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This study examined the potential correlation between the immoderate intake of sugar-sweetened beverages (SSBs) and the subsequent rate of diabetes remission (DR). 206 individuals who met the eligibility criteria between January 2019 and June 2022 were recruited. Inquiries were conducted to gather information on the participants’ beverage consumption before the onset. Subsequently, the participants were separated into the diabetes remission group (DR group) and nondiabetes remission group (NDR group) depending on whether they met the diagnostic criteria for diabetes remission. Baseline clinical elements within the two groups were juxtaposed, and factors influencing diabetes remission were identified through logistic regression analyses. The cutoff values of each critical factor were determined based on the receiver operating characteristic curve. One hundred and nine patients reported a history of SSB consumption, while the remaining 58 reported no such history. After 1 year, 40 patients achieved remission from diabetes. Compared with the NDR group, a higher SSBs ratio, body mass index (BMI), and blood creatinine (BCr) was observed in the DR group after adjusting for confounders, SSBs (odds ratio [OR] = 3.503; 95% confidence interval [CI] = 1.334–9.202; p = 0.011) and BCr (OR = 1.038; 95% CI = 1.003–1.079; p = 0.042) emerged as independent predictors of DR. The composite index of SSBs and BCr efficaciously predicted DR (area under the ROC curve [AUC] = 0.810, p < 0.001). SSBs and BCr were independent risk factors for DR. The amalgamation of these markers could more accurately predict DR.

Abstract In chronic kidney disease (CKD), renal fibrosis is an unavoidable result of various manifestations. However, its pathogenesis is not yet fully understood. Here, we revealed the novel role of Homeobox D10 (HOXD10) in CKD-related fibrosis. HOXD10 expression was downregulated in CKD-related in vitro and in vivo fibrosis models. UUO model mice were administered adeno-associated virus (AAV) containing HOXD10, and HOXD10 overexpression plasmids were introduced into human proximal tubular epithelial cells induced by TGF-β1. The levels of iron, reactive oxygen species (ROS), lipid ROS, the oxidized glutathione/total glutathione (GSSG/GSH) ratio, malonaldehyde (MDA), and superoxide dismutase (SOD) were determined using respective assay kits. Treatment with AAV–HOXD10 significantly attenuated fibrosis and renal dysfunction in UUO model mice by inhibiting NOX4 transcription, ferroptosis pathway activation, and oxidative stress. High levels of NOX4 transcription, ferroptosis pathway activation and profibrotic gene expression induced by TGF-β1/erastin (a ferroptosis agonist) were abrogated by HOXD10 overexpression in HK-2 cells. Moreover, bisulfite sequencing PCR result determined that HOXD10 showed a hypermethylated level in TGF-β1-treated HK-2 cells. The binding of HOXD10 to the NOX4 promoter was confirmed by chromatin immunoprecipitation (ChIP) analysis and dual-luciferase reporter assays. Targeting HOXD10 may represent an innovative therapeutic strategy for fibrosis treatment in CKD.

BackgroundThe decline in physiological functions in the older people is frequently accompanied with pain and frailty, yet the causal connection between frailty and pain remains uncertain. In this study, we utilized a two-sample Mendelian randomization (MR) approach to investigate the potential causal association between frailty and pain.MethodsTwo-sample bidirectional MR was conducted using summary data from genome-wide association studies to examine the potential causal relationship between frailty (defined by the frailty index and frailty phenotype) and pain. Summary genome wide association statistics were extracted from populations of European ancestry. We also investigated the causal relationship between frailty and site-specific pain, including joint pain, limb pain, thoracic spine pain and low back pain. Causal effects were estimated using the inverse variance weighting method. Sensitivity analyses were performed to validate the robustness of the results.ResultsGenetic predisposition to frailty was associated with an increased risk of pain (frailty phenotype odds ratio [OR]: 1.73; P = 3.54 × 10–6, frailty index OR: 1.36; P = 2.43 × 10–4). Meanwhile, individuals with a genetic inclination toward pain had a higher risk of developing frailty. Regarding site-specific pain, genetic prediction of the frailty phenotype increased the occurrence risk of joint pain, limb pain and low back pain. Reverse MR analysis further showed that limb pain and low back pain were associated with an increased risk of frailty occurrence.ConclusionThis study presented evidence supporting a bidirectional causal relationship between frailty and pain. We highlighted the significance of addressing pain to prevent frailty and recommend the inclusion of pain assessment in the evaluation system for frailty.

Congenital melanocytic nevi (CMN) are common skin tumors. Large and specially located nevi cannot be completely removed by surgery, posing the risks of both cosmetic deformities and potential malignancy. Nonsurgical treatments, such as laser therapy and physical dermabrasion, can overcome the limitations of surgery; however, the high rate of repigmentation remains an unresolved global challenge. We conducted a self-controlled observational study of a patient with a nevus on the chest. Two areas of the lesion were treated with an Er:YAG laser and 5% imiquimod cream was applied to one of these areas. After nearly 7-months of follow-up, we observed a significant difference in color between the two areas, suggesting that topical imiquimod may inhibit repigmentation and significantly enhance the effectiveness of laser treatment.

Abstract Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.

To avoid the secondary frequency dip caused by the steep drop of the electrical power of wind turbines (WTs) at the end of frequency support stage, the torque limit-based iner-tial control (TLIC) method sets the power reference as a linear function of rotor speed, rather than the step form for the step-wise inertial control. However, the compensation effect on the frequency nadir (FN) caused by the load surge is weakened as the TLIC power is no longer in the step form. Specifically, the maximum point of the frequency response component (FRC) contributed by TLIC occurs earlier than the minimum point of FRC corresponding to the load surge, so that the FN cannot be adequately raised. Therefore, this paper first investigates the relation between the peak and nadir times of FRCs stimulated by the TLIC and load power. On this basis, with the compensation principle of matching the peak and nadir times of FRCs, the improved TLIC method based on delayed support is proposed. Finally, the effectiveness of the proposed method is validated via the experiments on the test bench of wind-integrated power system.

