The role of KLRG1: a novel biomarker and new therapeutic target.

Killer cell lectin-like receptor G1 (KLRG1) is an immune checkpoint receptor expressed predominantly in NK and T-cell subsets that downregulates the activation and proliferation of immune cells and participates in cell-mediated immune responses. Accumulating evidence has demonstrated the importance of KLRG1 as a noteworthy disease marker and therapeutic target that can influence disease onset, progression, and prognosis. Blocking KLRG1 has been shown to effectively mitigate the effects of downregulation in various mouse tumor models, including solid tumors and hematologic malignancies. However, KLRG1 inhibitors have not yet been approved for human use, and the understanding of KLRG1 expression and its mechanism of action in various diseases remains incomplete. In this review, we explore alterations in the distribution, structure, and signaling pathways of KLRG1 in immune cells and summarize its expression patterns and roles in the development and progression of autoimmune diseases, infectious diseases, and cancers. Additionally, we discuss the potential applications of KLRG1 as a tool for tumor immunotherapy.

Ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis: a case report.

BACKGROUND: The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of co-occurring T-cell lymphocytosis and osseous metastasis being exceedingly rare. CASE PRESENTATION: A 51-year-old woman was admitted to our hospital with dyspnea and chest pain. Upon imaging examination, she was found to have diffuse and nodular pleural thickening on the left side, collapse of the left lung and a compression in the second thoracic vertebrae. All lesions showed significant 18F-FDG uptake on 18F-FDG PET/CT examination. Furthermore, she exhibited T-cell lymphocytosis in her peripheral blood, lymph nodes, and bone marrow. After ruling out malignant pleural mesothelioma (MPM), lung cancer with pleural metastasis, and T-cell lymphoma, the definitive diagnosis asserted was ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis. CONCLUSION: Physicians need to expand their knowledge of the imaging features of ectopic pleural thymoma. Cases with T-cell lymphocytosis may exhibit increased aggressiveness and prone to bone metastasis.

Antibody responses to SARS-CoV-2 Omicron infection in patients with hematological malignancies: A multicenter, prospective cohort study.

Little is known about antibody responses to natural Omicron infection and the risk factors for poor responders in patients with hematological malignancies (HM). We conducted a multicenter, prospective cohort study during the latest Omicron wave in Chongqing, China, aiming to compare the antibody responses, as assessed by IgG levels of anti-receptor binding domain of spike protein (anti-S-RBD), to Omicron infection in the HM cohort (HMC) with healthy control cohort (HCC), and solid cancer cohort (SCC). In addition, we intend to explore the risk factors for poor responders in the HMC. Among the 466 HM patients in this cohort, the seroconversion rate was 92.7%, no statistically difference compared with HCC (98.2%, p = 0.0513) or SCC (100%, p = 0.1363). The median anti-S-RBD IgG titer was 29.9 ng/mL, significantly lower than that of HCC (46.9 ng/mL, p < 0.0001) or SCC (46.2 ng/mL, p < 0.0001). Risk factors associated with nonseroconversion included no COVID-19 vaccination history (odds ratio [OR] = 4.58, 95% confidence interval [CI]: 1.75-12.00, p = 0.002), clinical course of COVID-19 ≤ 7 days (OR = 2.86, 95% CI: 1.31-6.25, p = 0.008) and severe B-cell reduction (0-10/µL) (OR = 3.22, 95% CI: 1.32-7.88, p = 0.010). Risk factors associated with low anti-S-RBD IgG titer were clinical course of COVID-19 ≤ 7 days (OR = 2.58, 95% CI: 1.59-4.18, p < 0.001) and severe B-cell reduction (0-10/µL) (OR = 2.87, 95% CI: 1.57-5.24, p < 0.001). This study reveals a poor antibody responses to Omicron (BA.5.2.48) infection in HM patients and identified risk factors for poor responders. Highlights that HM patients, especially those with these risk factors, may be susceptible to SARS-CoV-2 reinfection, and the postinfection vaccination strategies for these patients should be tailored. Clinical trial: ChiCTR2300071830.

Development and validation of nomogram prognostic model for predicting OS in patients with diffuse large B-cell lymphoma: a cohort study in China.

