thickness (RWT) >0.42 had reduced GWE (93% vs 94%, P=0.015) compared to HFpEF patients with RWT≤0.42, while GWI, GCW, and GWW were comparable between these two subgroups. Multivariate analysis showed an independent association of RWT with GWI, GCW, and GWE, respectively.Conclusion: Impaired global myocardial work was detected in patients with HFpEF. Impaired LV GMW may be associated with increased RWT.

Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible pulmonary interstitial disease that seriously affects the patient's quality of life and lifespan. The pathogenesis of IPF has not been clarified, and its treatment is limited to pirfenidone and nintedanib, which only delays the decline of lung function. Alveolar epithelial type 2 (AT2) cells are indispensable in the regeneration and lung surfactant secretion of alveolar epithelial cells. Studies have shown that AT2 cell dysfunction initiates the occurrence and progression of IPF. This review expounds on the AT2 cell dysfunction in IPF, involving senescence, apoptosis, endoplasmic reticulum stress, mitochondrial damage, metabolic reprogramming, and the transitional state of AT2 cells. This article also briefly summarizes potential treatments targeting AT2 cell dysfunction.

Acute myeloid leukemia (AML) is the most common acute leukemia affecting adults. The tight junction protein CLDN4 is closely related to the development of various epithelial cell carcinomas. However, whether CLDN4 contributes to AML development remains unclear. For the first time, we found that expression of CLDN4 is aberrantly up-regulated in AML cells. Knockdown of CLDN4 expression resulted in a dramatic decreased cell growth, elevated apoptosis of AML cells. Further, we revealed that knockdown of CLDN4 inhibits mRNA expression of PIK3R3 and MAP2K2, thus suppresses activation of AKT and ERK1/2. More importantly, activating AKT branch by SC79 partially compromised CLDN4 knockdown induced cell viability inhibition. In addition, we found that higher expression of CLDN4 is connected to worse survival and is an independent indicator of shorter disease free survival (DFS) in AML patients. Together, our results indicate that CLDN4 contributes to AML pathogenesis, and suggests that targeting CLDN4 is a promising option for AML treatment.

A damage identification methodology considering shear deformation was presented in this paper to identify damage to semi-rigid frames with slender beams. On the basis of the successful identification of structural joint damage, the combined joint and member damage of the structure was identified. The objective function was formulated to minimize the discrepancies between the analytical and measured nodal displacements. Damage identification was performed on semi-rigid frame structures with different cross-sectional shapes, and the results were compared with those of ignoring shear deformation. Several frame structures were employed to verify the advantages and efficiency of the proposed method. The results demonstrate that the present method could significantly improve the accuracy of damage identification for semi-rigid frames compared with the method ignoring shear deformation.

BACKGROUND: Unlike fee-for-service Medicare, the Veterans Health Administration (VHA) allows for the provision of concurrent care, incorporating cancer treatment while in hospice. METHODS: We compared trends of aggressive care at end of life between Medicare and VHA decedents with advanced nonsmall cell lung cancer from 2006 to 2012, and the relation between regional level end-of-life care between Medicare and VHA beneficiaries. RESULTS: Among 18,371 Veterans and 25,283 Medicare beneficiaries, aggressive care at end of life decreased 15% in VHA and 4% in SEER (Surveillance, Epidemiology, and End Results)-Medicare (p

We report the discovery of PSR J1909+0122 by the Five-hundred-meter Aperture Spherical radio Telescope (FAST) as part of the Commensal Radio Astronomy FAST Survey (CRAFTS). PSR J1909+0122 has a spin period of 1.257 seconds, a dispersion measure (DM) of 186.2 pc cm-3. The averaged pulse profile shows two distinct components. We performed single-pulse study based on one-hour observation at 1.25 GHz on August 23rd, 2021. We used a threshold of 5 σep to measure the nulling fraction (NF) as 63% ± 1.5%. The longitude resolved fluctuation spectra (LRFS) and FFT spectra of the binary sequences revealed the 30-rotation-period quasi-periodicity of nulling. We examined the reliability of the periodicity by comparing it to random noise injection. The NF, E-dot, and modulation periodicity PM of PSR J1909+0122 were compared with other periodic nulling pulsars, showing the source of J1909+0122 has the second largest NF in the population. Long-term timing observations over six months were used to derive the phase-connected ephemeris of this pulsar. The measured P and P-dot values disfavor dipolar geometry for polar gap models, and the prediction for a space-charge limited flow model in the case of inverse Compton scattering is only just above the death line. In this work, PSR J1909+0122 has revealed possible correlations between nulling behavior and pulsar properties, which will help to shed light on the pulsar emission mechanism and its temporal evolution in future observations.