Objective: This study explores the 22-year evolution of Infantile Hemangiomas (IHs) treatment strategies at a single-center hospital, aiming to establish an individualized IHs management protocol.Methods: Retrospective review of IHs infants 2000–2022 at the Department of Plastic Surgery, Jiangxi Provincial Children’s Hospital.Results: In our study of 27,513 IHs cases, 72.2% were female, with the median age at first hospital visit being 25 days. The majority of cases had localized and superficial lesions primarily on the head, face, and neck (67.5%). Ulceration rates fell from 21.1% to 12.6% with the introduction of propranolol. Management strategies have shifted over time, with the proportion of cases undergoing expectant management dropping from 32.9% to 12.4%. Since 2008, 26.1% of patients were treated with oral propranolol, largely replacing corticosteroids. Topical β-blockers have been used in 12.1% of cases, leading to a reduction in local injection therapy from 20.8% to 13.2%. Laser therapy, introduced in 2016, has been used in 13.8% of cases, while surgical excision has dropped from 25.0% to 8.5% due to alternative treatment options. Combination therapy was used in 8.8% of cases post-2015, indicating a rising trend. Drawing from the evolution of IHs management strategies, an individualized protocol for the management of IHs was successfully established.Conclusion: Treatment for IHs has evolved over recent decades, with less invasive medical interventions increasingly replacing more invasive methods. Furthermore, a personalized treatment protocol established in this study could boost the cure rate of IHs while minimizing potential side effects and complications.

Many studies have explored the role of consonant, vowel, and tone in Chinese word identification or sentence comprehension. However, few studies have explored their roles and neural basis during Chinese word production, especially when involving neural basis. The present fNIRS study investigated the neural mechanisms of consonant, vowel, and tone processing during Chinese typing. Participants were asked to name the Chinese characters displayed on a computer screen by typing on a keyboard while hearing a simultaneously presented auditory stimulus. The auditory stimulus was either consistent with the characters’ pronunciation (consistent condition) or mismatched in the consonant, vowel, or tone of the character pronunciation. The fNIRS results showed that compared with the consistent condition (as baseline), the consonant mismatch condition evoked lower levels of oxygenated hemoglobin (HbO) activation in the left inferior frontal gyrus Broca’s triangle and left superior temporal gyrus. Vowel mismatch condition evoked a higher level of HbO activation in the top of the left inferior frontal gyrus and left middle frontal gyrus. The regions and patterns of brain activation evoked by tone mismatch were the same as those of vowel mismatch. The study indicated that consonant, vowel and tone all play a role in Chinese character production. The sensitive brain areas were all in the left hemisphere. However, the neural mechanism of consonant processing differed from vowel processing in both brain regions and patterns, while tone and vowel processing shared the same regions.

Objective Peritoneal dialysis (PD) requires high patient conscientiousness. Therefore, we aimed to investigate the relationship between conscientiousness score and prognosis in PD patients.Methods The ten-item Big Five Personality Inventory’s Chinese version was used to assess the conscientiousness score. Basic clinical information, prior medical history, hematological examination results, the occurrence of the first peritonitis and catheter-related infection, the start of hemodialysis, and the time of renal transplantation were collected. The patients were split into two groups, high and low conscientiousness groups, based on the mean value of the conscientiousness score. The differences in prognostic indicators were compared between groups, and the association between conscientiousness score and prognostic indicators in PD patients was assessed.Results Enrolled PD patients were divided into low conscientiousness group 103 and high conscientiousness group 98. There were significant differences in serum albumin (p = 0.021) and iPTH (p = 0.045) between the two groups. Multivariate Cox regression analysis identified conscientiousness score as an independent risk factor for the development of first peritonitis (HR = 0.558, 95% CI 0.400–0.779, p = 0.001) and first catheter-related infection (HR = 0.544, 95% CI 0.308–0.962, p = 0.036) in PD patients. Conscientiousness score (HR = 2.377, 95% CI 1.109–5.095, p = 0.026) was independently associated with renal transplantation.Conclusion Conscientiousness personality is closely related to the prognosis of PD patients.

Abstract Although the efficacy of propranolol in the treatment of infantile hemangioma (IH) has been well established, clinical data on the safety and tolerability of propranolol in neonates are still lacking. In this work, clinical data of 112 neonates with IH were analyzed retrospectively. All of the patients were evaluated in the hospital at the beginning of the treatment and later in outpatient settings during the treatment. Each time, the following monitoring methods were applied: physical examination, ultrasound echocardiography (UCG), electrocardiography (ECG), blood pressure (BP), heart rate (HR), and basic laboratory tests including blood glucose (BG), liver function, blood potassium, thyroid function. There was a significant reduction in BP and HR at the initiation of treatment. The incidences of bradycardia and hypoglycemia were observed to be increased with the prolong duration of treatment, but not prolonged PR interval. During the course of the therapy, the risk of hyperkalemia and hypothyroidism was reached maximum at the 2 months and 3 months, respectively. Physical growth index including average height, weight and head circumference was not influenced by the treatment. The observed adverse effects were majority mild and only 3 patients needed to rest for 7 days due to severe diarrhea before restarting treatment. This study demonstrated that propranolol is safe and well-tolerated by properly selected young infants with IH. No serious adverse events were observed.

Abstract Cystoscopy is the current gold standard for diagnosing bladder cancer (Bca), but its invasive nature often results in patient discomfort. This study aims to debise a new strategy to enhance BCa detection. We collected data from 30 BCa patients between January and June 2022. We obtained spontaneously voided urine specimens from these patients before and after administering extracorporeal bladder vibration. These specimens underwent routine cytologic examination and fluorescence in situ hybridization (FISH). Furthermore, we conducted a follow‐up 3 months postoperation. We recollected urine specimens before and after extracorporeal bladder vibration, repeating the cytologic examination and FISH. Our findings indicated an increase in the number of exfoliated cells in patients' urine postvibration compared to previbration. The liquid‐based cell staining results showed an increased detection rate of abnormal cells in the urinary sediment of patients with both low and high‐grade urothelial carcinoma postvibration. Similarly, the FISH results revealed an increased detection rate of CEP3 and CEP7 positive cells postvibration. Additionally, 3 months postoperation, we found abnormal cells in the urine of one patient previbration and in three patients postvibration. Further cystoscopic biopsy confirmed that these three patients had developed tumor recurrence. Our study substantiates that the extracorporeal bladder vibration assay significantly enhances BCa detection and the prediction of tumor recurrence. This method is simple, quick, and cost‐effective, making it a promising approach worthy of widespread clinical application.

Optimal torque (OT) control is a widely used method for maximum power point tracking (MPPT) due to its simplicity. In order to overcome the adverse impacts of turbulent wind speed variations on MPPT, in several methods, modification factors have been proposed to dynamically modify the ideal power curve for OT control. However, this paper finds that the update cycles used in existing methods to adjust power curve modification factors are very long and hence these factors are difficult to be updated in a timely manner along with the wind speed variations. This thereby may deteriorate the effectiveness of wind energy extraction. Therefore, an optimal decreased torque gain (DTG) control method is proposed in this paper. Based on the persistence method, an offline mapping from the wind speed and rotor speed to optimal modification factors is established via optimal control theory. The power curve can be periodically modified online through the mapping relationship. In this method, the update cycles for these power curve modification factors are shortened from tens of minutes to seconds. The simulations and experiments show that the proposed method is more efficient than others in terms of energy extraction under varying wind speeds, especially for turbulent wind cases.