This study comprehensively incorporates pathological parameters and novel clinical prognostic factors from the international prognostic index (IPI) to develop a nomogram prognostic model for overall survival in patients with diffuse large B-cell lymphoma (DLBCL). The aim is to facilitate personalized treatment and management strategies. This study enrolled a total of 783 cases for analysis. LASSO regression and stepwise multivariate COX regression were employed to identify significant variables and build a nomogram model. The calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) curve were utilized to assess the model's performance and effectiveness. Additionally, the time-dependent concordance index (C-index) and time-dependent area under the ROC curve (AUC) were computed to validate the model's stability across different time points. The study utilized 8 selected clinical features as predictors to develop a nomogram model for predicting the overall survival of DLBCL patients. The model exhibited robust generalization ability with an AUC exceeding 0.7 at 1, 3, and 5 years. The calibration curve displayed evenly distributed points on both sides of the diagonal, and the slopes of the three calibration curves were close to 1 and statistically significant, indicating high prediction accuracy of the model. Furthermore, the model demonstrated valuable clinical significance and holds the potential for widespread adoption in clinical practice. The novel prognostic model developed for DLBCL patients incorporates readily accessible clinical parameters, resulting in significantly enhanced prediction accuracy and performance. Moreover, the study's use of a continuous general cohort, as opposed to clinical trials, makes it more representative of the broader lymphoma patient population, thus increasing its applicability in routine clinical care.

Cytoplasmic Expression of TP53INP2 Modulated by Demethylase FTO and Mutant NPM1 Promotes Autophagy in Leukemia Cells.

Acute myeloid leukemia (AML) with a nucleophosmin 1 (NPM1) mutation is a unique subtype of adult leukemia. Recent studies show that NPM1-mutated AML has high autophagy activity. However, the mechanism for upholding the high autophagic level is still not fully elucidated. In this study, we first identified that tumor protein p53 inducible nuclear protein 2 (TP53INP2) was highly expressed and cytoplasmically localized in NPM1-mutated AML cells. Subsequent data showed that the expression of TP53INP2 was upregulated by fat mass and obesity-associated protein (FTO)-mediated m6A modification. Meanwhile, TP53INP2 was delocalized to the cytoplasm by interacting with NPM1 mutants. Functionally, cytoplasmic TP53INP2 enhanced autophagy activity by promoting the interaction of microtubule-associated protein 1 light chain 3 (LC3) - autophagy-related 7 (ATG7) and further facilitated the survival of leukemia cells. Taken together, our study indicates that TP53INP2 plays an oncogenic role in maintaining the high autophagy activity of NPM1-mutated AML and provides further insight into autophagy-targeted therapy of this leukemia subtype.

Clinical characteristics and outcomes of newly diagnosed patients with HIV-associated aggressive B-cell NHL in China.

Little is known about the incidence, clinical characteristics and prognostic factors in HIV associated lymphoma as these are less common than HIV-negative lymphoma in China. Currently, there are no standard guidelines for treatment of these patients. Therefore, we performed a study to analyse the clinical characteristics and outcomes of newly diagnosed HIV-associated aggressive B-cell non-Hodgkin's lymphoma (NHL) patients in Chongqing University Cancer Hospital (CUCH). Totally 86 newly diagnosed HIV-associated aggressive B-cell NHL patients in CUCH, southwest China, from July 2008 to August 2021, were analysed. In the entire cohort, median age was 48 years (range, 23-87 years), and more patients were male (87.2%). Most patients had elevated lactate dehydrogenase (LDH) (82.6%), advanced ann arbor stage (80.2%) and high IPI score (IPI score, 3-5) (62.7%) at diagnosis. Median CD4+ T-cell count at diagnosis was 191/µl (range, 4-1022), 84 patients (97.7%) were on combination antiretroviral therapy (cART) at lymphoma diagnosis. In DLBCL patients, cox multivariate analysis showed that age ≥ 60 (HR = 2.251, 95%CI 1.122-4.516; p = 0.012), elevated LDH (HR = 4.452, 95%CI 1.027-19.297; p = 0.041) and received less than two cycles of chemotherapy (HR = 0.629, 95%CI 0.589-1.071; p = 0.012) were independent risk factors for adverse prognosis based on PFS. Age ≥ 60 (HR = 3.162, 95%CI 1.500-6.665; p = 0.002) and received less than two cycles of chemotherapy (HR = 0.524, 95%CI 0.347-0.791; p = 0.002) were also independent risk factor for adverse prognosis based on OS. In BL patients, cox multivariate analysis showed that elevated LDH and received less than two cycles of chemotherapy were independent risk factors for adverse prognosis. In the DLBCL group, median PFS times in the received rituximab and no received rituximab groups were not reached and 12 months, respectively (p = 0.006). Median OS times were not reached and 36 months, respectively (p = 0.021). In the BL group, median PFS times in the received rituximab and no received rituximab groups were not reached and 4.8 months, respectively (p = 0.046). Median OS times were not reached and 10.1 months, respectively (p = 0.035). Overall, these data indicated that standardized anti-lymphoma therapy and rituximab administration were significantly associated with improved outcomes in patients with HIV-associated DLBCL and BL.

