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PurposeTo explore fecal immune-related proteins that can be used for colorectal cancer (CRC) diagnosis.Patients and methodsThree independent cohorts were used in present study. In the discovery cohort, which included 14 CRC patients and 6 healthy controls (HCs), label-free proteomics was applied to identify immune-related proteins in stool that could be used for CRC diagnosis. Exploring potential links between gut microbes and immune-related proteins by 16S rRNA sequencing. The abundance of fecal immune-associated proteins was verified by ELISA in two independent validation cohorts and a biomarker panel was constructed that could be used for CRC diagnosis. The validation cohort I included 192 CRC patients and 151 HCs from 6 different hospitals. The validation cohort II included 141 CRC patients, 82 colorectal adenoma (CRA) patients, and 87 HCs from another hospital. Finally, the expression of biomarkers in cancer tissues was verified by immunohistochemistry (IHC).ResultsIn the discovery study, 436 plausible fecal proteins were identified. And among 67 differential fecal proteins (|log2 fold change| > 1, P< 0.01) that could be used for CRC diagnosis, 16 immune-related proteins with diagnostic value were identified. The 16S rRNA sequencing results showed a positive correlation between immune-related proteins and the abundance of oncogenic bacteria. In the validation cohort I, a biomarker panel consisting of five fecal immune-related proteins (CAT, LTF, MMP9, RBP4, and SERPINA3) was constructed based on the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. The biomarker panel was found to be superior to hemoglobin in the diagnosis of CRC in both validation cohort I and validation cohort II. The IHC result showed that protein expression levels of these five immune-related proteins were significantly higher in CRC tissue than in normal colorectal tissue.ConclusionA novel biomarker panel consisting of fecal immune-related proteins can be used for the diagnosis of CRC.

Chimeric antigen receptor (CAR) T-cell therapy has made remarkable progress in cancer immunotherapy, but several challenges with unclear mechanisms hinder its wide clinical application. Single-cell sequencing technologies, with the powerful unbiased analysis of cellular heterogeneity and molecular patterns at unprecedented resolution, have greatly advanced our understanding of immunology and oncology. In this review, we summarize the recent applications of single-cell sequencing technologies in CAR T-cell therapy, including the biological characteristics, the latest mechanisms of clinical response and adverse events, promising strategies that contribute to the development of CAR T-cell therapy and CAR target selection. Generally, we propose a multi-omics research mode to guide potential future research on CAR T-cell therapy.

BackgroundTrichilemmal carcinoma (TLC) is a rare malignant cutaneous adnexal neoplasm, with no relatively comprehensive research.ObjectiveThe aim of this study is to perform an updated statistical analysis so as to better understand TLC’s epidemiology, clinical features, diagnosis, and treatment.MethodsThe diagnosis and treatment of three TLC cases in our department were summarized. Then, all TLC cases published in the literature were retrieved for a comprehensive analysis, followed by the analysis of global trends and regional distribution, demographic characteristics, clinical features, pathogenesis, histopathological features, and treatment and prognosis of TLC.ResultsOf the 231 cases, the incidence of TLC has shown an upward trend recently, especially in China, in Asia. The susceptible population is men aged 60–80 and women over 80, and the most prone location is head and neck. The phenotype of TLC is not always typical and may be misdiagnosed because of the coexistence of other diseases. There is a linear relationship between the diameter and its duration or thickness. UV, locally present skin lesions, trauma, scarring, organ transplantation, and genetic disorders may trigger the occurrence of TLC. Periodic acid–Schiff staining and CD34, but not Epithelial Membrane Antigen (EMA), were helpful in the diagnosis of TLC. Although effective, surgical excision and Mohs micrographic surgery need further improvement to reduce recurrence of TLC. Carcinoma history is an independent risk factor for TLC recurrence.LimitationsThe limitation of this study is the lack of randomized controlled trial on TLC treatment and recurrence.ConclusionTLC has the possibility of invasive growth and recurrence, especially in patients with longer duration and carcinoma history.

