Tumor phylogeography reveals block-shaped spatial heterogeneity and the mode of evolution in Hepatocellular Carcinoma.

Solid tumors are complex ecosystems with heterogeneous 3D structures, but the spatial intra-tumor heterogeneity (sITH) at the macroscopic (i.e., whole tumor) level is under-explored. Using a phylogeographic approach, we sequence genomes and transcriptomes from 235 spatially informed sectors across 13 hepatocellular carcinomas (HCC), generating one of the largest datasets for studying sITH. We find that tumor heterogeneity in HCC segregates into spatially variegated blocks with large genotypic and phenotypic differences. By dissecting the transcriptomic heterogeneity, we discover that 30% of patients had a "spatially competing distribution" (SCD), where different spatial blocks have distinct transcriptomic subtypes co-existing within a tumor, capturing the critical transition period in disease progression. Interestingly, the tumor regions with more advanced transcriptomic subtypes (e.g., higher cell cycle) often take clonal dominance with a wider geographic range, rejecting neutral evolution for SCD patients. Extending the statistical tests for detecting natural selection to many non-SCD patients reveal varying levels of selective signal across different tumors, implying that many evolutionary forces including natural selection and geographic isolation can influence the overall pattern of sITH. Taken together, tumor phylogeography unravels a dynamic landscape of sITH, pinpointing important evolutionary and clinical consequences of spatial heterogeneity in cancer.

MicroRNA-200 Loaded Lipid Nanoparticles Promote Intestinal Epithelium Regeneration in Canonical MicroRNA-Deficient Mice.

Intestinal epithelium undergoes regeneration after injuries, and the disruption of this process can lead to inflammatory bowel disease and tumorigenesis. Intestinal stem cells (ISCs) residing in the crypts are crucial for maintaining the intestinal epithelium's homeostasis and promoting regeneration upon injury. However, the precise role of DGCR8, a critical component in microRNA (miRNA) biogenesis, in intestinal regeneration remains poorly understood. In this study, we provide compelling evidence demonstrating the indispensable role of epithelial miRNAs in the regeneration of the intestine in mice subjected to 5-FU or irradiation-induced injury. Through a comprehensive pooled screen of miRNA function in Dgcr8-deficient organoids, we observe that the loss of the miR-200 family leads to the hyperactivation of the p53 pathway, thereby reducing ISCs and impairing epithelial regeneration. Notably, downregulation of the miR-200 family and hyperactivation of the p53 pathway are verified in colonic tissues from patients with active ulcerative colitis (UC). Most importantly, the transient supply of miR-200 through the oral delivery of lipid nanoparticles (LNPs) carrying miR-200 restores ISCs and promotes intestinal regeneration in mice following acute injury. Our study implies the miR-200/p53 pathway as a promising therapeutic target for active UC patients with diminished levels of the miR-200 family. Furthermore, our findings suggest that the clinical application of LNP-miRNAs could enhance the efficacy, safety, and acceptability of existing therapeutic modalities for intestinal diseases.

Multimodal molecular landscape of response to Y90-resin microsphere radioembolization followed by nivolumab for advanced hepatocellular carcinoma.

BACKGROUND: Combination therapy with radioembolization (yttrium-90)-resin microspheres) followed by nivolumab has shown a promising response rate of 30.6% in a Phase II trial (CA209-678) for advanced hepatocellular carcinoma (HCC); however, the response mechanisms and relevant biomarkers remain unknown. METHODS: By collecting both pretreatment and on-treatment samples, we performed multimodal profiling of tissue and blood samples and investigated molecular changes associated with favorable responses in 33 patients from the trial. RESULTS: We found that higher tumor mutation burden, NCOR1 mutations and higher expression of interferon gamma pathways occurred more frequently in responders. Meanwhile, non-responders tended to be enriched for a novel Asian-specific transcriptomic subtype (Kaya_P2) with a high frequency of chromosome 16 deletions and upregulated cell cycle pathways. Strikingly, unlike other cancer types, we did not observe any association between T-cell populations and treatment response, but tumors from responders had a higher proportion of CXCL9+/CXCR3+ macrophages. Moreover, biomarkers discovered in previous immunotherapy trials were not predictive in the current cohort, suggesting a distinctive molecular landscape associated with differential responses to the combination therapy. CONCLUSIONS: This study unraveled extensive molecular changes underlying distinctive responses to the novel treatment and pinpointed new directions for harnessing combination therapy in patients with advanced HCC.

