ALKBH5 facilitates the progression of skin cutaneous melanoma via mediating ABCA1 demethylation and modulating autophagy in an m6A-dependent manner.

Background: N6-methyladenosine (m6A) is the most common and abundant mRNA modification, playing an essential role in biological processes and tumor development. However, the role of m6A methylation in skin cutaneous melanoma (SKCM) is not yet clear. This study analyzed the expression of m6A-related functional genes in SKCM and aimed to explore the key demethylase ALKBH5 mediated m6A modification and its potential mechanism in human SKCM. Methods: Based on public databases, the m6A-related gene expression landscape in SKCM was portrayed. MeRIP-Seq and RNA-Seq were used to recognize the downstream target of ALKBH5. In vivo and in vitro functional phenotype and rescue functional experiments were performed to explore the mechanism of the ALKBH5-m6A-ABCA1 axis in SKCM. Results: We found ALKBH5 upregulated in SKCM, associated with poor prognosis. ALKBH5 can promote melanoma cell proliferation, colony formation, migration, and invasion and inhibit autophagy in vitro, facilitating tumor growth and metastasis in vivo. We identified ABCA1, a membrane protein that assists cholesterol efflux, as a downstream target of ALKBH5-mediated m6A demethylation. Finally, our data demonstrated that ALKBH5 promoted SKCM via mediating ABCA1 downregulation by reducing ABCA1 mRNA stability in an m6A-dependent manner. Conclusion: Our findings exhibited the functional value of the key demethylase ALKBH5 mediated m6A modification in the progression of SKCM, suggesting the ALKBH5-m6A-ABCA1 axis as a potential therapeutic target in SKCM.

Asiaticoside Attenuates Blood-Spinal Cord Barrier Disruption by Inhibiting Endoplasmic Reticulum Stress in Pericytes After Spinal Cord Injury.

The blood-spinal cord barrier (BSCB) plays a vital role in the recovery of spinal cord function after spinal cord injury (SCI). Pericytes, pluripotent members of the neurovascular unit (NVU), receive signals from neighboring cells and are critical for maintaining CNS function. Therapeutic targets for the BSCB include endothelial cells (ECs) and glial cells, but few drugs target pericytes. This study was designed to explore whether asiaticoside has a positively effect on pericytes and the integrity of the BSCB. In this study, we found that asiaticoside could inhibit the loss of junction proteins just 1 day after SCI in vivo, but our in vitro study showed no significant differences in the expression of endothelial junction proteins between the control and asiaticoside treatment groups. We also found that asiaticoside could inhibit endoplasmic reticulum (ER) stress and pericyte apoptosis, which might be associated with the inhibition of junction protein reduction in ECs. Thus, we investigated the interactions between pericytes and ECs. Our results showed that asiaticoside could decrease the release of matrix metalloproteinase (MMP)-9 in pericytes and therefore upregulate the expression of junction proteins in ECs. Furthermore, the protective effect of asiaticoside on pericytes is related to the inhibition of ER stress via the MAPK signaling pathway. Taken together, our results demonstrate that asiaticoside treatment inhibits BSCB disruption and enhances functional recovery after SCI.

Novel approach for enhancing skin allograft survival by bioadhesive nanoparticles loaded with rapamycin.

Skin graft rejection is a significant challenge in skin allografts for skin defects, particularly in extensive burn injury patients when autografts are insufficient. Enhancing the survival duration of allogeneic skin grafts can improve the success rate of subsequent autologous skin grafting, thereby promoting the therapeutic efficacy for wound healing. Rapamycin (Rapa), a potent immunosuppressant with favorable efficacy in organ transplantation, is limited by its systemic administration-associated toxicity and side effects. Therefore, addressing the short survival time of allogeneic skin grafts and minimizing the toxicity related to systemic application of immunosuppressive agents is an urgent requirement. Here, we present a topical formulation based on bioadhesive poly (lactic acid)-hyperbranched polyglycerol nanoparticles (BNPs) with surface-modified encapsulation of Rapamycin (Rapa/BNPs), applied for local immunosuppression in a murine model of allogeneic skin grafts. Our Rapa/BNPs significantly prolong nanoparticle retention, reduce infiltration of T lymphocytes and macrophages, decrease the level of pro-inflammatory cytokines and ultimately extend skin allograft survival with little systemic toxicity compared to free Rapa or Rapamycin-loaded non-bioadhesive nanoparticles (Rapa/NNPs) administration. In conclusion, Rapa/BNPs effectively deliver local immunosuppression and demonstrate potential for enhancing skin allograft survival while minimizing localized inflammation, thus potentially increasing patient survival rates for various types of skin defects.

