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Self-assembling peptides, offering favorable biocompatibility, high stability, and easy incorporation of various functionalities, have demonstrated enormous potential for the precise design of next-generation nanodrugs for non-invasive tumor therapy. Peptide-based supramolecular photodynamic therapy (PDT) has shown great promise as an emerging modality for cancer treatment, achieving substantially-enhanced photosensitizer delivery selectivity and treatment efficacy, based on peptide biological activity and self-assembly potential. Although considerable research has been conducted toward fabricating self-assembling peptide-based smart nanodrugs for PDT, few studies have investigated cellular biophysical responses as indicators of tumor function and metabolic state. Here, via atomic force microscopy (AFM)-based morphological and mechanical measurements, including optical microscopy and scanning electron microscopy, we observed, for the first time, variation in membrane stiffness of human liver (HepG2) cancer cells treated with self-assembling peptides serving as a PDT nanodrug. This biophysical information will help to establish a comprehensive understanding of the anticancer effect of peptide-based smart nanodrugs, and highlight the exceptional ability of AFM in determining cell-surface properties., (© 2023 IOP Publishing Ltd.)

Introduction: While living donor (LD) kidney transplantation is the optimal treatment for patients with kidney failure, LDs assume a higher risk of future kidney failure themselves. LDs of African ancestry have an even greater risk of kidney failure post-donation than White LDs. Because evidence suggests that Apolipoprotein L1 ( APOL1 ) risk variants contribute to this greater risk, transplant nephrologists are increasingly using APOL1 genetic testing to evaluate LD candidates of African ancestry. However, nephrologists do not consistently perform genetic counselling with LD candidates about APOL1 due to a lack of knowledge and skill in counselling. Without proper counselling, APOL1 testing will magnify LD candidates' decisional conflict about donating, jeopardising their informed consent. Given cultural concerns about genetic testing among people of African ancestry, protecting LD candidates' safety is essential to improve informed decisions about donating. Clinical 'chatbots', mobile apps that provide genetic information to patients, can improve informed treatment decisions. No chatbot on APOL1 is available and no nephrologist training programmes are available to provide culturally competent counselling to LDs about APOL1 . Given the shortage of genetic counsellors, increasing nephrologists' genetic literacy is critical to integrating genetic testing into practice., Methods and Analysis: Using a non-randomised, pre-post trial design in two transplant centres (Chicago, IL, and Washington, DC), we will evaluate the effectiveness of culturally competent APOL1 testing, chatbot and counselling on LD candidates' decisional conflict about donating, preparedness for decision-making, willingness to donate and satisfaction with informed consent and longitudinally evaluate the implementation of this intervention into clinical practice using the R each, E ffectiveness, A doption, I mplementation and M aintenance framework., Ethics and Dissemination: This study will create a model for APOL1 testing of LDs of African ancestry, which can be implemented nationally via implementation science approaches. APOL1 will serve as a model for integrating culturally competent genetic testing into transplant and other practices to improve informed consent. This study involves human participants and was approved by Northwestern University IRB (STU00214038). Participants gave informed consent to participate in the study before taking part., Trial Registration: ClinicalTrials.gov Identifier: