Reconfigurable refraction manipulation at synthetic temporal interfaces with scalar and vector gauge potentials.

Photonic gauge potentials, including scalar and vector ones, play fundamental roles in emulating photonic topological effects and for enabling intriguing light transport dynamics. While previous studies mainly focus on manipulating light propagation in uniformly distributed gauge potentials, here we create a series of gauge-potential interfaces with different orientations in a nonuniform discrete-time quantum walk and demonstrate various reconfigurable temporal-refraction effects. We show that for a lattice-site interface with the potential step along the lattice direction, the scalar potentials can yield total internal reflection (TIR) or Klein tunneling, while vector potentials manifest direction-invariant refractions. We also reveal the existence of penetration depth for the temporal TIR by demonstrating frustrated TIR with a double lattice-site interface structure. By contrast, for an interface emerging in the time-evolution direction, the scalar potentials have no effect on the packet propagation, while the vector potentials can enable birefringence, through which we further create a "temporal superlens" to achieve time-reversal operations. Finally, we experimentally demonstrate electric and magnetic Aharonov-Bohm effects using combined lattice-site and evolution-step interfaces of either scalar or vector potential. Our work initiates the creation of artificial heterointerfaces in synthetic time dimension by employing nonuniformly and reconfigurable distributed gauge potentials. This paradigm may find applications in optical pulse reshaping, fiber-optic communications, and quantum simulations.

A Chimeric Classical Insect-Specific Flavivirus Provides Complete Protection Against West Nile Virus Lethal Challenge in Mice.

West Nile virus (WNV), an arthropod-borne flavivirus, can cause severe symptoms, including encephalitis, and death, posing a threat to public health and the economy. However, there is still no approved treatment or vaccine available for humans. Here, we developed a novel vaccine platform based on a classical insect-specific flavivirus (cISF) YN15-283-02, which was derived from Culicoides. The cISF-WNV chimera was constructed by replacing prME structural genes of the infectious YN15-283-02 cDNA clone with those of WNV and successfully rescued in Aedes albopictus cells. cISF-WNV was nonreplicable in vertebrate cells and nonpathogenic in type I interferon receptor (IFNAR)-deficient mice. A single-dose immunization of cISF-WNV elicited considerable Th1-biased antibody responses in C57BL/6 mice, which was sufficient to offer complete protection against lethal WNV challenge with no symptoms. Our studies demonstrated the potential of the insect-specific cISF-WNV as a prophylactic vaccine candidate to prevent infection with WNV.

Temporal Goos-Hänchen Shift in Synthetic Discrete-Time Heterolattices.

Experimental demonstration of tunable temporal Goos-Hänchen shift (GHS) in synthetic discrete-time heterolattices with scalar and vector gauge potentials is reported. By using Heaviside-function modulation in two fiber loops, we create a sharp gauge-potential interface and observe temporal GHS for total internal reflection (TIR), which manifests as a time delay rather than a spatial shift. The TIR occurs as the incident mode falls into the band gap of transmitted region with band shifting by scalar and vector potential. We find that both scalar and vector potential codetermine GHS by controlling the decay (imaginary part) and oscillation (real part) of a penetrated evanescent wave, in stark contrast to traditional spatial GHS only determined by the decay factor. We also observe diverging characteristics of GHS at band-gap edges where evanescent-to-propagating wave transition occurs. GHS for frustrated total internal reflection (FTIR) by a finite-width evanescent barrier is also demonstrated, which shows saturation properties to the single-interface TIR case under infinite-width limit. Finally, we develop an accumulation measurement method using multiple TIRs to improve the precision for measuring even tinier GHS. The study initiates precise measurement of temporal GHS for discrete-time reflections, which may feature potential applications in precise time-delay control and measurement.

DEC1 is involved in circadian rhythm disruption-exacerbated pulmonary fibrosis.

BACKGROUND: The alveolar epithelial type II cell (AT2) and its senescence play a pivotal role in alveolar damage and pulmonary fibrosis. Cell circadian rhythm is strongly associated with cell senescence. Differentiated embryonic chondrocyte expressed gene 1 (DEC1) is a very important circadian clock gene. However, the role of DEC1 in AT2 senescence and pulmonary fibrosis was still unclear. RESULTS: In this study, a circadian disruption model of light intervention was used. It was found that circadian disruption exacerbated pulmonary fibrosis in mice. To understand the underlying mechanism, DEC1 levels were investigated. Results showed that DEC1 levels increased in lung tissues of IPF patients and in bleomycin-induced mouse fibrotic lungs. In vitro study revealed that bleomycin and TGF-ß1 increased the expressions of DEC1, collagen-I, and fibronectin in AT2 cells. Inhibition of DEC1 mitigated bleomycin-induced fibrotic changes in vitro and in vivo. After that, cell senescence was observed in bleomycin-treated AT2 cells and mouse models, but these were prevented by DEC1 inhibition. At last, p21 was confirmed having circadian rhythm followed DEC1 in normal conditions. But bleomycin disrupted the circadian rhythm and increased DEC1 which promoted p21 expression, increased p21 mediated AT2 senescence and pulmonary fibrosis. CONCLUSIONS: Taken together, circadian clock protein DEC1 mediated pulmonary fibrosis via p21 and cell senescence in alveolar epithelial type II cells.