Verteporfin-Loaded Bioadhesive Nanoparticles for the Prevention of Hypertrophic Scar.

Hypertrophic scarring (HS) is a common skin injury complication with unmet needs. Verteporfin (VP) should be an ideal HS-targeted therapeutic drug due to its efficient fibrosis and angiogenesis inhibitory abilities. However, its application is restricted by its side effects such as dose-dependent cytotoxicity on normal cells. Herein, the bioadhesive nanoparticles encapsulated VP (VP/BNPs) are successfully developed to attenuate the side effects of VP and enhance its HS inhibition effects by limiting VP releasing slowly and stably in the lesion site but not diffusing easily to normal tissues. VP/BNPs displayed significant inhibition on the proliferation, migration, collagen deposition, and vessel formation of human hypertrophic scar fibroblasts (HSFBs) and dermal vascular endothelial cells (HDVECs). In a rat tail HS model, VP/BNPs treated HS exhibits dramatic scar repression with almost no side effects compared with free VP or VP-loaded non-bioadhesive nanoparticles (VP/NNPs) administration. Further immunofluorescence analysis on scar tissue serial sections validated VP/BNPs effectively inhibited the collagen deposition and angiogenesis by firmly confined in the scar tissue and persistently releasing VP targeted to nucleus Yes-associated protein (nYAP) of HSFBs and HDVECs. These findings collectively suggest that VP/BNPs can be a promising and technically advantageous agent for HS therapies.

Single-cell analysis reveals specific neuronal transition during mouse corticogenesis.

Background: Currently, the mechanism(s) underlying corticogenesis is still under characterization. Methods: We curated the most comprehensive single-cell RNA-seq (scRNA-seq) datasets from mouse and human fetal cortexes for data analysis and confirmed the findings with co-immunostaining experiments. Results: By analyzing the developmental trajectories with scRNA-seq datasets in mice, we identified a specific developmental sub-path contributed by a cell-population expressing both deep- and upper-layer neurons (DLNs and ULNs) specific markers, which occurred on E13.5 but was absent in adults. In this cell-population, the percentages of cells expressing DLN and ULN markers decreased and increased, respectively, during the development suggesting direct neuronal transition (namely D-T-U). Whilst genes significantly highly/uniquely expressed in D-T-U cell population were significantly enriched in PTN/MDK signaling pathways related to cell migration. Both findings were further confirmed by co-immunostaining with DLNs, ULNs and D-T-U specific markers across different timepoints. Furthermore, six genes (co-expressed with D-T-U specific markers in mice) showing a potential opposite temporal expression between human and mouse during fetal cortical development were associated with neuronal migration and cognitive functions. In adult prefrontal cortexes (PFC), D-T-U specific genes were expressed in neurons from different layers between humans and mice. Conclusion: Our study characterizes a specific cell population D-T-U showing direct DLNs to ULNs neuronal transition and migration during fetal cortical development in mice. It is potentially associated with the difference of cortical development in humans and mice.

Transmission-type photonic doping for high-efficiency epsilon-near-zero supercoupling.

Supercoupling effect is an exotic and counterintuitive physical phenomenon of epsilon-near-zero (ENZ) media, in which the light can be "squeezed" and tunneled through flexible channels substantially narrower than its wavelength. Theoretically, ENZ channels with infinitely small widths perform ideal supercoupling with full energy transmission and zero-phase advance. As a feasible solution to demonstrate ENZ supercoupling through a finite-width channel, photonic doping can assist the light in squeezing, but the resonant dopant introduces inevitable losses. Here, we propose an approach of transmission-type photonic doping to achieve proximate ideal ENZ supercoupling. In contrast to the conventional resonance-type photonic doping, our proposed transmission-type doping replaces high-quality-factor two-dimensional resonant doping modes with low-quality-factor one-dimensional modes, such that obviously high transmission efficiency and zero-phase advance in ENZ supercoupling is achieved and observed in experiments. Benefiting from the high-efficiency ENZ supercoupling, waveguides with near-total energy transmission can be engineered with arbitrary dimensions and shapes, serving as flexible power conduits in the paradigm of waveguide integrated circuits for future millimeter-wave and terahertz integrated circuit innovations.