NCT04910867. Registered 8 May 2021, https://register., Clinicaltrials: gov/prs/app/action/SelectProtocol?sid=S000AWZ6&selectaction=Edit&uid=U0001PPF&ts=7&cx=-8jv7m2 ClinicalTrials.gov Identifier: NCT04999436. Registered 5 November 2021, https://register., Clinicaltrials: gov/prs/app/action/SelectProtocol?sid=S000AYWW&selectaction=Edit&uid=U0001PPF&ts=11&cx=9tny7v., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Fluorosis causes female reproductive dysfunction with reduced fertility without established pathogenesis. To clarify the mechanism, Sprague-Dawley female rats were selected with drinking water containing 0, 50 (low), 100 (moderate), and 150 mg/L (high) sodium fluoride (NaF) for a short (2 months), medium (4 months), and long term (6 months). The water consumption and body weight of female rats were recorded daily. The effect of NaF on the estrous cycle was examined by vaginal smears and recorded in different term treatments. Female and male rats were mated in a 2:1 ratio for 1 week at 2-, 4-, and 6-month treatment time for mating performance and fertility rate. Selected female rats were executed for tissue and blood collection at different treatment terms. Twenty-four-hour urine sample from each female rat was collected using the metabolic cage. The levels of steroid hormones and silent information regulator 2 homolog 1 (SIRT1) in serum were measured by appropriate ELISA kits. Body weight of the high NaF group was significantly less during short-term treatment than that of other treatment groups or control group. Urinary fluoride concentration was increased linearly with treatment time. Treatment of NaF significantly decreased steroid hormone level while increased SIRT1 level in the serum. In addition, NaF treatment significantly decreased pregnancy rate. It is concluded that NaF inhibits the secretion of hormone and estradiol (E 2 ) release from the ovary, thereby reducing the rate of pregnant. SIRT1 may be involved in this NaF-induced reproductive dysfunction in female rats through regulating reproductive hormone, FSH, and LH secretion., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Transformers have made remarkable progress towards modeling long-range dependencies within the medical image analysis domain. However, current transformer-based models suffer from several disadvantages: (1) existing methods fail to capture the important features of the images due to the naive tokenization scheme; (2) the models suffer from information loss because they only consider single-scale feature representations; and (3) the segmentation label maps generated by the models are not accurate enough without considering rich semantic contexts and anatomical textures. In this work, we present CASTformer, a novel type of adversarial transformers, for 2D medical image segmentation. First, we take advantage of the pyramid structure to construct multi-scale representations and handle multi-scale variations. We then design a novel class-aware transformer module to better learn the discriminative regions of objects with semantic structures. Lastly, we utilize an adversarial training strategy that boosts segmentation accuracy and correspondingly allows a transformer-based discriminator to capture high-level semantically correlated contents and low-level anatomical features. Our experiments demonstrate that CASTformer dramatically outperforms previous state-of-the-art transformer-based approaches on three benchmarks, obtaining 2.54%-5.88% absolute improvements in Dice over previous models. Further qualitative experiments provide a more detailed picture of the model's inner workings, shed light on the challenges in improved transparency, and demonstrate that transfer learning can greatly improve performance and reduce the size of medical image datasets in training, making CASTformer a strong starting point for downstream medical image analysis tasks.