NPM1 mutant maintains ULK1 protein stability via TRAF6-dependent ubiquitination to promote autophagic cell survival in leukemia.

Nucleophosmin (NPM1) mutations are the most frequent genetic alteration in acute myeloid leukemia (AML) and aberrant cytoplasm-dislocated NPM1 mutant is a distinct biological characterization of this disease. Our group previously reported that NPM1 mutant elevated autophagy activity and autophagy activation contributed to leukemic cell survival. However, the molecular mechanisms by which cytoplasmic NPM1 mutant involving in the autophagy pathway has not been fully elucidated. Here, we showed that Unc-51-like kinase 1 (ULK1) as a core autophagy protein was highly expressed in NPM1-mA positive OCI-AML3 cells and primary NPM1-mutated AML blasts. Meanwhile, we found that NPM1-mA could interact with ULK1 protein and positively regulated ULK1 protein levels. Mechanically, NPM1-mA promoted TRAF6-dependent K63 ubiquitination and further maintained ULK1 stability and kinase activity via miR-146a. In addition, ULK1 high expression-mediated autophagy activation and facilitated to leukemic cell proliferation. Finally, we demonstrated that restoring ULK1 expression, ULK1 inhibitor SBI-0206965 treatment and using shULK1 partially rescued the effect of NPM1-mA on autophagy and cell survival. In conclusion, our findings suggest that NPM1 mutant interacts with ULK1, and thus, maintains its protein stability, which is required for NPM1 mutant-mediated autophagic cell survival. These data extend our understanding of the functions of NPM1 mutant in the regulation of autophagy activation in NPM1-mutated AML.

Application of Multi-Electrode Resistivity Method on Semi-Diagenesis Rocks in Freezing Area and Its' Implications.

Recently, with the development of geophysical exploration technology, geophysical engineering instruments and methods have also improved. The multi-electrode resistivity method is widely used in engineering exploration. In this paper, multi-electrode resistivity tests were carried out in a seasonal frozen soil area in Heilongjiang Province, to provide an optimized multi-electrode resistivity method under the conditions of frozen soil. Combined with shear wave velocity tests and standard penetration tests, multi-electrode resistivity tests were used to comprehensively analyze and evaluate the physical and mechanical properties of Tertiary semi-diagenesis rocks. The results show that the high resistivity due to the frozen surface layer acting as a shield can be eliminated by technical means. It is feasible to test the resistivity through the frozen surface layer. The multi-electrode resistivity method can visually reflect the interface between saturated sand and semi-diagenetic rocks. Dividing the interface between saturated sand and semi-diagenetic rocks is advantageous as the morphology of the resistivity curve has a significant curvature change. There is a strong correlation between the resistance and shear wave velocity of a strata in which the Pearson correlation coefficient is as high as 0.99. The multi-electrode resistivity method test used in combination with the shear wave velocity test and the standard penetration test could give the bearing capacity and frictional resistance of semi-diagenetic rocks, which saves a lot of time and material costs in engineering exploration.

Multifunctional Theranostic Nanoplatform Based on Fe-mTa2O5@CuS-ZnPc/PCM for Bimodal Imaging and Synergistically Enhanced Phototherapy.