Selective binding of retrotransposons by ZFP352 facilitates the timely dissolution of totipotency network.

Acquisition of new stem cell fates relies on the dissolution of the prior regulatory network sustaining the existing cell fates. Currently, extensive insights have been revealed for the totipotency regulatory network around the zygotic genome activation (ZGA) period. However, how the dissolution of the totipotency network is triggered to ensure the timely embryonic development following ZGA is largely unknown. In this study, we identify the unexpected role of a highly expressed 2-cell (2C) embryo specific transcription factor, ZFP352, in facilitating the dissolution of the totipotency network. We find that ZFP352 has selective binding towards two different retrotransposon sub-families. ZFP352 coordinates with DUX to bind the 2C specific MT2_Mm sub-family. On the other hand, without DUX, ZFP352 switches affinity to bind extensively onto SINE_B1/Alu sub-family. This leads to the activation of later developmental programs like ubiquitination pathways, to facilitate the dissolution of the 2C state. Correspondingly, depleting ZFP352 in mouse embryos delays the 2C to morula transition process. Thus, through a shift of binding from MT2_Mm to SINE_B1/Alu, ZFP352 can trigger spontaneous dissolution of the totipotency network. Our study highlights the importance of different retrotransposons sub-families in facilitating the timely and programmed cell fates transition during early embryogenesis.

A decade of liver organoids: Advances in disease modeling.

Liver organoids are three-dimensional cellular tissue models in which cells interact to form unique structures in culture. During the past 10 years, liver organoids with various cellular compositions, structural features, and functional properties have been described. Methods to create these advanced human cell models range from simple tissue culture techniques to complex bioengineering approaches. Liver organoid culture platforms have been used in various research fields, from modeling liver diseases to regenerative therapy. This review discusses how liver organoids are used to model disease, including hereditary liver diseases, primary liver cancer, viral hepatitis, and nonalcoholic fatty liver disease. Specifically, we focus on studies that used either of two widely adopted approaches: differentiation from pluripotent stem cells or epithelial organoids cultured from patient tissues. These approaches have enabled the generation of advanced human liver models and, more importantly, the establishment of patient-tailored models for evaluating disease phenotypes and therapeutic responses at the individual level.

An Integrative Analysis of Nasopharyngeal Carcinoma Genomes Unraveled Unique Processes Driving a Viral-Positive Cancer.

As one of few viral-positive cancers, nasopharyngeal carcinoma (NPC) is extremely rare across the world but very frequent in several regions of the world, including Southern China (known as the Cantonese cancer). Even though several genomic studies have been conducted for NPC, their sample sizes are relatively small and systematic comparison with other cancer types has not been explored. In this study, we collected four-hundred-thirty-one samples from six previous studies and provided the first integrative analysis of NPC genomes. Combining several statistical methods for detecting driver genes, we identified 25 novel drivers for NPC, including ATG14 and NLRC5. Many of these novel drivers are enriched in several important pathways, such as autophagy and immunity. By comparing NPC with many other cancer types, we found NPC is a unique cancer type in which a high proportion of patients (45.2%) do not have any known driver mutations (termed as "missing driver events") but have a preponderance of deletion events, including chromosome 3p deletion. Through signature analysis, we identified many known and novel signatures, including single-base signatures (n = 12), double-base signatures (n = 1), indel signatures (n = 9) and copy number signatures (n = 8). Many of these new signatures are involved in DNA repair and have unknown etiology and genome instability, implying an unprecedented dynamic mutational process possibly driven by complex interactions between viral and host genomes. By combining clinical, molecular and intra-tumor heterogeneity features, we constructed the first integrative survival model for NPC, providing a strong basis for patient prognosis and stratification. Taken together, we have performed one of the first integrative analyses of NPC genomes and brought unique genomic insights into tumorigenesis of a viral-driven cancer.