Many medical datasets have recently been created for medical image segmentation tasks, and it is natural to question whether we can use them to sequentially train a single model that (1) performs better on all these datasets, and (2) generalizes well and transfers better to the unknown target site domain. Prior works have achieved this goal by jointly training one model on multi-site datasets, which achieve competitive performance on average but such methods rely on the assumption about the availability of all training data, thus limiting its effectiveness in practical deployment. In this paper, we propose a novel multi-site segmentation framework called incremental-transfer learning (ITL) , which learns a model from multi-site datasets in an end-to-end sequential fashion. Specifically, "incremental" refers to training sequentially constructed datasets, and "transfer" is achieved by leveraging useful information from the linear combination of embedding features on each dataset. In addition, we introduce our ITL framework, where we train the network including a site-agnostic encoder with pretrained weights and at most two segmentation decoder heads. We also design a novel site-level incremental loss in order to generalize well on the target domain. Second, we show for the first time that leveraging our ITL training scheme is able to alleviate challenging catastrophic forgetting problems in incremental learning. We conduct experiments using five challenging benchmark datasets to validate the effectiveness of our incremental-transfer learning approach. Our approach makes minimal assumptions on computation resources and domain-specific expertise, and hence constitutes a strong starting point in multi-site medical image segmentation.

Fluorosis often causes female reproductive dysfunction. A rapid turnover of DNA methylation is a pathological change in many human diseases, including female reproductive dysfunction. The role of DNA methylation in fluorosis was unknown and investigated in this experiment. Fifty fluorosis women patients were selected as High F group and forty-six healthy women were recruited as Control group were enrolled. In addition, ovarian granulosa cells were obtained from five women in High F group and five women in Control group. All ten women went through in vitro fertilization (IVF) process with DNA methylation sequencing. KGN cells (human granulosa cell line) were cultured with different concentrations of sodium fluoride (0-8 mM NaF) for 24 h for the in vitro study. The level of DNA methylation in blood samples was significantly higher in High F group than that in Control group. The level of serum estradiol (E 2 ) was significantly lower in women from High F group, while the levels of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in High F group were significantly higher than that in Control group. The methylation sequences of KGN cells relating to autophagy were significantly changed by NaF treatment dose-dependently. Based on these results, it is concluded that DNA methylation and autophagy may play a significant role in the pathophysiology of reproductive dysfunction caused by fluorosis., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Coral trees ( Viburnum odoratissimum ), as a class of evergreen shrubs, are mainly planted in landscapes in numerous cities in China. During September 2020, the author investigated four major parks in Hefei (Bao Park, Hefei Botanical Garden, Luzhou Park and Peninsula Park) and the campus of Anhui Agricultural University (approximately 0.5 ha) (31°49'21.30″N, 117°13'18.25″E). The results showed that the incidence rate of leaf spot disease reached 60% among approximately 100,000 coral trees planted in these areas. Coral trees begin to show leaf spots in August. In early stages of coral trees infection, the symptoms appeared as small brown spots ranged in length from 2 to 3 millimeters on the leaves. After the disease patches expand and darken, the coral leaves eventually wither and fall, which seriously affects its viewing and admiring value. To identify the fungal pathogen, the five-point sampling method was used to take typical similar leaf samples from 5 regions, and 6 samples were taken from each site, so a total of 150 samples were obtained. Fragments of sample leaves were surface-sterilized with 1% NaClO, plated on potato dextrose agar, and incubated at 25 °C in the dark. A total of 275 strains were obtained from 150 samples. According to the morphological characteristics, 275 strains were purified and divided into four types. Four representative strains (MI1, K1, F1, D1) were selected from four types for further pathogenicity testing and identification. The pathogenicity test was conducted in triplicate by inoculating wounded leaves of 1-year-old potted V. odoratissimum with 20μL of a conidial suspension (10 6 conidia/mL). The control was inoculated with sterile water. The specimens were placed in a growth chamber while maintaining 90% relative humidity and 28℃. After five days, the characteristic lesions were observed only on inoculated MI1 spore suspension leaves. The same fungus was reisolated from the lesions, thus fulfilling Koch's postulates. The pathogenic fungi accounted for 60% of all strains. Fungal colonies were circular and had abundant white aerial mycelium, and colonies changed from white to pure black after maturity. Conidia were fusiform (16-17×5-6 μm), thin-walled, transparent, and without diaphragms. Molecular identification was performed by partially sequencing the internal transcribed spacer (ITS) gene, the translation elongation Factor 1-alpha(EF1-alpha) gene, and the β-tubulin (TUB2) gene by using the primers ITS1/ITS4 (White et al. 1990), EF1-728F (Alves et al. 2008)/EF1-986R (Carbone & Kohn 1999), and Bt2a/Bt2b (Glass & Donaldson 1995), respectively. The obtained ITS sequence (MW767713) showed 99% identity with N. parvum CMW28429 (KU997429.1), the EF1-alpha sequence (MZ398261) showed 99% identity with N. parvum isolate A4 (FJ528597.1), and the TUB2 sequence (MZ398260) showed 99% identity with N. parvum isolate BO52 (KU554657.1). By combining the sequences of individual fragments of each fungus in the order ITS, EF1-alpha and TUB2, MEGA 6.0 was used to analyze the sequence of kinship by using the maximum likelihood method, and the repeat value of bootstraps was 1000. A polygenic phylogenetic tree analysis based on multilocus alignment (ITS, EF1-alpha and TUB2) was constructed with some strains of Botryosphaeriaceae species. The results of the phylogenetic tree showed that MI1 and N. parvum clustered into a branch. To our knowledge, this is the first report of N. parvum causing leaf spot on V. odoratissimum in China.