Multifunctional nanotheranostic agent with high performance for tumor site-specific generation of singlet oxygen (1O2) as well as imaging-guidance is crucial to laser-mediated photodynamic therapy. Here, we introduced a versatile strategy to design a smart nanoplatform using phase change material (PCM) to encapsulate photosensitizer (zinc phthalocyanine, ZnPc) in copper sulfide loaded Fe-doped tantalum oxide (Fe-mTa2O5@CuS) nanoparticles. When irradiated by 808 nm laser, the PCM is melted due to the hyperthermia effect from CuS nanoparticles, inducing the release of ZnPc to produce toxic 1O2 triggered by 650 nm light with very low power density (5 mW/cm2). Then, the produced heat and toxic 1O2 can kill tumor cells in vitro and in vivo effectively. Furthermore, the special properties of Fe-mTa2O5 endow the nanoplatform with excellent computed tomography (CT) and T1-weighted magnetic resonance imaging ( T1-MRI) performance for guiding and real-time monitoring of therapeutic effect. This work presents a feasible way to design smart nanoplatform for controllable generation of heat and 1O2, achieving CT/ T1-MRI dual-modal imaging-guided phototherapy.

Quantitative detection of circulating nucleophosmin mutations DNA in the plasma of patients with acute myeloid leukemia.

OBJECTIVE: The aim of this study was to quantify the copies of circulating nucleophosmin (NPM) mutations DNA in the plasma of patients with acute myeloid leukemia (AML) and to explore the association of circulating NPM mutation levels with clinical characteristics. DESIGN AND METHODS: The presence of NPM mutations in 100 Chinese patients newly diagnosed with AML were identified by RT-PCR and sequencing analysis. Copies of circulating NPM mutation A (NPM mut.A) DNA in the plasma of mutation-positive cases were quantified by real-time quantitative PCR (qRT-PCR). Furthermore, the association of circulating NPM mutation levels and clinical characteristics was analyzed. RESULTS: NPM mutations were identified in 37 of the 100 patients and all cases were NPM mut.A. The circulating NPM mut.A levels ranged from 0.35×10(8) copies/ml to 6.0×10(8) copies/ml in the 37 mutation-positive cases. The medium and quartile M (P25, P75) of the circulating NPM mut.A levels in patients classified as M2, M4 and M5 morphological subtypes were 1.35×10(8) (0.76×10(8), 1.91×10(8)) copies/ml, 1.81×10(8) (1.47×10(8), 2.2×10(8)) copies/ml and 2.50×10(8) (2.42×10(8), 3.05×10(8)) copies/ml, respectively. Circulating NPM mut.A levels were significantly higher in patients with the M5 subtype of AML compared to patients with the M2 and M4 subtypes (p=0.000, p=0.046). In addition, circulating NPM mut.A copies were significantly associated with a higher white blood cell count, platelet count and bone marrow blast percentage (p<0.05). CONCLUSION: Our results suggest that circulating NPM mutations DNA assay serves as a complementary to the routine investigative protocol of NPM-mutated leukemia.

A novel signature incorporating genes related to lipid metabolism and immune for prognostic and functional prediction of breast cancer.

PURPOSE: Breast cancer prognosis and functioning have not been thoroughly examined in relation to immunological and lipid metabolism. However, there is a lack of prognostic and functional analyses of the relationship between lipid metabolism and immunity in breast cancer. METHODS: DEGs in breast cancer were obtained from UCSC database, and lipid metabolism and immune-related genes were obtained from GSEA and Immune databases. A predictive signature was constructed using univariate Cox and LASSO regression on lipid metabolism and immune-related DEGs. The signature's prognostic significance was assessed using Kaplan-Meier, time-dependent ROC, and risk factor survival scores. Survival prognosis, therapeutic relevance, and functional enrichment were used to mine model gene biology. We selected IL18, which has never been reported in breast cancer before, in the signature to learn more about its function, potential to predict outcome, and immune system role. RT-PCR was performed to verify the true expression level of IL18. RESULTS: A total of 136 DEGs associated with breast cancer responses to both immunity and lipid metabolism. Nine key genes (CALR, CCL5, CEPT, FTT3, CXCL13, FLT3, IL12B, IL18, and IL24, p < 1.6e-2) of breast cancer were identified, and a prognostic was successfully constructed with a good predictive ability. IL18 in the model also had good clinical prognostic guidance value and immune regulation and therapeutic potential. Furthermore, the expression of IL18 was higher than that in paracancerous tissue. CONCLUSIONS: A unique predictive signature model could effectively predict the prognosis of breast cancer, which can not only achieve survival prediction, but also screen out key genes with important functional mechanisms to guide clinical drug experiments.