Intestinal activating transcription factor 4 regulates stress-related behavioral alterations via paraventricular thalamus in male mice.

Chronic stress induces depression- and anxiety-related behaviors, which are common mental disorders accompanied not only by dysfunction of the brain but also of the intestine. Activating transcription factor 4 (ATF4) is a stress-induced gene, and we previously show that it is important for gut functions; however, the contribution of the intestinal ATF4 to stress-related behaviors is not known. Here, we show that chronic stress inhibits the expression of ATF4 in gut epithelial cells. ATF4 overexpression in the colon relieves stress-related behavioral alterations in male mice, as measured by open-field test, elevated plus-maze test, and tail suspension test, whereas intestine-specific ATF4 knockout induces stress-related behavioral alterations in male mice. Furthermore, glutamatergic neurons are inhibited in the paraventricular thalamus (PVT) of two strains of intestinal ATF4-deficient mice, and selective activation of these neurons alleviates stress-related behavioral alterations in intestinal ATF4-deficient mice. The highly expressed gut-secreted peptide trefoil factor 3 (TFF3) is chosen from RNA-Seq data from ATF4 deletion mice and demonstrated decreased in gut epithelial cells, which is directly regulated by ATF4. Injection of TFF3 reverses stress-related behaviors in ATF4 knockout mice, and the beneficial effects of TFF3 are blocked by inhibiting PVT glutamatergic neurons using DREADDs. In summary, this study demonstrates the function of ATF4 in the gut-brain regulation of stress-related behavioral alterations, via TFF3 modulating PVT neural activity. This research provides evidence of gut signals regulating stress-related behavioral alterations and identifies possible drug targets for the treatment of stress-related behavioral disorders.

Collagen scaffolds derived from bovine skin loaded with MSC optimized M1 macrophages remodeling and chronic diabetic wounds healing.

Owing to the persistent inflammatory microenvironment and unsubstantial dermal tissues, chronic diabetic wounds do not heal easily and their recurrence rate is high. Therefore, a dermal substitute that can induce rapid tissue regeneration and inhibit scar formation is urgently required to address this concern. In this study, we established biologically active dermal substitutes (BADS) by combining novel animal tissue-derived collagen dermal-replacement scaffolds (CDRS) and bone marrow mesenchymal stem cells (BMSCs) for the healing and recurrence treatments of chronic diabetic wounds. The collagen scaffolds derived from bovine skin (CBS) displayed good physicochemical properties and superior biocompatibility. CBS loaded with BMSCs (CBS-MCSs) could inhibit M1 macrophage polarization in vitro. Decreased MMP-9 and increased Col3 at the protein level were detected in CBS-MSCs-treated M1 macrophages, which may be attributed to the suppression of the TNF-α/NF-κB signaling pathway (downregulating phospho-IKKα/ß/total IKKα/ß, phospho-IκB/total IκB, and phospho-NFκB/total NFκB) in M1 macrophages. Moreover, CBS-MSCs could benefit the transformation of M1 (downregulating iNOS) to M2 (upregulating CD206) macrophages. Wound-healing evaluations demonstrated that CBS-MSCs regulated the polarization of macrophages and the balance of inflammatory factors (pro-inflammatory: IL-1ß, TNF-α, and MMP-9; anti-inflammatory: IL-10 and TGF-ß3) in db/db mice. Furthermore, CBS-MSCs facilitated the noncontractile and re-epithelialized processes, granulation tissue regeneration, and neovascularization of chronic diabetic wounds. Thus, CBS-MSCs have a potential value for clinical application in promoting the healing of chronic diabetic wounds and preventing the recurrence of ulcers.

Stiffness Restricts the Stemness of the Intestinal Stem Cells and Skews Their Differentiation Toward Goblet Cells.