Abstract Purpose In this manuscript, we purposed to identify the prognostic factors for treatment of lymphatic malformations in children using polidocanol foam combined with pingyangmycin and to construct nomogram for predicting sclerotherapy response. Methods A retrospective analysis of 77 children having LMs who underwent sclerotherapy using polidocanol foam combined with pingyangmycin under ultrasound display from January 2017 to April 2020 was done. The clinical response was graded as excellent (≥ 90%), good (≥ 50%,

Candida auris is a multidrug-resistant human fungal pathogen responsible for nosocomial outbreaks worldwide. Here, the authors identify differential innate immune responses induced by C. auris and Candida albicans in vitro and in vivo, which correlate with structural features of the cell wall.

The transition metal iron plays a crucial role in living cells. However, high levels of iron are potentially toxic through the production of reactive oxygen species (ROS), serving as a deterrent to the commensal fungus Candida albicans for colonization in the iron-rich gastrointestinal tract. We observe that the mutant lacking an iron-responsive transcription factor Hap43 is hyper-fit for colonization in murine gut. We demonstrate that high iron specifically triggers multiple post-translational modifications and proteasomal degradation of Hap43, a vital process guaranteeing the precision of intestinal ROS detoxification. Reduced levels of Hap43 de-repress the expression of antioxidant genes and therefore alleviate the deleterious ROS derived from iron metabolism. Our data reveal that Hap43 functions as a negative regulator for oxidative stress adaptation of C. albicans to gut colonization and thereby provide a new insight into understanding the interplay between iron homeostasis and fungal commensalism.

The deformation behavior of a dam can comprehensively reflect its structural state. By comparing the actual response with model predictions, dam deformation prediction models can detect anomalies for effective advance warning. Most existing dam deformation prediction models are implemented within a single-step prediction framework; the single-time-step output of these models cannot represent the variation trend in the dam deformation, which may contain important information on dam evolution during the prediction period. Compared with the single value prediction, predicting the tendency of dam deformation in the short term can better interpret the dam’s structural health status. Aiming to capture the short-term variation trends of dam deformation, a multi-step displacement prediction model of concrete dams is proposed by combining the complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) algorithm, the k-harmonic means (KHM) algorithm, and the error minimized extreme learning machine (EM-ELM) algorithm. The model can be divided into three stages: (1) The CEEMDAN algorithm is adopted to decompose dam displacement series into different signals according to their timing characteristics. Moreover, the sample entropy (SE) method is used to remove the noise contained in the decomposed signals. (2) The KHM clustering algorithm is employed to cluster the denoised data with similar characteristics. Furthermore, the sparrow search algorithm (SSA) is utilized to optimize the KHM algorithm to avoid the local optimal problem. (3) A multi-step prediction model to capture the short-term variation of dam displacement is established based on the clustered data. Engineering examples show that the model has good prediction performance and strong robustness, demonstrating the feasibility of applying the proposed model to the multi-step forecasting of dam displacement.

Background: We previously reported that interstitial injection of bleomycin (BLM) reduces the size of early-stage extracranial arteriovenous malformation (AVM). Here, we sought to investigate the potential mechanism of BLM in treating extracranial AVM. Methods: Samples of human extracranial AVM (n=3) with no pharmacological treatment were harvested. AVM endothelial cells were isolated and cultured in primary cell culture. The transcriptome was examined using RNA-sequencing, and differentially expressed C-type lectin domain family 14 member A (CLEC14A) was validated at the transcriptomic and protein levels. Immunocytochemical staining of CLEC14A was performed in samples of human extracranial AVM, with and without BLM treatment. Results: Through second-generation sequencing, we found that the expression of 5 689 genes were differentially increased or decreased following 24-h BLM stimulation. We found that CLEC14A may play an important role in the progression of AVM and can be inhibited by BLM treatment. Conclusion: BLM inhibited CLEC14A expression to attenuate the progression of AVM.

Quantitative photoacoustic tomography (QPAT) is a valuable tool in characterizing ovarian lesions for accurate diagnosis. However, accurately reconstructing a lesion’s optical absorption distributions from photoacoustic signals measured with multiple wavelengths is challenging because it involves an ill-posed inverse problem with three unknowns: the Grüneisen parameter (Γ), the absorption distribution, and the optical fluence (ϕ). Here, we propose a novel ultrasound-enhanced Unet model (US-Unet) that reconstructs optical absorption distribution from PAT data. A pre-trained ResNet-18 extracts the US features typically identified as morphologies of suspicious ovarian lesions, and a Unet is implemented to reconstruct optical absorption coefficient maps, using the initial pressure and US features extracted by ResNet-18. To test this US-Unet model, we calculated the blood oxygenation saturation values and total hemoglobin concentrations from 655 regions of interest (ROIs) (421 benign, 200 malignant, and 34 borderline ROIs) obtained from clinical images of 35 patients with ovarian/adnexal lesions. A logistic regression model was used to compute the ROC, the area under the ROC curve (AUC) was 0.94, and the accuracy was 0.89. To the best of our knowledge, this is the first study to reconstruct quantitative PAT with PA signals and US-based structural features.

Abstract Background This study aimed to detect the effect of angiotensin receptor 1 (AT1) knock out (KO) on spermatogenesis and hypothalamic-pituitary–gonadal (HPG) axis hormone expression. Methods Normal C57BL/6 male mice were used as control group or treated with angiotensin receptor blocker, in addition heterozygous ± AT1KO mice were generated. After caged at a ratio of 2 to 1 with females, pregnancy rates of female mice were determined by detection of vaginal plugs. Deformity rate of spermatozoa was evaluated by eosin staining and morphology evaluation. The AT1 mRNA expression in the testes of male ± AT1KO mice was detected by quantitative real-time polymerase chain reaction (QRT-PCR). Serum GnRH level was determined by ELISA. Results Compared to control, ± AT1KO mice showed reduced expression of AT1 in testes, pituitary and hypothalamus. In addition, decreased level of GnRH, but not follicle stimulating hormone (FSH) or luteinizing hormone (LH), in ± AT1KO mice was detected. Treatment with angiotensin receptor blocker (ARB) did not have significant effects on HPG hormones. ± AT1KO mice exhibited male infertility and significant abnormality of sperm morphology. Conclusion Reduced AT1 knockout resulted in male infertility, potentially by inducing abnormal spermatogenesis. Both testis and HPG axis signaling may be involved.