Betulinic Acid Inhibits the Stemness of Gastric Cancer Cells by Regulating the GRP78-TGF-ß1 Signaling Pathway and Macrophage Polarization.

Cancer stemness is the process by which cancer cells acquire chemoresistance and self-renewal in the tumor microenvironment. Glucose-regulated protein 78 (GRP78) is a biomarker for gastric cancer and is involved in cancer stemness. By inducing cancer stemness in various types of cancer, the polarization of macrophages into tumor-associated macrophages (TAMs) controls tumor progression. Betulinic acid (BA) is a bioactive natural compound with anticancer properties. However, whether GRP78 regulates TAM-mediated cancer stemness in the tumor microenvironment and whether BA inhibits GRP78-mediated cancer stemness in gastric cancer remain unknown. In this study, we investigated the role of GRP78 in gastric cancer stemness in a tumor microenvironment regulated by BA. The results indicated that BA inhibited not only GRP78-mediated stemness-related protein expression and GRP78-TGF-ß-mediated macrophage polarization into TAMs, but also TAM-mediated cancer stemness. Therefore, BA is a promising candidate for clinical application in combination-chemotherapy targeting cancer stemness.

Evaluation of brainstem function using vestibular evoked myogenic potentials in patients with early-stage Parkinson′s disease / 中华神经科杂志

Objective:To investigate whether vestibular-evoked myogenic potentials (VEMP) can be used to assess brainstem and its supplementary diagnostic value in patients with early-stage Parkinson′s disease (PD).Methods:A total of 123 patients with early-stage PD (PD group) diagnosed in the Department of Neurology of the Second Affiliated Hospital of Soochow University from January 2019 to January 2022 were consecutively enrolled, and 122 healthy controls (healthy control group) were included. Cervical VEMP (cVEMP) and ocular VEMP (oVEMP) examinations were performed on all subjects. VEMP parameters between the 2 groups were compared, and receiver operating characteristic curve was used to evaluate the auxiliary diagnostic efficacy of VEMP for early-stage PD. Correlations between VEMP parameters and motor and non-motor symptoms such as autonomic dysfunction were analyzed in the PD group using Spearman correlation analysis.Results:Bilateral latencies of cVEMP [left P1 latency (Lp13): 19.0 (16.4, 20.9) ms vs 13.1(12.0, 14.2) ms, Z=-11.18, left N1 latency (Ln23): 27.4 (24.6, 29.9) ms vs 21.2 (19.8, 23.0) ms, Z=-10.14; right P1 latency (Rp13): 18.8 (16.2, 20.9) ms vs 13.0 (11.7, 14.1) ms, Z=-10.84, right N1 latency (Rn23): 27.7 (24.3, 29.7) ms vs 21.1 (19.6, 22.9) ms, Z=-10.50] and bilateral latencies of oVEMP [left N1 latency (Ln10): 12.7 (10.7, 14.4) ms vs 10.4 (9.7, 11.4) ms, Z=-8.02, left P1 latency (Lp15): 16.5 (15.1, 18.3) ms vs 14.5 (13.4, 15.3) ms, Z=-7.96; right N1 latency (Rn10): 12.8 (11.4, 14.0) ms vs 10.5 (9.7, 11.5) ms, Z=-8.85, right P1 latency (Rp15): 16.7 (15.3, 18.3) ms vs 14.4 (13.3, 15.1) ms, Z=-9.39] of the PD group significantly prolonged compared to the healthy control group (all P<0.001). Compared to the healthy control group, the area under the curve (AUC) values of Lp13, Ln23, Rp13 and Rn23 of cVEMP in the PD group were all greater than 0.7, and the AUC values of Lp13 and Rp13 in the PD group were greater than 0.9 (all P<0.001); the AUC values of Ln10, Lp15, Rn10, and Rp15 of oVEMP in the PD group were all greater than 0.7 (all P<0.001). The Rn10-p15 corrected amplitude in PD patients was positively correlated with levodopa equivalent dose ( r=0.21, P=0.020). The Rn10 in PD patients was positively correlated with the Non-Motor Symptoms Questionnaire scores ( r=0.21, P=0.023). The Lp13-n23 corrected amplitude was negatively correlated with the Scale for Outcomes in Parkinson′s Disease-Autonomic scores ( r=-0.20, P=0.023). There was no significant correlation between VEMP parameters and Unified Parkinson′s Disease Rating Scale part Ⅲ score ( P>0.05). Conclusion:VEMP, especially cVEMP, as a non-invasive neuroelectrophysiological index, is an objective marker for brainstem damage and could be used for screening early-stage PD patients.