BACKGROUND & AIMS: Fibrosis and tissue stiffening are hallmarks of inflammatory bowel disease (IBD). We have hypothesized that the increased stiffness directly contributes to the dysregulation of the epithelial cell homeostasis in IBD. Here, we aim to determine the impact of tissue stiffening on the fate and function of the intestinal stem cells (ISCs). METHODS: We developed a long-term culture system consisting of 2.5-dimensional intestinal organoids grown on a hydrogel matrix with tunable stiffness. Single-cell RNA sequencing provided stiffness-regulated transcriptional signatures of the ISCs and their differentiated progeny. YAP-knockout and YAP-overexpression mice were used to manipulate YAP expression. In addition, we analyzed colon samples from murine colitis models and human IBD samples to assess the impact of stiffness on ISCs in vivo. RESULTS: We demonstrated that increasing the stiffness potently reduced the population of LGR5+ ISCs and KI-67+-proliferating cells. Conversely, cells expressing the stem cell marker, olfactomedin-4, became dominant in the crypt-like compartments and pervaded the villus-like regions. Concomitantly, stiffening prompted the ISCs to preferentially differentiate toward goblet cells. Mechanistically, stiffening increased the expression of cytosolic YAP, driving the extension of olfactomedin-4+ cells into the villus-like regions, while it induced the nuclear translocation of YAP, leading to preferential differentiation of ISCs toward goblet cells. Furthermore, analysis of colon samples from murine colitis models and patients with IBD demonstrated cellular and molecular remodeling reminiscent of those observed in vitro. CONCLUSIONS: Collectively, our findings highlight that matrix stiffness potently regulates the stemness of ISCs and their differentiation trajectory, supporting the hypothesis that fibrosis-induced gut stiffening plays a direct role in epithelial remodeling in IBD.

Intestinal Epithelial Cell-specific Deletion of Cytokine-inducible SH2-containing Protein Alleviates Experimental Colitis in Ageing Mice.

BACKGROUND AND AIMS: The incidence of inflammatory bowel disease [IBD] in the elderly has increased in recent years. However, the mechanisms underlying the ageing-related IBD susceptibility remain elusive. Cytokine-inducible SH2-containing protein [CISH] is involved in regulating metabolism, the expansion of intestinal tuft cells and type-2 innate lymphoid cells, and ageing-related airway inflammation. Here, we investigated the role of CISH in ageing-related colitis susceptibility. METHODS: CISH and phosphorylated signal transducer and activator of transcription-3 [p-STAT3] levels were evaluated in the colons of ageing mice and older ulcerative colitis [UC] patients. Mice with intestinal epithelial cell-specific knockout of Cish [CishΔIEC] and Cish-floxed mice were administered dextran sodium sulphate [DSS] or trinitrobenzene sulphonic acid [TNBS] to induce colitis. Colonic tissues were analysed in quantitative real-time polymerase chain reaction, immunoblotting, immunohistochemical, and histological staining experiments. Differentially expressed genes from colonic epithelia were analysed by RNA sequencing. RESULTS: Ageing increased the severity of DSS-induced colitis and the expression of colonic epithelial CISH in mice. CishΔIEC prevented DSS- or TNBS-induced colitis in middle-aged mice but not in young mice. RNA-sequencing analysis revealed that CishΔIEC significantly suppressed DSS-induced oxidative stress and proinflammatory responses. During ageing in the CCD841 cell model, knockdown of CISH decreased ageing-induced oxidative stress and proinflammatory responses, whereas these effects were compromised by knocking down or inhibiting STAT3. The increase in CISH expression was higher in the colonic mucosa of older patients with UC than in that of healthy controls. CONCLUSIONS: CISH might be a proinflammatory regulator in ageing; therefore, targeted therapy against CISH may provide a novel strategy for treating ageing-related IBD.

Inhibition of c-Jun in AgRP neurons increases stress-induced anxiety and colitis susceptibility.

Psychiatric disorders, such as anxiety, are associated with inflammatory bowel disease (IBD), however, the neural mechanisms regulating this comorbidity are unknown. Here, we show that hypothalamic agouti-related protein (AgRP) neuronal activity is suppressed under chronic restraint stress (CRS), a condition known to increase anxiety and colitis susceptibility. Consistently, chemogenic activation or inhibition of AgRP neurons reverses or mimics CRS-induced increase of anxiety-like behaviors and colitis susceptibility, respectively. Furthermore, CRS inhibits AgRP neuronal activity by suppressing the expression of c-Jun. Moreover, overexpression of c-Jun in these neurons protects against the CRS-induced effects, and knockdown of c-Jun in AgRP neurons (c-Jun∆AgRP) promotes anxiety and colitis susceptibility. Finally, the levels of secreted protein thrombospondin 1 (THBS1) are negatively associated with increased anxiety and colitis, and supplementing recombinant THBS1 rescues colitis susceptibility in c-Jun∆AgRP mice. Taken together, these results reveal critical roles of hypothalamic AgRP neuron-derived c-Jun in orchestrating stress-induced anxiety and colitis susceptibility.