Abstract Background Erythema induratum of Bazin (EIB) is a rare cutaneous manifestation of tuberculosis (TB) that frequently occurs in middle-aged women. The clinical manifestations of EIB can mimic various skin diseases, easily leading to misdiagnosis or underdiagnosis. We report a case of a 16-year-old Chinese girl who initially presented with EIB and was subsequently diagnosed with cavitary TB. Case presentation The patient is a 16-year-old Chinese girl who presented with clusters of erythematous subcutaneous nodules on the posterior part of her right lower leg matching the clinical manifestations of EIB but was otherwise asymptomatic. The patient was subsequently diagnosed with cavitary TB on the basis of a positive result from a T-SPOT.TB test and the observation of cavitary lung lesions in chest computed tomography scanning. A good clinical response was observed in the patient after the initial phase of a standard 6-month antibiotic regimen. Conclusions Adolescents infected with Mycobacterium tuberculosis frequently present atypical symptoms. Cutaneous manifestations of tuberculosis in adolescents can be considered good clinical indicators to predict the underlying disease. Strong clinical suspicion is required for a prompt diagnosis in adolescents with EIB.

Abstract Over the last decade, more than 10 independent SNPs have been discovered to be associated with the risk of renal cell carcinoma among different populations. However, the biological functions of them remain poorly understood. In this study, we performed eQTL analysis, ChIP-PCR, luciferase reporter assay, and Cox regression analysis to identify the functional role and underlying mechanism of rs67311347 in RCC. The ENCORI database, which contains the lncRNA–miRNA–mRNA interactions, was used to explore the possible target miRNA of ENTPD3-AS1. The results showed that the G > A mutation of rs67311347 created a binding motif of ZNF8 and subsequently upregulated ENTPD3-AS1 expression by acting as an enhancer. The TCGA-KIRC and our cohorts both confirmed the downregulation of ENTPD3-AS1 in RCC tissues and demonstrated that increased ENTPD3-AS1 expression was associated with good OS and PFS. Furthermore, ENTPD3-AS1 interacted with miR-155-5p and activated the expression of HIF-1α, which was an important tumor suppressor gene in the development of RCC. The functional experiments revealed that overexpression of ENTPD3-AS1 inhibited cell proliferation in RCC cell lines and the effect could be rescued by knocking down HIF-1α. Our findings reveal that SNP-mediated lncRNA-ENTPD3-AS1 upregulation suppresses renal cell carcinoma via miR-155/HIF-1α signaling.

ABSTRACT: Background: Despite many advances in the treatment for extracranial arteriovenous malformations (AVMs), they still result in tedious dissection and potential unacceptable complications, particularly in children. Therefore, this study aimed to investigate the efficacy and safety of intralesional interstitial injection of bleomycin for the treatment of children with AVMs. Methods: A total of 10 children (6 boys and 4 girls) with AVMs were treated with serial interstitial bleomycin injections between May 2014 and January 2017. Maximum single doses of 15 U and 1 U/kg per session were administered for six sessions at a 1-month interval. Therapeutic effectiveness was evaluated and classified into four categories: complete response (CR), partial response (PR), no response, and worsening at 3 months after the last session. Further clinical follow-up outcomes were classified as improved, stable, or aggravated. Adverse events were recorded according to the Society of Interventional Radiology classification. Results: All 10 children completed the sessions and follow-ups. CR occurred in 3 (30%) patients, PR in 6 (60%), and no response in 1 (20%). Minor complications (class A) included maculopapular rash, bulla, vomiting, and hyperpigmentation, whereas no major complications occurred. Conclusion: Intralesional interstitial injection of bleomycin is a feasible approach for the treatment of AVMs in children and provides safe and effective outcomes. This method may be an earlier treatment alternative in children to prevent potential destructive progression, considering the serious complications of currently available therapeutic methods.

Abstract Background Considering that current peritoneal dialysis has its own shortcomings, In this study, the Seldinger technique was modified to explore the relationship between different catheter placement methods of peritoneal dialysis and short-term postoperative complications. Methods We retrospectively analyzed the data of 157 patients who received peritoneal dialysis in the Department of Nephrology of our hospital from January 2017 to December 2019. According to different catheter placement methods, the patients were divided into three groups: 111 cases of open surgery technique, 23 cases of Seldinger technique, and 23 cases of modified Seldinger technique (ultrasound-guided Veress needle puncture). The general data, laboratory indexes, and abdominal infection and catheter-related complications within one month postoperatively were collected. Results There were 48 (31.0 %) cases of complications in 157 patients within one month postoperatively, which were mainly catheter-related complications (45 cases, 29.0 %). The incidence of catheter tip peritoneal drift (catheter migration) in the three groups was 27.3 %, 39.1 %, and 9.1 %, respectively, with no significant difference between groups (P = 0.069). Univariate logistic regression analysis showed that the systolic blood pressure, history of abdominal and pelvic surgery, creatinine, and modified Seldinger technique were possible impact factors of catheter migration (P

Objective To explore the efficacy and short-term complications of a modified technique to percutaneously insert a peritoneal dialysis catheter. Methods We reviewed the outcomes of 94 patients who underwent peritoneal dialysis catheterization between October 2017 and April 2020. Of these, 47 cases were placed by a conventional Seldinger technique, whereas 47 cases were placed by a modified technique based on the Seldinger method. The success rates of the catheter insertion and three-month postoperative complications were compared between these two groups. Results The catheter insertion success rates were comparable between the two groups: 93.6% in the conventional technique group and 97.9% in the modified technique group (p = 0.307). The incidence of postoperative catheter migration was lower using the modified technique (4.3%) than the conventional technique (18.3%) (p = 0.037). None of the patients in the modified technique group had postoperative dialysate leakage, whereas this occurred in 9.0% of patients in the conventional technique group (p = 0.036). There were no statistically significant differences in the incidence of postoperative bleeding, infection, or visceral damage between the two groups. Conclusions The modified Seldinger technique for percutaneous peritoneal dialysis catheter insertion reduced the short-term postoperative complications of catheter migration and dialysate leakage, with a comparable successful catheter insertion rate compared with the conventional Seldinger technique.