Cytoplasmic TP53INP2 acts as an apoptosis partner in TRAIL treatment: the synergistic effect of TRAIL with venetoclax in TP53INP2-positive acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor outcomes, especially in older AML patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered a promising anticancer drug because it selectively induces the extrinsic apoptosis of tumor cells without affecting normal cells. However, clinical trials have shown that the responses of patients to TRAIL are significantly heterogeneous. It is necessary to explore predictable biomarkers for the preselection of AML patients with better responsiveness to TRAIL. Here, we investigated the critical role of tumor protein p53 inducible nuclear protein 2 (TP53INP2) in the AML cell response to TRAIL treatment. METHODS: First, the relationship between TP53INP2 and the sensitivity of AML cells to TRAIL was determined by bioinformatics analysis of Cancer Cell Line Encyclopedia datasets, Cell Counting Kit-8 assays, flow cytometry (FCM) and cell line-derived xenograft (CDX) mouse models. Second, the mechanisms by which TP53INP2 participates in the response to TRAIL were analyzed by Western blot, ubiquitination, coimmunoprecipitation and immunofluorescence assays. Finally, the effect of TRAIL alone or in combination with the BCL-2 inhibitor venetoclax (VEN) on cell survival was explored using colony formation and FCM assays, and the effect on leukemogenesis was further investigated in a patient-derived xenograft (PDX) mouse model. RESULTS: AML cells with high TP53INP2 expression were more sensitive to TRAIL in vitro and in vivo. Gain- and loss-of-function studies demonstrated that TP53INP2 significantly enhanced TRAIL-induced apoptosis, especially in AML cells with nucleophosmin 1 (NPM1) mutations. Mechanistically, cytoplasmic TP53INP2 maintained by mutant NPM1 functions as a scaffold bridging the ubiquitin ligase TRAF6 to caspase-8 (CASP 8), thereby promoting the ubiquitination and activation of the CASP 8 pathway. More importantly, simultaneously stimulating extrinsic and intrinsic apoptosis signaling pathways with TRAIL and VEN showed strong synergistic antileukemic activity in AML cells with high levels of TP53INP2. CONCLUSION: Our findings revealed that TP53INP2 is a predictor of responsiveness to TRAIL treatment and supported a potentially individualized therapeutic strategy for TP53INP2-positive AML patients.

Predictive model of the efficiency of hematopoietic stem cell collection in patients with multiple myeloma and lymphoma based on multiple peripheral blood markers.

INTRODUCTION: Autologous hematopoietic stem cell transplantation (ASCT) has gained extensive application in the treatment of lymphoma and multiple myeloma (MM). Plenty of studies demonstrate that peripheral blood indicators could be considered potential predictive biomarkers for hematopoietic stem cells (HSCs) collection efficiency, including white blood cell count (WBC), monocyte count (Mono), platelet count (PLT), hematocrit, and hemoglobin levels. Currently, clinically practical predictive models based on these peripheral detection indicators to quickly, conveniently, and accurately predict collection efficiency are lacking. METHODS: In total, 139 patients with MM and lymphoma undergoing mobilization and collection of ASCT were retrospectively studied. The study endpoint was successful collection of autologous HSCs. We analyzed the effects of clinical characteristics and peripheral blood markers on collection success, and screened variables to establish a prediction model. We determined the optimal cutoff value of peripheral blood markers for predicting successful stem cell collection and the clinical value of a multi-marker prediction approach. We also established a prediction model for collection efficacy. RESULTS: Univariate and multivariate logistic regression analyses showed that the mobilization regimen, Mono, PLT, mononuclear cell count (MNC), and peripheral blood CD34+ cell count (PB CD34+ counts) were significant predictors of successful collection of peripheral blood stem cells (PBSC). Two predictive models were constructed based on the results of multivariate logistic analyses. Model 1 included the mobilization regimen, Mono, PLT, and MNC, whereas Model 2 included the mobilization regimen, Mono, PLT, MNC, and PB CD34+ counts. Receiver operating characteristic (ROC) curve analysis showed that the PB CD34+ counts, Model 1, and Model 2 could predict successful HSCs collection, with cutoff values of 26.92 × 106/L, 0.548, and 0.355, respectively. Model 1 could predict successful HSCs collection with a sensitivity of 84.62%, specificity of 75.73%, and area under the curve (AUC) of 0.863. Model 2 could predict successful HSCs collection with a sensitivity of 83.52%, specificity of 94.17%, and AUC of 0.946; thus, it was superior to the PB CD34+ counts alone. CONCLUSION: Our findings suggest that the combination of the mobilization regimen, Mono, PLT, MNC, and PB CD34+ counts before collection has predictive value for the efficacy of autologous HSCs collection in patients with MM and lymphoma. Using models based on these predictive markers may help to avoid over-collection and improve patient outcomes.