Integration of single-cell and bulk transcriptomics reveals immune-related signatures in keloid.

BACKGROUND: Keloid is a pathological dermatological condition that manifests as an overgrowth scar secondary to skin trauma. This study endeavored to excavate immune-related signatures of keloid based on single-cell RNA (scRNA) sequencing data and bulk RNA sequencing data. METHOD: The keloid-relevant scRNA sequencing dataset GSE163973 and bulk RNA sequencing dataset GSE113619 were mined from the GEO database. The "Seurat" R package was utilized for data quality control, cell clustering, and investigation of marker genes of each cell cluster. The "SingleR" package helped match the marker genes of the corresponding cluster to specific cell types. Moreover, the R package "Monocle" was deployed for pseudotemporal ordering analysis, and the "clusterProfiler" was applied for functional and pathway enrichment analysis. The immune-related signatures were then identified, and potential targeted drugs were predicted via the DGIdb database. Verification of the immune-related signatures in clinical validation samples was implemented by RT-qPCR. RESULTS: Totally 23 cell clusters were screened and classified into 10 cell types based on the scRNA sequencing data. The keloid group had a significantly higher endothelial cell proportion than the control group. As enrichment analysis was applied in both differentially expressed genes (DEGs) of scRNA and bulk RNA sequencing data, we found they were enriched in multiple common immune-related pathways and biological processes. Meanwhile, we acquired three immune-related signatures (VCAM1, CALCRL, and HLA-DPB1) by intersecting the above DEGs with immune-related genes (IRGs). Then, we predicted 16 drugs potentially targeting the biomarkers through the DGIdb database. Finally, the outcome of RT-qPCR of clinical validation samples further verified the results. CONCLUSION: In conclusion, we analyzed the cell types and functional differences in the keloid through scRNA and bulk RNA sequencing data. We identified three immune-related signatures (VCAM1, CALCRL, and HLA-DPB1) in keloid, providing a basis for further in-depth investigation of the molecular mechanisms of keloid and exploration of therapeutic targets.

Early detection of visual impairment in young children using a smartphone-based deep learning system.

Early detection of visual impairment is crucial but is frequently missed in young children, who are capable of only limited cooperation with standard vision tests. Although certain features of visually impaired children, such as facial appearance and ocular movements, can assist ophthalmic practice, applying these features to real-world screening remains challenging. Here, we present a mobile health (mHealth) system, the smartphone-based Apollo Infant Sight (AIS), which identifies visually impaired children with any of 16 ophthalmic disorders by recording and analyzing their gazing behaviors and facial features under visual stimuli. Videos from 3,652 children (≤48 months in age; 54.5% boys) were prospectively collected to develop and validate this system. For detecting visual impairment, AIS achieved an area under the receiver operating curve (AUC) of 0.940 in an internal validation set and an AUC of 0.843 in an external validation set collected in multiple ophthalmology clinics across China. In a further test of AIS for at-home implementation by untrained parents or caregivers using their smartphones, the system was able to adapt to different testing conditions and achieved an AUC of 0.859. This mHealth system has the potential to be used by healthcare professionals, parents and caregivers for identifying young children with visual impairment across a wide range of ophthalmic disorders.

Development of a high energy resolution and wide dose rate range portable gamma-ray spectrometer.

In this paper, a portable gamma-ray spectrometer for real-time and in-situ gamma-ray detection applications is presented. By combining a quasi-hemispherical CdZnTe (CZT) semiconductor detector and a Geiger-Muller (GM) counter together, a wide dose rate range is achieved, ranging from 0.1 µSv/h to 100 mSv/h with a relative error of less than 10%. The GM counter is used to measure dose rate from 1 mSv/h to 100 mSv/h. With CZT, the spectrometer can provide a high energy resolution spectrum for nuclide identification and a high precision dose rate at low dose rates. The full width half maximum (FWHM) resolution is 2.2% at 662 keV below 70 µSv/h and is better than 3.3% at 3.8 mSv/h. The weight of the spectrometer is 3.2 kg for handheld and the runtime is up to 12 h without charging. For preliminary applications, the spectrometer was used to measure the gamma radiation around the Back-n white neutron beam line at China Spallation Neutron Source and around the steam generator in the nuclear power plant at Daya Bay Nuclear Power Station.