Chronic kidney disease (CKD) is a worldwide public health problem that is caused by repeated injuries to the glomerulus or renal tubules. Renal fibrosis commonly accompanies CKD, and it is histologically characterized by excessive deposition of extracellular matrix proteins, such as fibronectin and collagen I, in interstitial areas. Indirect in vivo experimental data suggest that renal asymmetric dimethylarginine (ADMA) exerts antifibrotic activity in CKD. In this study, we aimed to demonstrate that renal ADMA has a direct effect on fibrosis in vivo. Normal saline, ADMA, nonsense control siRNA, Ddah1 siRNA or Ddah2 siRNA was administered into the kidney through the left ureter in a mouse model of unilateral ureteral obstruction (UUO). UUO kidneys were harvested at day 1 or 7. Western blotting was performed to assess the expression of ADMA, DDAH1 and DDAH2 and the expression of fibrotic markers, such as fibronectin, collagen I, α‐smooth muscle actin, phosphorylation of Smad3 and connective tissue growth factor. Masson’s trichrome staining was used to further evaluate renal fibrosis. We observed that intrarenal administration of ADMA increased the renal accumulation of ADMA and attenuated renal fibrosis at days 1 and 7. Knockdown of Ddah1 or Ddah2 increased the amount of ADMA in UUO kidneys and inhibited the expression of fibrotic proteins at days 1 and 7, which was further confirmed by Masson’s staining. Thus, our in vivo data suggest that renal ADMA exerts direct antifibrotic effects in a mouse model of UUO.

A novel precast composite column with L-shape steels and infilled reinforced concrete (LSRC) is proposed and assessed by experimental research and numerical simulation. The LSRC column is constructed with four L-shape steels placing at corners, a reinforced cage placing outside and the casted concrete. The L-shape steels are connected by batten plates and the reinforcement cage is made up of longitudinal bars, hoops, and two-way ties. In this paper, 3 LSRC slender columns and a conventional concrete-filled steel tube column with encased concrete (CFTEC) are tested and compared to investigate their failure modes, flexural strength, and strains of concrete and steel at mid-span. The results show that the LSRC column has more sufficient plastic deformation ability and steel utilization than the CFTEC column, and exhibits the typical flexural failure mode. Furthermore, the 3D finite element model is also established to analyze the contribution of components, interaction mechanism between steel angle and concrete, and the effect of different factors on flexural behavior of LSRC columns. Based on the test and numerical results, the formula for calculating the bending capacity of LSRC column is proposed, and the predicted results agree well with the experimental and numerical values.

Abstract Congenital melanocytic nevus (CMN) represent a benign proliferative skin disease in the epidermis and dermis. CMN are historically known to be associated with activating NRAS or BRAF mutations. Melanoma frequently harbors the BRAF p.Val600Glu mutation, which is also commonly found in benign nevi. A recent study reported mutation of MAP2K1, a downstream effector of the RAS-RAF-MEK pathway, in melanoma with an overall frequency of 8%. Later, in 2019, Jansen P detected one activating MAP2K1 mutation in acral nevi. However, it is unknown whether MAP2K1 mutations are common in CMN, and how MAP2K1 contributes to the pathogenesis of CMN remains to be determined. In this study, we report one patient clinically and histologically diagnosed with CMN, with the MAP2K1 germline mutation and a BRAF p.Val600Glu somatic hit in the lesion. To the best of our knowledge, this is the first report of the coexistence of mutated BRAF and MAP2K1 in CMN, which may suggest that MAP2K1 mutations contribute to the occurrence and development of nevus expanding our knowledge of the genetics of CMN.

Abstract Congenital melanocytic nevus (CMN) is a benign proliferative skin disease in the epidermis and dermis. Large to giant CMNs are estimated to be associated with an increased lifetime risk of malignancy. It is necessary to estimate and monitor the risk of malignant transformation for giant CMNs. To date, the clinical “ABCD” criteria and immunohistochemistry studies can be confusing and, to some extent, subjective. Accordingly, the elucidation of genomic analyses of nevi is required to better understand the malignant transformation of CMNs. Here, we describe two large to giant CMNs of the scalp with opposite clinical-histological and molecular evaluations of potential malignancy risk. To our knowledge, this is the first description of a genetic study of large to giant CMNs of the scalp in East Asia. We recommend reviewing the molecular diagnosis together with careful medical history and histological information to facilitate the evaluation of the potential malignancy risk.

Introduction Sclerostin has been reported to be a novel biomarker associated with the bone-vascular axis. In this study, we determined the relationships between serum sclerostin and all-cause mortality, the prevalence of cardiovascular events (CVEs), and coronary artery calcifications (CACs) in dialysis patients. Methods A total of 165 dialysis patients (84 hemodialysis [HD] and 81 peritoneal dialysis [PD]) were enrolled in this study. We performed multivariable linear regression analysis to test the relationships between serum sclerostin levels and demographics and clinical parameters. We also performed Cox proportional hazard regression analysis to determine independent predictors of overall survival and CVEs. Results The median serum sclerostin level was 250.9 pg/mL in dialysis patients. Kaplan–Meier analysis showed that both overall and CVE-free survival rates were significantly lower in the high serum sclerostin group (serum sclerostin level >250.9 pg/mL) compared to the low serum sclerostin group (serum sclerostin level ≤250.9 pg/mL) in patients with PD (p 0.05). Conclusions A low serum sclerostin was associated with better overall survival and lower prevalence of CVEs in patients with PD, but had no relationships in patients with HD. We found that serum sclerostin level was not correlated with CACs in either patients with HD or PD.

Chlorinated paraffins (CPs) are produced in large amounts and used worldwide. Dietary intake is the primary pathway for the exposure of pets to CPs, but limited information is available concerning the potential contamination of pet food by CPs. In the present study, the concentrations and congener group profiles of short-chain CPs (SCCPs) and medium-chain CPs (MCCPs) were assessed in 35 imported commercial dry cat and dog foods collected in China, and the estimated daily intakes of SCCPs and MCCPs for cats and dogs through the consumption of such foods was calculated. The concentrations of SCCPs and MCCPs in the cat and dog foods were determined to be in the ranges of 108–45,300 ng/g (median: 1340 ng/g) and 3.8–52,700 ng/g (median: 11 ng/g), respectively. The predominant congener groups were C10Cl6 for SCCPs and C14Cl7-8 for MCCPs. The high levels of CPs found in certain pet foods suggest the potential for adverse health effects.

Summary: Successful host colonization by fungi in fluctuating niches requires response and adaptation to multiple environmental stresses. However, our understanding about how fungal species thrive in the gastrointestinal (GI) ecosystem by combing multifaceted nutritional stress with respect to homeostatic host-commensal interactions is still in its infancy. Here, we discover that depletion of the phosphate transceptor Pho84 across multiple fungal species encountered a substantial cost in gastrointestinal colonization. Mechanistically, Pho84 enhances the gastrointestinal commensalism via a dual-action activity, coordinating both phosphate uptake and TOR activation by induction of the transcriptional regulator Try4 and downstream commensalism-related transcription. As such, Pho84 promotes Candida albicans commensalism, but this does not translate into enhanced pathogenicity. Thus, our study uncovers a specific nutrient-dependent dual-action regulatory pathway for Pho84 on fungal commensalism.