Analytical Study of SH Wave Scattering by a Circular Pipeline in an Inhomogeneous Concrete with Density Variation.

In this paper, the shear horizontal (SH) wave scattering by a circular pipeline in an inhomogeneous concrete with density variation is studied. A model of inhomogeneous concrete with density variation in the form of a polynomial-exponential coupling function is established. By using the complex function method and conformal transformation, the incident and scattering wave field of SH wave in concrete are obtained, and the analytic expression of dynamic stress concentration factor (DSCF) around the circular pipeline is given. The results show that the inhomogeneous density parameters, the wave number of the incident wave and the angle of the incident wave in concrete are important factors affecting the distribution of dynamic stress around the circular pipe in concrete with inhomogeneous density. The research results can provide a theoretical reference and a basis for analyzing the influence of circular pipeline on elastic wave propagation in an inhomogeneous concrete with density variation.

Development and validation of a nomogram model for predicting the risk of venous thromboembolism in lymphoma patients undergoing chemotherapy: a prospective cohort study conducted in China.

BACKGROUND: The mechanism of Venous thromboembolism (VTE) is complicated and difficult to prevent due to factors such as bone marrow invasion, therapy, and immune-mediated effects. This study aims to establish a nomogram model for predicting the risk of thrombosis in lymphoma patients undergoing chemotherapy, which has been increasing over the past 30 years. METHODS: The data of lymphoma patients from the Affiliated Cancer Hospital of Chongqing University in China between 2018 and 2020 were analyzed. This included age, sex, body mass index, ECOG score, histological type, Ann Arbour Stage, white blood cells count, haemoglobin level, platelet count, D-dimer level, and chemotherapy cycle. Univariate and multivariate cox analysis was used to determine the risk factors for VTE. Characteristic variables were selected to construct a nomogram model which was then evaluated using ROC curve and calibration. RESULTS: Age, sex, PLT, D-dimer and chemotherapy cycle were considered as independent influencing factors of VTE. The mean (standard deviation) of the C index, AUC and Royston D statistics of 1000 cross-validations of the Nomogram model were 0.78 (0.01), 0.81 (0.01) and 1.61(0.07), respectively. It indicates a good calibration degree and applicability value as shown by the calibration curve. The DCA curve showed a rough threshold range of 0.05-0.60 with a good model. CONCLUSIONS: We have established and validated a nomogram model for predicting the risk of thrombosis in lymphoma patients. This model can assess the risk of thrombosis in each individual patient, enabling the identification of high-risk groups and targeted preventive treatment.

Mutation of FLNA attenuating the migration of abdominal muscles contributed to Melnick-Needles syndrome (MNS) in a family with recurrent miscarriage.

BACKGROUND: Filamin A, encoded by the X-linked gene FLNA, links the cell membrane with the cytoskeleton and acts as a regulator of the actin cytoskeleton. Mutations in FLNA cause a large spectrum of congenital malformations during embryonic development, including Melnick-Needles syndrome (MNS). However, reports of MNS, especially in males, are rare, and the pathogenesis molecular mechanisms are not well understood. METHODS: We found a family with two consecutive miscarriages of similar fetuses with multiple malformations. DNA was extracted from peripheral blood and tissues, and whole exome sequencing was performed for genetic analysis. Then, we created a C57BL/6 mouse with a point mutation by CRISPR/Cas-mediated genome engineering. The migration of primary abdominal muscle cell was detected by wound healing assay. RESULTS: The first fetus showed congenital hygroma colli and omphalocele identified by ultrasound at 12 wks; the second fetus showed hygroma colli and thoraco abdominoschisis at 12 wks, with a new hemizygous mutation c.4420G>A in exon 26 of the FLNA gene, which is predicted to cause an amino acid substitution (p.Asp1474Asn). The mother and grandmother were both present in the c.4420G>A heterozygous state, and the mother's healthy brother had wild-type FLNA. These FLNA-mutated mice exhibited a broader central gap between the rectus abdominis than the wild type (WT), similar to the midline structure dysplasia of the abdominal wall in the two fetuses. Wound healing assays showed the attenuated migration capacity of abdominal muscle cells in mice with mutated FLNA. Finally, we summarized the cases of MNS with FLNA mutation from the accessible published literature thus far. CONCLUSION: Our research revealed a mutation site of the FLNA for MNS and explored the mechanism of midline structure dysplasia in the abdominal wall of male patients, which could provide more evidence for the clinical diagnosis and genetic counseling of families with these disorders.