TEDD: a database of temporal gene expression patterns during multiple developmental periods in human and model organisms.

Characterization of the specific expression and chromatin profiles of genes enables understanding how they contribute to tissue/organ development and the mechanisms leading to diseases. Whilst the number of single-cell sequencing studies is increasing dramatically; however, data mining and reanalysis remains challenging. Herein, we systematically curated the up-to-date and most comprehensive datasets of sequencing data originating from 2760 bulk samples and over 5.1 million single-cells from multiple developmental periods from humans and multiple model organisms. With unified and systematic analysis, we profiled the gene expression and chromatin accessibility among 481 cell-types, 79 tissue-types and 92 timepoints, and pinpointed cells with the co-expression of target genes. We also enabled the detection of gene(s) with a temporal and cell-type specific expression profile that is similar to or distinct from that of a target gene. Additionally, we illustrated the potential upstream and downstream gene-gene regulation interactions, particularly under the same biological process(es) or KEGG pathway(s). Thus, TEDD (Temporal Expression during Development Database), a value-added database with a user-friendly interface, not only enables researchers to identify cell-type/tissue-type specific and temporal gene expression and chromatin profiles but also facilitates the association of genes with undefined biological functions in development and diseases. The database URL is https://TEDD.obg.cuhk.edu.hk/.

Impedance matching via ultrathin metatronic layer assisted by Smith Chart.

Metatronics, as a feasible paradigm of nanocircuits using effective electronic elements (e.g., nanocapacitors, nanoinductors, and nanoresistors), provides the possibility for light manipulation in subwavelength scales assisted by the circuit-related technologies in electronics. As a representative technique in electronics, Smith Chart provides a fast, less-computation and graphical approach to solve the problems related to impedance matching. Here, we transplant the Smith Chart into the paradigm of optical metatronics to develop an analytical approach for impedance matching for light propagation and coined the name of graphical metatronics. In this approach, the impedance characteristics of four basic types of ultrathin metatronic layers are creatively mapped into each rotation trace on the complex Γ mathematical plane (Γ means the reflection coefficient). The impedance matching problems can be graphically solved by searching for feasible rotation traces on the Γ plane without full-wave simulations. Based on this approach, various applications related to impedance matching (e.g., antireflection coating, perfect transmission, absorber, etc.) are developed analytically and validated by numerical results. The proposed approach constructs the bridge among Smith Chart, plasmonics and photonics, providing a fast, visualized and less-computation route and guideline to develop various nanophotonic structures and devices for impedance-matching applications.

Histopathological findings of the nasopharynx-associated lymphoid tissue of pigs co-infected with porcine circovirus 2 and porcine reproductive and respiratory syndrome virus.

Porcine circovirus 2 (PCV2) causes porcine circovirus-associated disease, and co-infection with porcine reproductive and respiratory syndrome virus (PRRSV) severely affects the pig breeding industry. Both viruses target the macrophages in lymphoid tissues. Various porcine pathogens enter via the nasal cavity, and the nasopharynx-associated lymphoid tissue (NALT) acts as the mucosal immune system. However, the pathological analysis has not progressed. This study aimed to histologically examine the NALT of pigs with suspected PCV2 and PRRSV infections. Six pigs were subjected to necropsy, and their NALT, tonsils, and mesenteric lymph nodes were collected. Macrophages, lymphocytic depletion, multinucleated giant cells, intracytoplasmic inclusion bodies, and neutrophil infiltration increased in the NALT. In situ hybridization revealed positive signals for PCV2 in the NALT of all pigs and PRRSV in the NALT of three pigs. PCV2-positive macrophages were mainly identified in the follicles, whereas PRRSV-positive tissues were found primarily around the crypt and directly below the epithelium. Quantitative PCR revealed 108-1010 copies of PCV2 DNA/µL and 102-104 copies of PRRSV DNA/µL in the NALT. Therefore, both PCV2 and PRRSV were detected in the NALT of pigs. In conclusion, the infection and replication of both viruses in the NALT and tonsils may suppress host immunity and promote co-infection with other pathogens.