In order to reduce the damage sustained by the substructure of bridges during an earthquake, reduce economic loss, avoid casualties, and ensure the quick repair of bridges after an earthquake, this paper, inspired by the good seismic performance of the rhombic opening in the shear wall structure, proposes a precast segmental concrete-filled steel tubular (PSCFST) pier with external replaceable energy-dissipating links (EREDL).Through finite element simulation analysis, it can be found that the energy dissipation capacity of a PSCFST pier with external EREDL is increased by 104% compared with that of a PSCFST pier without EREDL, and the lateral bearing capacity is increased by 76.9%. Through parameter analysis, it can be found that the change of initial prestress has little effect on the energy dissipation capacity of PSCFST piers, and the seismic performance of PSCFST piers can be improved by properly increasing the ultimate tensile strength of the energy dissipator materials. Compared with the energy dissipators made of Q235 steel, the energy dissipation capacity of PSCFST piers made of Q435 steel energy dissipators is increased by about 85.4%; At the same time, the thicker the energy dissipator, the stronger the energy dissipation capacity of the PSCFST pier, and the lateral bearing capacity is further improved.

Abstract: In this study, waterjet peening (WJP) treatments under different water pressures were utilized to improve the mechanical properties of 304 stainless steel. The surface morphologies, microstructures, phases, and mechanical properties under different pressures in the WJP process were systematically investigated. The results show that WJP treatments successfully introduced a hardening layer and residual compressive stress. The optimal hardening layer, hardness, residual compressive stress, tensile strength, and ductility were all recorded at the pressure of 200 MPa. The improved hardness, tensile strength, and ductility of 304 stainless steel treated with WJP treatments at the pressure of 200 MPa can be attributed to the hardening layer with much apparent grain refinement effect, phase transformation, smaller surface roughness, and a specific residual compressive stress, as compared with the WJP treatments under other water pressures.

In order to further promote the application of segment-assembled bridge piers in medium- and high-intensity areas, and to reduce the post-earthquake damage and repair cost of bridge piers, in this paper, a precast segmental concrete-filled steel-tube bridge pier (PSCFSTBP) with an external arched energy dissipation device (AEDD) is proposed. Firstly, the effectiveness of the finite-element analysis software ABAQUS 6.14-4 is proved by the test results of the PSCFSTBP and the corresponding finite-element model analysis results. Secondly, ABAQUS 6.14-4 was used to establish four-segment PSCFSTBP models with four different structural forms (non-energy dissipation device, external arch steel plate, external vertical steel plate, and external AEDD), and the seismic performance of each model was compared and analyzed under reciprocating displacement loading. The results show that compared with the PSCFSTBP with an external AEDD, the lateral bearing capacity of the PSCFSTBP with an external vertical steel plate is increased by about 11.9%, and the initial stiffness is increased by about 2.5%. Compared with the PSCFSTBP with an external arch steel plate, the lateral bearing capacity, initial stiffness, and energy dissipation capacity are increased by 28.8%, 4.6%, and 13 times, respectively. Compared with the PSCFSTBP without an energy dissipation device, its lateral bearing capacity, initial stiffness, and energy dissipation capacity are increased by 39.4%, 10.4%, and 18 times, respectively. The residual displacement of the PSCFSTBP with an external AEDD is kept within 1 mm in the whole displacement loading stage, the offset rate is less than 1%, and the pier damage is controllable, which can realize rapid repair after an earthquake. Finally, the multi-level energy consumption and local replacement of the AEDD are also explored.

Yttria-stabilized zirconia (YSZ) nanospheres were synthesized by calcination at 900 °C after the adsorption of Y3+ ions into the pores of a zirconium-based metal–organic framework (MOF). The synthesized 3YSZ (zirconia doped with 3 mol% Y2O3), 8YSZ (8 mol% Y2O3), and 30YSZ (30 mol% Y2O3) nanospheres were found to exhibit uniform sizes and shapes. Complex permittivity and complex permeability were carried out in K-band (i.e., 18–26.5 GHz) to determine their suitability for use as low-k materials in 5G communications. The real and imaginary parts of the permittivity of the sintered 3YSZ were determined to be 21.24 and 0.12, respectively, while those of 8YSZ were 22.80 and 0.16, and those of 30YSZ were 7.16 and 0.38. Control of the real part of the permittivity in the sintered YSZ was facilitated by modifying the Y2O3 content, thereby rendering this material an electronic ceramic with potential for use in high-frequency 5G communications due to its excellent mechanical properties, high chemical resistance, and good thermal stability. In particular, it could be employed as an exterior material for electronic communication products requiring the minimization of information loss.

This paper proposes a novel type of steel angle-corrugated steel plate-confined concrete column (SA-CS column). The axial compression behavior of the SA-CS column was investigated by load experiments and finite element (FE) simulation. The study also compared the load–displacement curves, core concrete strength index, and specimens’ ductility indices between the SA-CS columns and concrete-filled steel tube (CFST) columns. The results indicated that the mechanical properties of the SA-CS column were better than those of the CFST column with a similar steel ratio. The rationality and reliability of the finite element model were confirmed by comparing the experimental results’ load–displacement curves and failure modes. Based on the FE model, a supplementary parametric analysis of the effects of the compressive strength of core concrete, thickness, yield strength, and wave height of the corrugated steel plate, thickness, and yield strength of the steel angles was conducted. Moreover, some existing design codes were assessed based on the numerical results available in this study. A new calculating model for the SA-CS column was proposed, which is capable of reasonably predicting the numerical results.