Purpose: To evaluate the drug-induced liver injury (DILI) adverse events related to antidepressants. Method: Post-marketing cases were obtained from the United States Food and Drug Administration Adverse Events Reporting System (FAERS). Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC). Result: There were a total of 10,355 reported cases of DILI out of a total of 324,588 cases reported from January 2004 to December 2021. Among the 42 antidepressants assessed, nefazodone (n = 47, ROR = 7.79, IC=2.91), fluvoxamine (n = 29, ROR = 4.69, IC=2.20), and clomipramine (n = 24, ROR = 3.97, IC=1.96), were the top three compounds ranked with the highest reporting odds of cholestatic injury. Mianserin (n = 3, ROR = 21.46, IC=3.99), nefazodone (n = 264, ROR = 18.67, IC=3.84), and maprotiline (n = 15, ROR = 5.65, IC=2.39), were the top three compounds ranked with the highest reporting odds of hepatocellular injury. Nefazodone (n = 187, ROR = 12.71, IC=0.48), clomipramine (n = 35, ROR = 2.07, IC=0.26), and mirtazapine (n = 483, ROR = 1.96, IC=0.94) were the top three on drug related severe hepatic disorders. Only nefazodone detected the signals (n = 48, ROR = 18.64, IC=4.16) in the study of hepatic faliure. Conclusion: The data mining of FAERS suggested significant association between DILI and nefazodone. Duloxetine and clomipramine detected the signals on three categories of DILI besaides hepatic failure. Moreover, DILI risk on the new generation of antidepressants should also be taken into consideration.

The short-term prediction of soil moisture variation is a decisive indicator of irrigation scheduling and crop management in agriculture. Traditional soil water dynamic models require complex descriptions of water movement and multiple parameters to calibrate for specific fields, which limit the model’s capability of generalization. Machine learning methods based on large sample datasets can automatically learn the most accurate way of predicting soil moisture with numerous related input variables. However, it could be time consuming in training and model optimization to improve performance. Combining the advantages of both methods, we designed a new soil moisture prediction neural network guided by the water transport driving mechanism. The water balance principle is used to limit the training process with remote sensing-based field-scale evapotranspiration, meteorological rainfall and primary soil water changes calculated from a simplified soil water model. By adding the physics layer to neural network, the demand for large datasets and the requirements of training and optimization are reduced. The prediction of soil moisture is at a half-monthly scale, and we tested the model during the winter wheat growing period. The results show that it requires less training capability to achieve high accuracy. Physics-guided neural networks could act as a better framework for parameter prediction in further researches.

Background First-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib, have been shown to target tumors with L858R (exon 21) and exon 19 deletions, resulting in significant clinical benefits. However, acquired resistance often occurs due to EGFR mutations. Therefore, novel therapeutic strategies for treatment of patients with EGFR-positive tumors are needed. Berberine (BBR) is an active alkaloid extracted from pharmaceutical plants such as Coptis chinensis. Berberine has been shown to significantly inhibit EGFR activity and mediate anticancer effects in multiple preclinical studies. We investigated whether combining BBR with erlotinib could augment erlotinib-induced cell growth inhibition of EGFR-positive cells in a mouse xenograft model. Methods We examined the antitumor activities and potential mechanisms of erlotinib in combination with berberine in vitro and in vivo using the MTT assay, immunoblotting, flow cytometry, and tumor xenograft models. Results In vitro studies with A431 cells showed that synergistic cell growth inhibition by the combination of BBR and erlotinib was associated with significantly greater inhibition of pEGFR and pAKT, and inhibition of cyclin D and Bcl-2 expression compared to that observed in response to BBR or erlotinib alone. The efficacy of the combination treatment was also investigated in nude mice. Consistent with the in vitro results, BBR plus erlotinib significantly reduced tumor growth. Conclusion Our data supported use of BBR in combination with erlotinib as a novel strategy for treatment of patients with EGFR positive tumors.