Introduction: Selective mediastinal lymphadenectomy (SML) and complete mediastinal lymphadenectomy (CML) are two main types of surgery conducted for the treatment of non-small cell lung cancer (NSCLC) plus lobectomy or segmentectomy. It is not known whether stage I NSCLC can benefit from CML. Using the meta-analytical method, our research aimed to find out the worth of SML and CML for the therapy of clinical stage I NSCLC., Methods: We searched PubMed, Ovid, MEDLINE, Cochrane Controlled Trial Register (CENTRAL), Embase, and Google Scholar for literature published up to June 2021 to evaluate the comparative research and to assess the post-operative complications, overall survival rate, disease-free survival rate, and local and distant recurrence. This meta-analysis was conducted by combining the results of the reported incidences of post-operative complications, local and distant recurrence, and short- and long-term mortality. The pooled odds ratios (OR) and the 95% confidence intervals were calculated by random or fixed effects models to compare the effectiveness between these two methods., Results: Five retrospective studies and one randomized controlled trial study were included in our research. The six studies included a total of 5713 patients, of whom 1480 were assigned to the SML group and 4233 were assigned to the CML group. No statistically significant differences were found in the 1- and 5-year overall survival rates or the 1-, 3-, and 5-year disease-free survival rates between the two groups. However, the 3-year overall survival favored the SML group (P < 0.05). There were also no statistically significant differences between the local and distant metastasis. Among the postoperative complications, pneumonia, atelectasis, and prolonged air leak were more common in the CML group (P < 0.05). There were no differences in the prevalence of dysrhythmia, chylothorax, acute respiratory distress syndrome, or recurrent laryngeal nerve injury between the two groups, which may be due to the limited sample size., Conclusion: Considering the comparable survival rates, disease control, and fewer postoperative complications in the evaluated participants, SML is the preferred treatment with less invasiveness for clinical stage I NSCLC., (© 2021. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Common to most medical imaging techniques, the spatial resolution of Magnetic Resonance Spectroscopic Imaging (MRSI) is ultimately limited by the achievable SNR. This work presents a deep learning method for 1H-MRSI spatial resolution enhancement, based on the observation that multi-parametric MRI images provide relevant spatial priors for MRSI enhancement. A Multi-encoder Attention U-Net (MAU-Net) architecture was constructed to process a MRSI metabolic map and three different MRI modalities through separate encoding paths. Spatial attention modules were incorporated to automatically learn spatial weights that highlight salient features for each MRI modality. MAU-Net was trained based on in vivo brain imaging data from patients with high-grade gliomas, using a combined loss function consisting of pixel, structural and adversarial loss. Experimental results showed that the proposed method is able to reconstruct high-quality metabolic maps with a high-resolution of 64×64 from a low-resolution of 16 × 16, with better performance compared to several baseline methods.

Abstract: Pepsinogen (PG) I and II are crucial in the gastric digestive processes. This study is to examine the relationship of serum PGI, PGII, and PGI/PGII ratio with Helicobacter pylori (Hp) infection, age, sex, and body mass index (BMI) in subjects in Beijing, China.A total of 40,383 asymptomatic subjects, who underwent medical examination in Beijing Rehabilitation Hospital, were included in this study. Serum PG levels were measured using chemoluminescence techniques. The age, sex, and BMI data were collected, and Hp infection was identified with 13C-urea breath test. Statistical analysis was conducted with Python, Pandas and Seaborn software.Asymptomatic subjects with Hp infection (Hp+) had a significantly higher level of PGI in the serum (111 ng/mL [median]) than those without Hp infection (Hp-) (94 ng/mL, P < .001). The asymptomatic Hp+ subjects had 2-fold higher PGII levels (7.2 ng/mL) than Hp- subjects (3.2 ng/mL, P < .001). These changes produced significantly lower PGI/II ratio in Hp+ patients than in Hp- subjects (16:30, P < .001). The serum PGI and PGII levels were higher in males than in females (PGI: 104 ng/mL vs 95 ng/mL, PGII: 4.3 ng/mL vs 3.7 ng/mL, both P < .001), PGI/II ratio of males is at 95% of that in females (P < .001). PGI and PGII levels gradually increased in older people (P < .001), whereas the PGI/II ratio decreased significantly with age (P < .001). The levels of the two serum PGs were decreased and the ratio increased when BMI were higher than 28 kg/cm2 (P < .05).The levels of serum PGI, especial PGII, were increased by Hp infection, and also influenced by age, sex, and BMI. Therefore, these influencing factors should be considered during clinical practice., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Membrane-based gas separation exhibits many advantages over other conventional techniques; however, the construction of membranes with simultaneous high selectivity and permeability remains a major challenge. Herein, (LDH/FAS) n -PDMS hybrid membranes, containing two-dimensional sub-nanometre channels were fabricated via self-assembly of unilamellar layered double hydroxide (LDH) nanosheets and formamidine sulfinic acid (FAS), followed by spray-coating with a poly(dimethylsiloxane) (PDMS) layer. A CO 2 transmission rate for (LDH/FAS) 25 -PDMS of 7748 GPU together with CO 2 selectivity factors (SF) for SF(CO 2 /H 2 ), SF(CO 2 /N 2 ) and SF(CO 2 /CH 4 ) mixtures as high as 43, 86 and 62 respectively are observed. The CO 2 permselectivity outperforms most reported systems and is higher than the Robeson or Freeman upper bound limits. These (LDH/FAS) n -PDMS membranes are both thermally and mechanically robust maintaining their highly selective CO 2 separation performance during long-term operational testing. We believe this highly-efficient CO 2 separation performance is based on the synergy of enhanced solubility, diffusivity and chemical affinity for CO 2 in the sub-nanometre channels.