Mesoporous silica-coated multi-branched gold nanoparticles (bAu@mesoSiO2) aiming for enhanced Raman sensing for 4-bromomethcathinone (4-BMC) detection is reported. In this work, we present an effective strategy to probe the Raman signal of 4-MBC. Morphologies and optical properties of the synthesized materials with different [Au3+]/[Au0] ratios are characterized utilizing transmission electron microscopy (TEM), UV–vis and mid-infrared spectroscopy. Both experimental and theoretical (simulation) studies were investigated. Taking advantages of gold core branches that provide highly localized and strongly enhanced electromagnetic fields due to plasmon resonance, surface-enhanced Raman scattering (SERS) is observed. The experimental results show that the SERS intensity exhibits a 100-fold increase with the increased average length and quantity of gold branches (nano tips). The analytical performance yielded a detection limit of 0.1 mg/ml for the 4-MBC target within 5 mins. The sensing method will likely find further improvement and broad use in the forensic science. Besides rapid detection and portability, the combination of the Raman effect and enhanced materials imparts other notable advantages, such as its non-contact and free of reagents. Keywords: Multi-branched gold nanoparticles, SERS, Spectroscopy, 4-Bromomethcathinone, Rapid detection

The clinical efficiency of everolimus, an mammalian target of rapamycin (mTOR) inhibitor, is palliative as sequential or second-line therapy for renal cell carcinoma (RCC). However, the limited response of everolimus in RCC remains uncertain. In the present study, everolimus-resistant RCC models were established to understand the mechanisms and to seek combination approaches. Consequently, the activation of ERK was found to contribute toward everolimus-acquired resistance and poor prognosis in patients with RCC. In addition, the efficacy and mechanism of combination treatment underlying RCC using everolimus and ERK inhibitors was investigated. The ERK inhibitor in combination with everolimus synergistically inhibited the proliferation of RCC cells by arresting the cell cycle in the G1 phase. The combination treatment markedly attenuated the deoxyribonucleoside triphosphate (dNTP) pools by downregulating the mRNA expression of RRM1 and RRM2 through E2F1. The overexpression of E2F1 or supplementation of dNTP rescued the anti-proliferation activity of the everolimus-SCH772984 combination. The antitumor efficacy of combination therapy was reiterated in RCC xenograft models. Thus, the current findings provided evidence that the everolimus-ERK inhibitor combination is a preclinical therapeutic strategy for RCC. Keywords: renal cell carcinoma, ERK inhibitor, everolimus, dNTP, ribonucleotide reductase

Hashing has been widely used for large-scale remote sensing image retrieval due to its outstanding advantages in storage and search speed. Recently, deep hashing methods, which produce discriminative hash codes by building end-to-end deep convolutional networks, have shown promising results. However, training these networks requires numerous labeled images, which are scarce and expensive in remote sensing datasets. In order to solve this problem, we propose a deep unsupervised hashing method, namely deep contrastive self-supervised hashing (DCSH), which uses only unlabeled images to learn accurate hash codes. It eliminates the need for label annotation by maximizing the consistency of different views generated from the same image. More specifically, we assume that the hash codes generated from different views of the same image are similar, and those generated from different images are dissimilar. On the basis of the hypothesis, we can develop a novel loss function containing the temperature-scaled cross-entropy loss and the quantization loss to train the developed deep network end-to-end, resulting in hash codes with semantic similarity preserved. Our proposed network contains four parts. First, each image is transformed into two different views using data augmentation. After that, they are fed into an encoder with the same shared parameters to obtain deep discriminate features. Following this, a hash layer converts the high-dimensional image representations into compact binary codes. Lastly, a novel hash function is introduced to train the proposed network end-to-end and thus guide generated hash codes with semantic similarity. Extensive experiments on two popular benchmark datasets of the UC Merced Land Use Database and the Aerial Image Dataset have demonstrated that our DCSH has significant superiority in remote sensing image retrieval compared with state-of-the-art unsupervised hashing methods.

Objective To investigate the factors involved in early and mid-term complications after catheter insertion for peritoneal dialysis and to establish prediction models. Methods A total of 158 patients with peritoneal dialysis in the Department of Nephrology of our hospital were retrospectively analyzed. General information, laboratory indices, early complications (within 1 month after the operation), mid-term complications (1–6 months after the operation), and other relevant data were recorded. Multivariate logistic regression analysis was performed to establish a prediction model of complications and generate a nomogram. Receiver operating characteristic (ROC) curve analysis was used to evaluate the efficacy of the model. Results Among the patients, 48 (30.8%) had early complications, which were mainly catheter-related complications, and 29 (18.4%) had mid-term complications, which were mainly abdominal infection and catheter migration. We constructed a prediction model for early complications (area under the curve = 0.697, 95% confidence interval: 0.609–0.785) and mid-term complications (area under the curve = 0.730, 95% confidence interval: 0.622–0.839). The sensitivity was 0.750 and 0.607, and the specificity was 0.589 and 0.765, respectively. Conclusions Our prediction model has clinical significance for risk assessment of early and mid-term complications and prevention of complications after catheterization for peritoneal dialysis.

In order to develop a new type of prefabricated bridge structure system with green, efficient and recoverable function, which complies with the new requirements of rapid repair of pier function after earthquake, and improves the applicable performance of prefabricated assembled pier in medium and high-intensity seismic areas, a precast segmental concrete-filled steel tubular (PSCFST) pier with an external energy dissipation ring is proposed. Based on ABAQUS analysis software, a four-segment PSCFST pier model is established, and the pseudo-static comparative analysis is carried out between the traditional PSCFST pier and the PSCFST pier with the external energy dissipation ring. The results show that compared with the traditional PSCFST pier, the lateral bearing capacity of the PSCFST pier with an external energy dissipation ring is increased by 60%, the energy dissipation capacity is increased by about 20 times, and the damage is concentrated in the energy dissipation ring, the damage is controllable, and the rapid repair after the earthquake can be realized by replacing energy dissipation devices and other measures. At the same time, the seismic performance of pier models with three different control parameters (initial prestress, material strength of energy dissipation ring and section width of energy dissipation ring) under reciprocating loading is analyzed. The results show that the initial prestress does not affect the cumulative energy consumption of the pier; the increase in the material strength of the energy dissipation ring improves the overall stiffness and improves the energy dissipation capacity of the PSCFST pier; the reduction in section width will affect the overall equivalent stiffness and unloading stiffness of the segmental pier, and the energy dissipation capacity will be significantly reduced.

Ultrasonic nanocrystal surface modification (UNSM) was applied to hot-rolled Mg-Li alloys (LAE361 and LA106). The microstructure, mechanical properties, deformation mechanisms, and corrosion resistance properties of these alloys after UNSM treatment were systematically studied. Significant improvement in surface hardness and decrease in surface roughness were achieved by UNSM treatment. Meanwhile, the basal texture intensity of the Mg-Li alloys reduced significantly, and several deformation twins appeared on the surface layer. The α phase of the surface layer underwent twin deformation and basal plane slip. The fibre textures in the β phase of LA106 Mg-Li alloy changed from γ and η to α and ε, which mainly resulted in the dislocation slip. More importantly, UNSM treatment exhibited enhanced strength and improved plasticity of LAE361 and LA106 Mg-Li alloys. The corrosion current density of LAE361 Mg-Li alloy reduced approximately 29.3% by UNSM treatment, while it increased the corrosion current density of LA106 Mg-Li alloy by 189.7%. These studies show that the application of UNSM to improve the corrosion resistance of duplex phases of LA106 Mg-Li alloy needs further investigation.