Development of parenting behavior scale for caregivers of children aged 2 to 6 years and analysis for its reliability and validity / 中华预防医学杂志

To develop a caregiver parenting behavior scale for children aged 2 to 6 years, and to verify its reliability and validity. This study recruited 1 350 caregivers of children aged 2 to 6 years. The item discrimination analysis and exploratory factor analysis were used to analyze the structure, dimensions and items of the scale. Homogeneity reliability, split-half reliability and test-retest reliability were used to analyze the reliability of the scale. Content validity and construct validity were used to analyze the validity of the scale. The results showed that the final scale contained 7 dimensions and 45 items. Cronbach's α coefficient of the total scale was 0.945; the coefficient of split half was 0.899; the test-retest reliability analysis showed that the correlation coefficients between the two tests were 0.893 (total score), 0.854 (social), 0.832 (language), 0.871 (gross motor), 0.893 (fine motor), 0.862 (cognitive), 0.832 (self-care), and 0.872 (sensory). The content validity analysis was carried out by two rounds of expert argumentation using Delphi expert consultation method. The Kendall coefficient of the items score in two rounds of Delphi expert consultation was 0.813 (P<0.01). The structure validity analysis showed that there were significant correlations between each dimension and the total scale, also between each dimension of the scale, and the extracted average variance values of each dimension was greater than the correlation coefficients between this dimension and other dimensions. In conclusion, the reliability and validity of the scale are qualified. It can be used as a tool to evaluate and guide the parenting behavior of caregivers of children aged 2 to 6 years.

A decade of liver organoids: Advances in disease modeling

Liver organoids are three-dimensional cellular tissue models in which cells interact to form unique structures in culture. During the past 10 years, liver organoids with various cellular compositions, structural features, and functional properties have been described. Methods to create these advanced human cell models range from simple tissue culture techniques to complex bioengineering approaches. Liver organoid culture platforms have been used in various research fields, from modeling liver diseases to regenerative therapy. This review discusses how liver organoids are used to model disease, including hereditary liver diseases, primary liver cancer, viral hepatitis, and nonalcoholic fatty liver disease. Specifically, we focus on studies that used either of two widely adopted approaches: differentiation from pluripotent stem cells or epithelial organoids cultured from patient tissues. These approaches have enabled the generation of advanced human liver models and, more importantly, the establishment of patient-tailored models for evaluating disease phenotypes and therapeutic responses at the individual level.

Advancements in MAFLD Modeling with Human Cell and Organoid Models.

Metabolic (dysfunction) associated fatty liver disease (MAFLD) is one of the most prevalent liver diseases and has no approved therapeutics. The high failure rates witnessed in late-phase MAFLD drug trials reflect the complexity of the disease, and how the disease develops and progresses remains to be fully understood. In vitro, human disease models play a pivotal role in mechanistic studies to unravel novel disease drivers and in drug testing studies to evaluate human-specific responses. This review focuses on MAFLD disease modeling using human cell and organoid models. The spectrum of patient-derived primary cells and immortalized cell lines employed to model various liver parenchymal and non-parenchymal cell types essential for MAFLD development and progression is discussed. Diverse forms of cell culture platforms utilized to recapitulate tissue-level pathophysiology in different stages of the disease are also reviewed.