Allogeneic anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has the potential for extensive clinical applications. This study aimed to evaluate its efficacy and safety in treating relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). Four databases were searched for relevant studies. Among patients treated with donor-derived CAR T-cell therapy, ALL patients had a complete remission (CR) rate of 80 % and a 1-year overall survival rate of 51 %. The graft-versus-host disease (GvHD) rate was 4 %, cytokine release syndrome was 69 %, and immune effector cell-associated neurotoxicity syndrome was 8 %. For off-the-shelf CAR T-cell therapy, the CR rate for ALL was 70 %, and for NHL, it was 52 %. The objective response rate for NHL was 72 %. The pooled GvHD of off-the-shelf CAR T-cell therapy for ALL and NHL combined was 0 %. Allogeneic anti-CD19 CAR T-cell therapy are effective and safe for treating R/R ALL and NHL. AVAILABILITY OF DATA AND MATERIALS: All datasets generated in this study are included in the article/Supplementary Material.

Background This study aimed to classify relapsed retroperitoneal liposarcoma (RLS) as new primary (NP) or true recurrence (TR) and to assess the implications for therapeutic management of these classifications. Methods Patients with recurrent RLS were classified as NP if the relapse was different from the former tumor’s pathology subtype and anatomical location. Kaplan-Meier curves were adapted to estimate relapse-free survival (RFS), and logistic regression analysis was used to explore the factors related to NP.Results Total 177 patients with relapsed RLS were included in this study. The median tumor sizes were 16 cm (IQR, 13-22 cm, NP) and 18 cm (IQR, 12-25 cm, TR) (P=0.003). Multifocal tumors (89.2% vs 73.8%, P=0.011) and multiple pathology subtypes (52.7% vs 31.1%, P=0.004) were more common in the NP group and tended to invade wider anatomical areas (85.1% vs 71.8%, P=0.037). The median RFS was 17 months (IQR, 7-35 months) in the NP group and 12 months (IQR, 5-23 months) in the TR group, and NP patients showed a longer RFS than TR patients (P=0.004). When the log-rank test was conducted, low-grade pathology, tumor growth rate ≤ 1.25 cm/month and tumor size ≤ 16.5 cm had a significant influence on the NP phenomenon (P=0.015, 0.019, and 0.028, respectively). Logistic regression analysis illustrated that current surgeries, pathology subtype varieties and pathology grade were independent risk factors for NP (P=0.017, 0.019, and 0.025, respectively).Conclusion NP patients have longer RFS than TR patients, and their tumors tend to have multiple pathology subtypes and tumors and are more likely to invade wider anatomical areas. This classification contributes to a better understanding of RLS and provides new evidence for different therapeutic management of relapsed tumors.

We theoretically propose a high-efficiency tunable metalens based on an ellipse-shaped perforated graphene metasurface. By optimizing the axial length ratio of the elliptical aperture, we find the elliptical aperture with high reflectivity over a broad band by means of observing the reflectivity at different frequencies. Then, varying the orientation of the elliptical aperture from 0° to 180°, the reflected wave can generate a continuous 2 π range phase shift while keeping its amplitude high, which is necessary to achieve focusing. The metalens exhibits extraordinary tunability of focal length via uniformly changing the Fermi energy of graphene. The focus can be shifted above 72 µm with focusing efficiency reaching over 70%. In addition, the tunable metalens is also capable of broadband focusing modulation and plane focusing. The presented metalens exhibits outstanding focusing efficiency in dynamic focusing, thereby manifesting great practicability in dynamic imaging and robust stable imaging.