Excessive intake of fluoride may cause female reproductive dysfunction but pathological mechanism is unclear. The miRNAs in follicular fluid are a class of small non-coding RNAs from granulosa cells. The aim of this study is to examine the differential expressions of miRNAs in ovarian granulosa cells from women suffering from fluorosis and infertility. Five fluorosis women suffering infertility and 5 non-fluorosis (normal ovarian secretory function control) women were included as two groups. These two groups were indexed by serum and urine fluoride (F) levels as high F group and control group. The concentrations of estradiol (E 2 ), progesterone (P), human chorionic gonadotropin (HCG), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured by ELISA kits. The characteristics of menstruation from each woman were collected. The total RNA was isolated from granulosa cells for sequencing. The validation was completed by RT-qPCR. There was no significant difference between the two groups on age, the levels of E 2 , FSH, P, HCG, and LH in serum, and the characteristics of menstruation. A total of 37 miRNAs were upregulated and 40 miRNAs downregulated in follicular fluid from granulosa cells in the high F group compared with that in the control group. The expression of hsa-miR-29b increased in fluorosis patients identified by the miRNA sequence analysis. The distinct expression patterns of miRNAs in women requiring IVF from fluorosis area provide a new direction for molecular mechanism of fluorosis caused reproductive dysfunction.

Lung cancer continues to be one of the leading causes of cancer-related mortality worldwide and its incidence is still increasing. With aging population and development in imaging technology, many more elderly with early-stage lung cancers are being diagnosed than in the past. Lobectomy and sub-lobar resection are two main surgical approach for the treatment for this kind of patients. This review aimed to compare these two methods for this hot issue.

Wip1 is deregulated in numerous human malignancies. However, its roles in non‑small cell lung cancer (NSCLC) remain unclear. In the current study, the expression of Wip1 was investigated in NSCLC and its clinical significance was detected. Immunohistochemical staining was used to measure the expression of (wild‑type p53 induced phosphatase 1) Wip1, p38 mitogen‑activated protein kinase (MAPK), p53, p16 protein in a group of 60 NSCLC and 20 normal lung tissues. In addition, western blotting was performed to detect the Wip1 protein in fresh tissues. The correlations between clinical characteristics and Wip1 expression were analyzed using SPSS, version 16.0 software. The expression of Wip1 was positive in 63.3% (38/60) of NSCLC tissues, and in none of the normal lung tissues (0/20; P<0.01). In addition, Wip1 overexpression was significantly associated with tumor length and differentiation (P=0.008 and 0.03, respectively). The expression of Wip1 was negatively correlated with that of p38MAPK, p53 and p16 (r=‑0.284, ‑0.352 and ‑0.348, respectively). The results of the current study demonstrated that Wip1 was frequently overexpressed in NSCLC, which may serve an essential role in the p38MAPK/p53/p16 signaling pathway.

We previously demonstrated that gammadelta T cells played an important role in tumor immune surveillance by providing an early source of IFN-gamma. The precise role of different subsets of gammadelta T cells in the antitumor immune response, however, is unknown. Vgamma1 and Vgamma4 gammadelta T cells are the principal subsets of peripheral lymphoid gammadelta T cells and they might play distinct roles in tumor immunity. In support of this, we observed that reconstitution of TCRdelta(-/-) mice with Vgamma4, but not Vgamma1, gammadelta T cells restored the antitumor response. We also found that these effects were exerted by the activated (CD44(high)) portion of Vgamma4 gammadelta T cells. We further determined that IFN-gamma and perforin are critical elements in the Vgamma4-mediated antitumor immune response. Indeed, CD44(high) Vgamma4 gammadelta T cells produced significantly more IFN-gamma and perforin on activation, and showed greater cytolytic activity than did CD44(high) Vgamma1 gammadelta T cells, apparently due to the high level of eomesodermin (Eomes) in these activated Vgamma4 gammadelta T cells. Consistently, transfection of dominant-negative Eomes in Vgamma4 gammadelta T cells diminished the level of IFN-gamma secretion, indicating a critical role of Eomes in the effector function of these gammadelta T cells. Our results thus reveal distinct functions of Vgamma4 and Vgamma1 gammadelta T cells in antitumor immune response, and identify a protective role of activated Vgamma4 gammadelta T cells, with possible implications for tumor immune therapy.