Krüppel-like factor 5 rewires NANOG regulatory network to activate human naive pluripotency specific LTR7Ys and promote naive pluripotency.

Endogenous retroviruses (ERVs) have been reported to participate in pre-implantation development of mammalian embryos. In early human embryogenesis, different ERV sub-families are activated in a highly stage-specific manner. How the specificity of ERV activation is achieved remains largely unknown. Here, we demonstrate the mechanism of how LTR7Ys, the human morula-blastocyst-specific HERVH long terminal repeats, are activated by the naive pluripotency transcription network. We find that KLF5 interacts with and rewires NANOG to bind and regulate LTR7Ys; in contrast, the primed-specific LTR7s are preferentially bound by NANOG in the absence of KLF5. The specific activation of LTR7Ys by KLF5 and NANOG in pluripotent stem cells contributes to human-specific naive pluripotency regulation. KLF5-LTR7Y axis also promotes the expression of trophectoderm genes and contributes to the expanded cell potential toward extra-embryonic lineage. Our study suggests that HERVs are activated by cell-state-specific transcription machinery and promote stage-specific transcription network and cell potency.

Genome instability is associated with ethnic differences between Asians and Europeans in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the deadliest cancer types with diverse etiological factors across the world. Although large scale genomic studies have been conducted in different countries, integrative analysis of HCC genomes and ethnic comparison across cohorts are lacking. Methods: We first integrated genomes of 1,349 HCC patients from five large cohorts across the world and applied multiple statistical methods in identifying driver genes. Subsequently, we systematically compared HCC genomes and transcriptomes between Asians and Europeans using the TCGA cohort. Results: We identified 29 novel candidate driver genes, many of which are infrequent tumor suppressors driving late-stage tumor progression. When we systematically compared ethnic differences in the genomic landscape between Asian and European HCCs using the TCGA cohort (n = 348), we found little differences in driver frequencies. Through multi-modal integrative analysis, we found higher genomic instability in Asians together with a collection of molecular events ranging from tumor mutation burden (TMB), copy number alterations as well as transcriptomic subtypes segregating distinctively between two ethnic backgrounds. Strikingly, we identified an Asian specific transcriptomic subtype with multiple ethnically enriched genomic alterations, in particular chromosome 16 deletion, leading to a clinically aggressive RNA subgroup unique to Asians. Integrating multi-modal information, we found that survival models predict patient prognosis much better in Asians than in Europeans, demonstrating a higher potential for precision medicine applications in Asia. Conclusion: For the first time, we have uncovered an unprecedented amount of genomic differences segregating distinctively across ethnicities in HCC and highlighted the importance of differential disease biology and management in HCC across ethnic backgrounds.

Effectiveness of quality of care for patients with type 2 diabetes in China: findings from the Shanghai Integration Model (SIM) / 医学前沿

This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai, China. A total of 173 235 patients with type 2 diabetes in 2017 were included in the analysis. Profiles of risk factors and intermediate outcomes were determined. The patients had a mean age of 66.43 ± 8.12 (standard deviation (SD)) years and a mean diabetes duration of 7.95 ± 5.53 (SD) years. The percentage of patients who achieved the target level for HbA1c (< 7.0%) was 48.6%. Patients who achieved the target levels for blood pressure (BP) < 130/80 mmHg and low-density lipoprotein-cholesterol (LDL-c) < 2.6 mmol/L reached 17.5% and 34.0%, respectively. A total of 3.8% achieved all three target levels, and the value increased to 6.8% with an adaptation of the BP target level (< 140/90 mmHg) for those over 65 years. Multivariable analysis identified the factors associated with a great likelihood of achieving all three target levels: male, young age, short diabetes duration, low body mass index, macrovascular complications, no microvascular complications, prescribed with lipid-lowering medication, and no prescription of antihypertensive medication. In conclusion, nearly 50% and one-third of the patients with diabetes met the target levels for HbA1c and LDL-c, respectively, with a low percentage achieving the BP target level. The percentage of patients who achieved all three target levels needs significant improvement.