Coffee, one of the most popular beverages in the world, attracts consumers by its rich aroma and the stimulating effect of caffeine. Increasing consumers prefer decaffeinated coffee to regular coffee due to health concerns. There are some main decaffeination methods commonly used by commercial coffee producers for decades. However, a certain amount of the aroma precursors can be removed together with caffeine, which could cause a thin taste of decaffeinated coffee. To understand the difference between regular and decaffeinated coffee from the volatile composition point of view, headspace solid-phase microextraction two-dimensional gas chromatography time-of-flight mass spectrometry (HS-SPME-GC×GC-TOFMS) was employed to examine the headspace volatiles of eight pairs of regular and decaffeinated coffees in this study. Using the key aroma-related volatiles, decaffeinated coffee was significantly separated from regular coffee by principal component analysis (PCA). Using feature-selection tools (univariate analysis: t-test and multivariate analysis: partial least squares-discriminant analysis (PLS-DA)), a group of pyrazines was observed to be significantly different between regular coffee and decaffeinated coffee. Pyrazines were more enriched in the regular coffee, which was due to the reduction of sucrose during the decaffeination process. The reduction of pyrazines led to a lack of nutty, roasted, chocolate, earthy, and musty aroma in the decaffeinated coffee. For the non-targeted analysis, the random forest (RF) classification algorithm was used to select the most important features that could enable a distinct classification between the two coffee types. In total, 20 discriminatory features were identified. The results suggested that pyrazine-derived compounds were a strong marker for the regular coffee group whereas furan-derived compounds were a strong marker for the decaffeinated coffee samples.

Many cancer risk loci act as expression quantitative trait loci (eQTLs) of transcripts including non-coding RNA. Long non-coding RNAs (lncRNAs) are implicated in various human cancers. However, the pathological and clinical impacts of the genetic determinants of lncRNAs in cancers remain largely unknown. In this study, we performed eQTL mapping of lncRNA expression (elncRNA) in 11 TCGA cancer types and characterized the biological processes of elncRNAs in the setting of genomic location, cancer treatment responses, and immune microenvironment. As a result, 10.86% of the cis-eQTLs and 1.67% of the trans-eQTLs of lncRNA were related to known genome-wide association studies (GWAS) cancer risk loci. The elncRNAs are significantly enriched for those which are previously annotated as predictive of drug sensitivities in cancer cell lines. We further revealed the downstream transcriptomic effectors of eQTL-elncRNA pairs. Our data specifically suggested that the genes affected by eQTL-elncRNA associations are enriched in the immune system processes and eQTL-elncRNA associations influence the constitution of tumor infiltrating lymphocytes. In ovarian cancer, the “rs34631313-AC092580.4” pair was associated with increased fraction of CD8+ T cells and M1 Macrophage; whereas in KIRC, the “rs9546285-LINC00426” pair was associated with increased fraction of CD8+ T cells and a decreased fraction of M2 macrophages. Our findings provide a systematic view of the transcriptomic impacts of the eQTL landscape of lncRNA in human cancers and suggest its strong potential relevance to cancer immunity and treatment.

Due to the increasing prevalence of pathogenic fungal infections, the emergence of antifungal resistant clinical isolates worldwide, and the limited arsenal of available antifungals, developing new antifungal strategies is imperative. In this study, we screened a library of 1068 FDA-approved drugs to identify hits that exhibit broad-spectrum antifungal activity. Robenidine, an anticoccidial agent which has been widely used to treat coccidian infections of poultry and rabbits, was identified in this screen. Physiological concentration of robenidine (8 μM) was able to significantly inhibit yeast cell growth, filamentation and biofilm formation of Candida albicans – the most extensively studied human fungal pathogen. Moreover, we observed a broad-spectrum antifungal activity of this compound against fluconazole resistant clinical isolates of C. albicans, as well as a wide range of other clinically relevant fungal pathogens. Intriguingly, robenidine-treated C. albicans cells were hypersensitive to diverse cell wall stressors, and analysis of the cell wall structure by transmission electron microscopy (TEM) showed that the cell wall was severely damaged by robenidine, implying that this compound may target the cell wall integrity signaling pathway. Indeed, upon robenidine treatment, we found a dose dependent increase in the phosphorylation of the cell wall integrity marker Mkc1, which was decreased after prolonged exposure. Finally, we provide evidence by RNA-seq and qPCR that Rlm1, the downstream transcription factor of Mkc1, may represent a potential target of robenidine. Therefore, our data suggest that robenidine, a FDA approved anti-coccidiosis drug, displays a promising and broadly effective antifungal strategy, and represents a potentially repositionable candidate for the treatment of fungal infections.

Chlorinated paraffins (CPs) are industrial chemicals that are produced in large quantities and used globally. Human exposure to CPs is primarily through dietary intake, especially from animal-derived food products. Even so, there is little information regarding CP concentrations in dairy products. In this study, raw samples of cow milk were collected from various regions in China within the Neimenggu (n = 10), Hebei (n = 9), Shandong (n = 10), Henan (n = 10) and Hubei (n = 9) provinces. The mean concentrations of short chain CPs (SCCPs) and medium chain CPs (MCCPs) in the milk samples from industrial areas (1670 and 190 ng/g lipid, respectively) were higher than those from non-industrial areas (490 and 72 ng/g lipid, respectively). In most samples, C10H16Cl6 and C14H23Cl7 were the primary SCCP and MCCP congener groups, respectively. The mean concentrations of SCCPs and MCCPs in dairy cow feed (silage) were determined to be 750 and 36 ng/g dry weight, respectively. The SCCP and MCCP congener group patterns in the milk were similar to those in the silage, indicating that animal feed intake might be an important pathway for the exposure of dairy cows to CPs. Thus, the ingestion of CPs by humans through dairy products should not be neglected and the contamination of animal feed by CPs should be considered. Keywords: Chlorinated paraffins, Milk, Silage, Pollution, Cow

Purpose - Freeway work zones have been traffic bottlenecks that lead to a series of problems, including long travel time, high-speed variation, driver’s dissatisfaction and traffic congestion. This research aims to develop a collaborative component of connected and automated vehicles (CAVs) to alleviate negative effects caused by work zones. Design/methodology/approach - The proposed cooperative component is incorporated in a cellular automata model to examine how and to what scale CAVs can help in improving traffic operations. Findings - Simulation results show that, with the proposed component and penetration of CAVs, the average performances (travel time, safety and emission) can all be improved and the stochasticity of performances will be minimized too. Originality/value - To the best of the authors’ knowledge, this is the first research that develops a cooperative mechanism of CAVs to improve work zone performance.