For patients with extensive skin defects, loss of sweat glands (SwGs) greatly decreases their quality of life. Indeed, difficulties in thermoregulation, ion reabsorption, and maintaining fluid balance might render them susceptible to hyperthermia, heatstroke, or even death. Despite extensive studies on the stem cell biology of the skin in recent years, in-situ regeneration of SwGs with both structural and functional fidelity is still challenging because of the limited regenerative capacity and cell fate control of resident progenitors. To overcome these challenges, one must consider both the intrinsic factors relevant to genetic and epigenetic regulation and cues from the cellular microenvironment. Here, we describe recent progress in molecular biology, developmental pathways, and cellular evolution associated with SwGdevelopment and maturation. This is followed by a summary of the current strategies used for cell-fate modulation, transmembrane drug delivery, and scaffold design associated with SwGregeneration. Finally, we offer perspectives for creating more sophisticated systems to accelerate patients' innate healing capacity and developing engineered skin constructs to treat or replace damaged tissues structurally and functionally.

Mesenchymal stem cells (MSCs) play an important role in cutaneous wound healing; however, the functional mechanisms involved in the healing process are poorly understood. A series of studies indicate that keratinocytes that migrate into the wound bed rely on an epithelial-mesenchymal transition (EMT)-like process to initiate re-epithelialization. We therefore examined whether bone marrow-derived MSCs (BMSCs) could affect biological behavior and induce EMT-like characteristics in the human epidermal keratinocytes (HEKs) and in the immortalized human keratinocyte cell line HaCaT cells, and we investigated the signaling pathways of BMSC-mediated phenotypic changes. By assessing the expression of EMT-related markers including E-cadherin, α-SMA, and Snail family transcription factors by β2-adrenergic receptor (β2-AR) blockage using ICI-118,551, a β2-AR selective antagonist, or β2-AR small interfering RNA (siRNA), we showed an involvement of β2-AR signaling in the induction of EMT-like alterations in human keratinocytes in vitro. β2-AR signaling also affected collective and individual cell migration in human keratinocyte cell lines, which was attenuated by administration of ICI-118,551. Treating the cells with BMSC-conditioned media (BMSC-CM) not only recapitulated the effect of isoproterenol (ISO) on cell migration but also induced the expression of β2-AR and a panel of proteins associated with mesenchymal phenotype in HEKs and HaCaT cells. Similarly, a blockade of the β2-AR by either ICI-118,551 or β2-AR siRNAs reversed both responses of the epidermal keratinocyte cell lines relative to BMSC-CM exposure. These results were further verified in our vivo findings and indicated that the exogenous application of MSCs promoted cutaneous wound healing and endowed the keratinocytes surrounding the wound area with an increased migratory phenotype through activation of β2-AR signaling. Our findings suggest a biochemical mechanism underlying the function of MSCs in wound re-epithelization, which provides a reliable theoretical basis for the wide application of MSCs in the treatment of chronic wounds.

In this paper, a method based on a backpropagation neural network (BPNN) is proposed to calculate the exposure buildup factor ( B D ) of a point isotropic source in an infinite homogeneous medium under arbitrary energy and mean free path (mfp). The results obtained for aluminum, iron, lead, and concrete based on BPNN are compared to ANSI/ANS-6.4.3 standard data, the results calculated by MCNP 5 Monte Carlo code, and a geometric progression (G-P) fitting formula, and show that the B D calculated by the BPNN model is more consistent with the ANS standard data. This method improves the calculation and fitting effect of B D compared to other methods. This paper proposes a systematic process combining a Monte Carlo method and BPNN to calculate and predict the B D of new materials under different energy and mfp, thus replacing the G-P fitting formula and improving calculation accuracy.

Mesenchymal stem cells (MSCs) play an important role in cutaneous wound healing; however, the functional mechanisms involved in the healing process are poorly understood. A series of studies indicate that keratinocytes that migrate into the wound bed rely on an epithelial-mesenchymal transition (EMT)-like process to initiate re-epithelialization. We therefore examined whether bone marrow-derived MSCs (BMSCs) could affect biological behavior and induce EMT-like characteristics in the human epidermal keratinocytes (HEKs) and in the immortalized human keratinocyte cell line HaCaT cells, and we investigated the signaling pathways of BMSC-mediated phenotypic changes. By assessing the expression of EMT-related markers including E-cadherin, α-SMA, and Snail family transcription factors by β