PAM4 rolling-shutter demodulation using a pixel-per-symbol labeling neural network for optical camera communications.

The typical optical camera communication (OCC) modulation scheme is based on binary intensity modulation. To increase the transmission data rate, multi-level modulation format is highly desirable. In this work, we bring forward and demonstrate a rolling shutter 4-level pulse amplitude modulation (PAM4) demodulation scheme for OCC systems using pixel-per-symbol labeling neural network (PPSL-NN) for the first time up to the authors' knowledge. A bit-rate distance product of 28.8 kbit/s • m per color is achieved. The proposed scheme is to calculate and re-sample the pixel-per-symbol (PPS) to make sure the same number of pixels in each PAM4 symbol is corresponding to a label for the neural network. Experiment results reveal that the proposed scheme can efficiently demodulate high speed PAM4 signal in the rolling shutter OCC pattern.

Emerging liver organoid platforms and technologies.

Building human organs in a dish has been a long term goal of researchers in pursue of physiologically relevant models of human disease and for replacement of worn out and diseased organs. The liver has been an organ of interest for its central role in regulating body homeostasis as well as drug metabolism. An accurate liver replica should contain the multiple cell types found in the organ and these cells should be spatially organized to resemble tissue structures. More importantly, the in vitro model should recapitulate cellular and tissue level functions. Progress in cell culture techniques and bioengineering approaches have greatly accelerated the development of advance 3-dimensional (3D) cellular models commonly referred to as liver organoids. These 3D models described range from single to multiple cell type containing cultures with diverse applications from establishing patient-specific liver cells to modeling of chronic liver diseases and regenerative therapy. Each organoid platform is advantageous for specific applications and presents its own limitations. This review aims to provide a comprehensive summary of major liver organoid platforms and technologies developed for diverse applications.

Photosensitized Electrospun Nanofibrous Filters for Capturing and Killing Airborne Coronaviruses under Visible Light Irradiation

To address the challenge of the airborne transmission of SARS-CoV-2, photosensitized electrospun nanofibrous membranes were fabricated to effectively capture and inactivate coronavirus aerosols. With an ultrafine fiber diameter ([~] 200 nm) and a small pore size ([~] 1.5 {micro}m), the optimized membranes caught 99.2% of the aerosols of the murine hepatitis virus A59 (MHV-A59), a coronavirus surrogate for SARS-CoV-2. In addition, rose bengal was used as the photosensitizer for the membranes because of its excellent reactivity in generating virucidal singlet oxygen, and the membranes rapidly inactivated 98.9% of MHV-A59 in virus-laden droplets only after 15 min irradiation of simulated reading light. Singlet oxygen damaged the virus genome and impaired virus binding to host cells, which elucidated the mechanism of disinfection at a molecular level. Membrane robustness was also evaluated, and no efficiency reduction for filtering MHV-A59 aerosols was observed after the membranes being exposed to both indoor light and sunlight for days. Nevertheless, sunlight exposure photobleached the membranes, reduced singlet oxygen production, and compromised the performance of disinfecting MHV-A59 in droplets. In contrast, the membranes after simulated indoor light exposure maintained their excellent disinfection performance. In summary, photosensitized electrospun nanofibrous membranes have been developed to capture and kill airborne environmental pathogens under ambient conditions, and they hold promise for broad applications as personal protective equipment and indoor air filters. SynopsisPhotosensitized electrospun nanofibrous filters with excellent capture-and-kill performance against coronaviruses were designed and implemented to prevent the airborne transmission of COVID-19. Table of Contents O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/454404v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@171d6corg.highwire.dtl.DTLVardef@18caad5org.highwire.dtl.DTLVardef@23b902org.highwire.dtl.DTLVardef@14746e4_HPS_FORMAT_FIGEXP M_FIG C_FIG

2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside-stimulated dental pulp stem cells-derived conditioned medium enhances cell activity and anti-inflammation.