Factors influencing and long-term effects of manual myotomy phenomenon during physiotherapy for congenital muscular torticollis.

PURPOSE: To investigate the factors influencing and long-term effects of manual myotomy (MM) occurring during physiotherapy for congenital muscular torticollis (CMT). METHODS: We retrospectively collected the clinical data of children with CMT receiving physiotherapy between 2008 and 2018. The children were divided into manual myotomy (MM) and non-manual myotomy (NMM) groups according to whether MM occurred during treatment. We assessed physiotherapy outcomes in children with CMT using craniofacial asymmetry parameters and the Cheng-Tang rating score. By measuring the ear-eye distance, ear-nose distance, eye-mouth distance, ear-mouth distance, half-head circumference, and half-head top at two sides to evaluate craniofacial asymmetry. Based on the Cheng-Tang assessment criteria, we recorded the range of rotation, range of lateral flexion, the status of the contracted muscle, the hardness of the mass, the extent of head tilting during activities and sleeping, the status of daily activities, face size, type of head shape, cranial changes, and subjective head tilting to assess the effectiveness of treatment. Clinical data and outcome indicators (craniofacial asymmetry parameters and Cheng-Tang rating score) were compared. RESULTS: The MM group had a significantly higher total Cheng-Tang rating score than the NMM group (P < 0.05). Age at initial physiotherapy session was the risk factor for MM during physiotherapy. CONCLUSION: Children with CMT developing MM during physiotherapy generally have a good outcome, although we do not recommend MM as a goal of treatment. Physiotherapists should understand this phenomenon, assess relevant factors to predict risk, and carefully observe treatment to prevent possible complications.

"I'm walking on eggshells": challenges faced by mothers with breast cancer in interacting with adolescent daughters.

BACKGROUND: With breast cancer becoming the most diagnosed cancer in the world, the number of breast cancer-afflicted mothers with adolescent daughters is also rising. Further, adolescent daughters' mothers serve as role models for in identity formation processes, especially concerning gender and sexuality. Nevertheless, breast cancer threats mother's health, including such a key symbol of her womanhood-the breast-which may adversely affect the development of an adolescent daughter's own sense of personal identity and womanhood. However, few researchers and practitioners have paid attention to mother-daughter interactions in the context of breast cancer. Therefore, this study aimed to uncover the nuances of the interactive challenges with adolescent daughters from breast cancer-afflicted mothers' perspective. METHODS: We conducted a qualitative study following the sample saturation principle, collecting data through semi-structured interviews with 21 breast cancer patients who met the inclusion criteria. We utilized thematic analysis and partially integrated the Foucauldian discourse approach to analyze the data. RESULTS: Three major themes emerged from the data: (1) mothers are lost in chaos (inability to handle the shock of cancer, feelings of powerlessness about the uncertainty of their life span, and confusion about how to respond to daughter's curiosity); (2) mothers struggle to maintain balance (torn between protecting daughters and letting them be independent, and making a tough choice between being a mother or a patient); and (3) mothers are immersed in guilt (increasing daughters' risk of cancer, influencing daughters' development, and imposing burdens on daughters). CONCLUSIONS: Our research explored the interactive experience of breast cancer-afflicted mothers and adolescent daughters. The insights uncovered by this study will help mothers enhance interaction with their daughters and assist health practitioners in devising interventions.

Direct observation of ideal electromagnetic fluids.

Near-zero-index (NZI) media have been theoretically identified as media where electromagnetic radiations behave like ideal electromagnetic fluids. Within NZI media, the electromagnetic power flow obeys equations similar to those of motion for the velocity field in an ideal fluid, so that optical turbulence is intrinsically inhibited. Here, we experimentally observe the electromagnetic power flow distribution of such an ideal electromagnetic fluid propagating within a cutoff waveguide by a semi-analytical reconstruction technique. This technique provides direct proof of the inhibition of electromagnetic vorticity at the NZI frequency, even in the presence of complex obstacles and topological changes in the waveguide. Phase uniformity and spatially-static field distributions, essential characteristics of NZI materials, are also observed. Measurement of the same structure outside the NZI frequency range reveals existence of vortices in the power flow, as expected for conventional optical systems. Therefore, our results provide an important step forward in the development of ideal electromagnetic fluids, and introduce a tool to explore the subwavelength behavior of NZI media including fully vectorial and phase information.