Ultra-weak photon emission as a potential tool for evaluating the therapeutic effect of traditional Chinese medicine in patients with type 2 diabetes.

Background: Traditional Chinese medicine (TCM) has been used to prevent and treat type 2 diabetes (T2DM) for thousands of years. The holistic view of TCM and the "multitarget" characteristics of Chinese medicine have unique advantages in the prevention and treatment of T2DM. TCM syndrome differentiation and treatment are effective for T2DM; however, currently, the therapeutic effect of TCM is generally evaluated by asking for patients' subjective feelings, or by checking the changes in relevant indicators. The main problems are that the patient's descriptions are unclear and subjective, and although the self-reported symptoms may have improved significantly, the relevant indicators are sometimes not obvious, which cannot truly reflect the therapeutic effect of TCM. Therefore, it is urgent to develop a novel, sensitive, and noninvasive method to quantitatively evaluate the therapeutic effect of TCM. Methods: In this study, ultra-weak photon emission (UPE) was measured at four sites of hands of T2DM patients with Qi-Yin deficiency before treatment and after 1 and 2 weeks of treatment with TCM. The UPE intensity and spectral distribution were calculated and analyzed using the results measured at these four sites. Spearman's correlation coefficient was used to quantify the correlation between the UPE parameters and the syndrome scores of TCM. Results: The UPE intensity of T2DM patients with Qi-Yin deficiency decreased gradually with the course of the treatment and was significantly lower than that before the treatment. The ratio of photon counts between the wavelength ranges of 495-550 nm and 550-610 nm after the treatment was higher than that before the treatment and negatively correlated with the corresponding syndrome scores so that the degree of symptoms improvement could be characterized by the ratio (495-550 nm/550-610 nm). Conclusions: The therapeutic effect of TCM in T2DM patients with Qi-Yin deficiency can be shown at the level of UPE. UPE is a potential and noninvasive tool for evaluating the therapeutic effect of TCM in patients with T2DM.

DNA-scaffolded multivalent vaccine against SARS-CoV-2.

Short peptides are poor immunogens. One way to increase their immune responses is by arraying immunogens in multivalency. Simple and efficient scaffolds for spatial controlling the inter-antigen distance and enhancing immune activation are required. Here, we report a molecular vaccine design principle that maximally drives potent SARS-CoV-2 RBD subunit vaccine on DNA duplex to induce robust and efficacious immune responses in vivo. We expect that the DNA-peptide epitope platform represents a facile and generalizable strategy to enhance the immune response. STATEMENT OF SIGNIFICANCE: DNA scaffolds offer a biocompatible and convenient platform for arraying immunogens in multivalency antigenic peptides, and spatially control the inter-antigen distance. This can effectively enhance immune response. Peptide (instead of entire protein) vaccines are highly attractive. However, short peptides are poor immunogens. Our DNA scaffolded multivalent peptide immunogen system induced robust and efficacious immune response in vivo as demonstrated by the antigenic peptide against SARS-CoV-2. The present strategy could be readily generalized and adapted to prepare multivalent vaccines against other viruses or disease. Particularly, the different antigens could be integrated into one single vaccine and lead to super-vaccines that can protect the host from multiple different viruses or multiple variants of the same virus.

Overall structural seismic damage rapid assessment method based on period and displacement response characteristics.

The seismic damage state of building structure can be rapidly evaluated by coupling effect of structural displacement response and periodic characteristics. Firstly, the fundamental period calculation formula that adapts to the deformation pattern and distribution mode of horizontal seismic action for reinforced concrete frame structure is derived. Secondly, the seismic damage assessment standard of building structure considering period variation is established. Then, the seismic damage assessment method of building structure is constructed. Finally, the seismic damage example is used to verify the established evaluation method. The results show that the established research method has high accuracy and good engineering practicability.