BACKGROUND/PURPOSE: Dental pulp stem cells (DPSCs) contribute to the regeneration of various tissues and have superior proliferation, immune privilege, and anti-inflammation properties to other mesenchymal stem cells. 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (THSG) not only enhances the aforementioned properties of DPSCs but also promotes self-renewal and reprogramming-like ability. However, whether THSG enhances the aforementioned properties and abilities through direct or indirect interaction mechanisms remains unclear. To address this knowledge gap, we examined the effects of THSG-stimulated DPSC-derived conditioned medium (THSG-CM) on the activity and anti-inflammation properties of cells. MATERIALS AND METHODS: DPSCs were treated with various concentrations of THSG to produce THSG-CM, which was then collected, analyzed, and lyophilized. A cytokine profiling antibody assay was used to compare protein components between THSG-treated and nontreated CM. Human skin fibroblasts (HSFs) and human gingival fibroblasts (HGFs) were used to investigate the effect of THSG-CM on cell proliferation, anti-inflammation, and wound healing abilities; for this investigation, MTS assay, quantitative real-time PCR analysis, and 2-well silicone inserts wound model were conducted. RESULTS: We observed that THSG enhanced the secretion of growth- and immune-associated proteins in THSG-CM and increased the proliferation of HSFs and HGFs. Furthermore, THSG-CM significantly attenuated lipopolysaccharide-stimulated mRNA levels of cytokines in both cells and improved wound healing abilities. CONCLUSION: We conclude that THSG-CM had more beneficial effects on cell activity and anti-inflammation in the HSFs and HGFs than DPSC-derived CM. DPSC-derived CM can be developed into a cell-free regenerative strategy in the future, and its therapeutic efficacy may be improved by THSG-CM.

Development of Electrospun Nanofibrous Filters for Controlling Coronavirus Aerosols

Airborne transmission of SARS-CoV-2 plays a critical role in spreading COVID-19. To protect public health, we designed and fabricated electrospun nanofibrous air filters that hold promise for applications in personal protective equipment and indoor environment. Due to ultrafine nanofibers ([~]300 nm), the electrospun air filters had a much smaller pore size compared to the surgical mask and cloth masks (a couple of microns versus tens to hundreds of microns). A coronavirus strain was used to generate aerosols for filtration efficiency tests, which can better represent SARS-CoV-2 than other agents used for aerosol generation in previous studies. The electrospun air filters showed excellent performance by capturing up to 99.9% of coronavirus aerosols, which outperformed many commercial face masks. In addition, since NaCl aerosols have been widely used in filtration tests, we compared the filtration efficiency obtained from the coronavirus aerosols and the NaCl aerosols. The NaCl aerosols were demonstrated as an eligible surrogate for the coronavirus aerosols in the filtration tests, when air filters and face masks with diverse pore sizes, morphologies, and efficiencies were used. Our work paves a new avenue for advancing air filtration by developing electrospun nanofibrous air filters for controlling SARS-CoV-2 airborne transmission. Moreover, the removal efficiency of the NaCl aerosols can be reasonably translated into understanding how air filters capture the coronavirus aerosols. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=148 SRC="FIGDIR/small/20249046v1_ufig1.gif" ALT="Figure 1"> View larger version (59K): org.highwire.dtl.DTLVardef@1a40a5eorg.highwire.dtl.DTLVardef@a4af7forg.highwire.dtl.DTLVardef@1fdd2c5org.highwire.dtl.DTLVardef@118a34e_HPS_FORMAT_FIGEXP M_FIG Table of Contents C_FIG