Heterotopic ossification (HO) severely affects people's lives; however, its pathological mechanism remains poorly understood. Although extracellular DNA (ecDNA) has been shown to play important roles in pathological calcification, its effects in HO development and progression remain unknown. The in vivo rat Achilles tendon injury model and in vitro collagen I calcification model were used to evaluate the effects of ecDNA in the ectopic calcifications and the main cell types involved in those pathological process. Histology, immunofluorescent staining, reverse transcriptase-polymerase chain reaction analysis and micro-computed tomography were used to identify the distribution of macrophage-derived ecDNA and elucidate their roles in HO. The results showed that the amount of ecDNA and ectopic calcification increased significantly and exhibited a strong correlation in the injured tendons of HO model compared with those of the controls, which was accompanied by a significantly increased number of M2 macrophages in the injured tendon. During in vitro co-culture experiments, M2 macrophages calcified the reconstituted type I collagen and ectopic bone collected from the injured tendons of HO rats, while those effects were inhibited by deoxyribonuclease. More importantly, deoxyribonuclease reversed the pathological calcification in the injured rat tendon HO model. The present study showed that ecDNA from M2 macrophages initiates pathological calcification in HO, and the elimination of ecDNA might be developed into a clinical strategy to prevent ectopic mineralization diseases. The use of deoxyribonuclease for the targeted degradation of ecDNA at affected tissue sites provides a potential solution to treat diseases associated with ectopic mineralization.

We investigate the single-pulse emission variations of two pulsars, PSRs J0211+4235 and J0553+4111, observed with the Five-hundred-meter Aperture Spherical Radio Telescope at the 1.25 GHz central frequency. The observation sessions span from December 2020 to July 2021, with 21 and 22 observations for them. The integrated pulse profile of PSR J0211+4235 shows that there is a weak pulse component following the main component. And for PSR J0553+4111, it shows a bimodal profile with a bridge component in the middle. PSR J0211+4235 presents significant nulling phenomenon with nulling dura- tion lasting from 2 to 115 pulses and burst duration lasting from 2 to 113 pulses. The nulling fraction of each observation is determined to be 45% to 55%. No emission greater than three sigma is found in the mean integrated profile of all nulling pulses. In most cases, the pulse energy changes abruptly during the transition from null to burst, while in the transition from burst to null there are two trends: abrupt and gradual. We find that the nulling phenomenon of PSR J0211+4235 is periodic by Fourier transform of the null and burst state. In addition, the single-pulse modulation characteristics of these two pulsars are investigated, and the dis- tribution of modulation index, LRFS, 2DFS are analyzed with PSRSALSA. The left peak of PSR J0553+4111 has intensity modulation. Finally, the polarization property of these two pulsars are obtained through polarization calibration, and their characteristics are analyzed. The possible physical mechanisms of these phenomena are discussed.

Background The evaluation of kidney injury severity is a crucial aspect of medical practice. At present, glomerular filtration rate (GFR) serves as the primary indicator for this assessment. Estimated GFR (eGFR) remains the most frequently utilized parameter in clinical settings. Numerous equations have been formulated based on serum creatinine (Scr) or serum cystatin C (Cysc) levels. However, there is a lack of consensus regarding the efficacy of these equations in assessing eGFR, particularly for elderly individuals in China. This study aimed to evaluate the applicability of the MDRD, MDRDc, CKD-EPI series, BIS1, and FAS equations within the Chinese elderly population. Methods A cohort of 298 elderly patients with measured GFR (mGFR) determined by the dual plasma sample clearance method using 99m-Technetium-diethylenetriamine-pentaacetic acid (99m Tc-DTPA) renal dynamic imaging was enrolled. The patients were categorized into three subgroups based on their mGFR levels. The eGFR performance was examined, taking into account bias, interquartile range (IQR), accuracy P30, and root-mean-square error (RMSE). Bland-Altman plots were employed to verify the validity of eGFR. Results The 298 participants had a median age of 71 years, with 167 (56.0%) being male. In reference to mGFR (48.77 ml/min/1.73 m2), the CKD-EPI-Scr, CKD-EPI-Cysc, CKD-EPI-Scr-Cysc, MDRD, MDRDc, FAS, and BIS1 equations estimated GFR at 50.38, 49.08, 45.28, 51.65, 54.00, 38.73, and 48.80 ml/min/1.73 m2, respectively. Overall, no significant differences in bias were observed among the seven equations (P > 0.05). In terms of IQR, P30, and RMSE, the BIS1 equation demonstrated superior accuracy compared to the other equations (14.61, 72.1%, and 13.53, respectively). When mGFR 2, all equations underestimated the true GFR, with the highest accuracy reaching only 59%. Bland-Altman plots indicated that the BIS1 equation exhibited the highest accuracy, featuring a 95% confidence interval (CI) width of 52.37 when compared to the other equations. Conclusions This study suggested that the BIS1 equation stands out as the most applicable for estimating GFR in Chinese elderly patients with normal renal function or only moderate decline.

Hydraulic fracturing is widely used to stimulate unconventional reservoirs, but a systematic and comprehensive investigation into the hydraulic fracturing process is rare. In this work, a discrete element-lattice Boltzmann method is implemented to simulate the hydro-mechanical behavior in a hydraulic fracturing process. Different influential factors, including injection rates, fluid viscosity, in-situ stress states, heterogeneity of rock strengths, and formation permeability, are considered and their impacts on the initiation and propagation of hydraulic fractures are evaluated. All factors have a significant impact on fracture initiation pressure. A higher injection rate, higher viscosity, and larger in-situ stress increase the initiation pressure, while a higher formation permeability and higher heterogeneity decrease the initiation pressure. Injection rates and heterogeneity degrees have significant impacts on the complexity of generated fractures. Fluid viscosity, in-situ stress states, and formation permeability do not change the geometrical complexity significantly. Hydraulic fractures are usually tensile fractures, but many tensile fractures also have shear displacement. Shear fractures are possible and the shear displacement can be significant under certain conditions, such as a high injection rate, and a high heterogeneity degree.

Radio frequency interference (RFI) is a significant challenge faced by today's radio astronomers. While most past efforts were devoted to cleaning the RFI from the data, we develop a novel method for categorizing and cataloguing RFI for forensic purpose. We present a classifier that categorizes RFI into different types based on features extracted using Principal Component Analysis (PCA) and Fourier analysis. The classifier can identify narrowband non-periodic RFI above 2 sigma, narrowband periodic RFI above 3 sigma, and wideband impulsive RFI above 5 sigma with F1 scores between 0.87 and 0.91 in simulation. This classifier could be used to identify the sources of RFI as well as to clean RFI contamination (particularly in pulsar search). In the long-term analysis of the categorized RFI, we found a special type of drifting periodic RFI that is detrimental to pulsar search. We also found evidences of an increased rate of impulsive RFI when the telescope is pointing toward the cities. These results demonstrate this classifier's potential as a forensic tool for RFI environment monitoring of radio telescopes., Comment: 15 pages, 19 figures

Background: Multiple rib fractures can lead to flail chest with up to 35% mortality rate due to severe pulmonary complications. Current treatments of flail chest remain controversial. Studies have shown that surgical treatments can improve outcomes and reduce mortality, comparing to non-operative treatments. Current surgical fixation methods focus on stabilization of ribs on the outward facing side, and they require division of intercostal muscles. Damages to surrounding nerves and vessels may lead to chronic pain. This study tests a novel interior fixation method that minimizes neurovascular injuries. Methods: Twelve healthy canines were divided in two surgical operation groups for exterior and interior fixation using titanium metal plates. Osteotomy with oblique fractures was prepared under general anesthesia. Exterior fixation was performed in open surgery. Interior fixation was minimally invasive using custom made tools including a flexible shaft extension screwdriver, solid plate stand, guiding wire loop and metal plates with threaded holes. Results: Respiratory and cardiovascular functions (RR, PO2, PCO2, SpO2, and HR) together with body temperature were measured before anesthesia and within 48 hours after surgery. The difference in measurements was not statistically significant between the two groups before surgery with P values greater than 0.05. However, the interior group canines had better RR and PO2 values starting from the 24th hour, and better PCO2, SpO2, and HR values starting from the 48th hour. It took longer operation time to complete the minimally invasive interior fixation surgery (P value less than 0.001), but the total blood loss was less than the exterior fixation group (P value less than 0.001). Results also showed that interior group canines suffered less pain, and they had quicker recovery in gastrointestinal and physical mobility. Conclusions: The investigative interior fixation method was safe and effective in rib stabilization on a canine rib fracture model, comparing to the exterior fixation method. The interior fixation was minimally invasive, with less damages to tissues and nerves surrounding the ribs, leading to better postoperative outcomes.