Speciation and Possible Origins of Organosulfur Compounds in Rice Paddy Soils Affected by Acid Mine Drainage.

Although sulfur cycling in acid mine drainage (AMD)-contaminated rice paddy soils is critical to understanding and mitigating the environmental consequences of AMD, potential sources and transformations of organosulfur compounds in such soils are poorly understood. We used sulfur K-edge X-ray absorption near edge structure (XANES) spectroscopy to quantify organosulfur compounds in paddy soils from five AMD-contaminated sites and one AMD-uncontaminated reference site near the Dabaoshan sulfide mining area in South China. We also determined the sulfur stable isotope compositions of water-soluble sulfate (δ34SWS), adsorbed sulfate (δ34SAS), fulvic acid sulfur (δ34SFAS), and humic acid sulfur (δ34SHAS) in these samples. Organosulfate was the dominant functional group in humic acid sulfur (HAS) in both AMD-contaminated (46%) and AMD-uncontaminated paddy soils (42%). Thiol/organic monosulfide contributed a significantly lower proportion of HAS in AMD-contaminated paddy soils (8%) compared to that in AMD-uncontaminated paddy soils (21%). Within contaminated soils, the concentration of thiol/organic monosulfide was positively correlated with cation exchange capacity (CEC), moisture content (MC), and total Fe (TFe). δ34SFAS ranged from -6.3 to 2.7‰, similar to δ34SWS (-6.9 to 8.9‰), indicating that fulvic acid sulfur (FAS) was mainly derived from biogenic S-bearing organic compounds produced by assimilatory sulfate reduction. δ34SHAS (-11.0 to -1.6‰) were more negative compared to δ34SWS, indicating that dissimilatory sulfate reduction and abiotic sulfurization of organic matter were the main processes in the formation of HAS.

Periodontal granulation tissue - To remove or not to remove, that is the question.

Formation of granulation tissue is a fundamental phase in periodontal wound healing with subsequent maturation leading to regeneration or repair. However, persistently inflamed granulation tissue presents in osseous defects as a result of periodontitis and is routinely disrupted and discarded with non-surgical and surgical therapy to facilitate wound healing or improve chances of regeneration. Histological assessment suggests that granulation tissue from periodontitis-affected sites is effectively a chronic inflammatory tissue resulting from impaired wound healing due to persistence of bacterial dysbiotic bioflim. Nevertheless, the immunomodulatory potential and stem cell characteristics in granulation tissue have also raised speculation about the tissue's regenerative potential. This has led to the conception and recent implementation of surgical techniques which preserve granulation tissue with the intention of enhancing innate regenerative potential and improve clinical outcomes. As knowledge of fundamental cellular and molecular functions regulating periodontitis-affected granulation tissue is still scarce, this review aimed to provide a summary of current understanding of granulation tissue in the context of periodontal wound healing. This may provide new insights into clinical practice related to the management of granulation tissue and stimulate further investigation.

Factors affecting long-term changes of meibomian gland in MGD patients.

PURPOSE: To explore the long-term course of patients with meibomian gland dysfunction (MGD), and to analyse potential factors affecting the recovery of meibomian gland (MG) dropout. METHODS: Seventy-nine MGD patients (79 eyes) aged 36.03±15.78 years old who underwent more than one year of follow-up were enrolled in this retrospective study. Corneal fluorescein staining (CFS), tear meniscus height (TMH), noninvasive breakup time (NIBUT), and noncontact meibography at baseline and last visit were collected and analysed. Then an automatic MG analyzer was used to measure the morphological and functional parameters of MGs, including their area ratio (AR), tortuosity index (TI), and signal index (SI). The patients whose AR increased by more than 5% were defined as MG improvement, and AR decreased by more than 5% was MG worsening. RESULTS: A total of 79 patients (79 eyes) were assessed with at least 1-year of follow-up. More than 1/3 of MGD patients (27 eyes, 34.2%) underwent MG improvement, and 30.4% of MGs became worsened. Age (P=0.002), gender (P<0.001), IPL treatment (P=0.013), the change of CFS (P=0.0015), and the recovery of SI (P=0.035) showed significant differences among different recovery groups. Age(P<0.001), female sex (P=0.003), ΔCFS (P<0.001), AR at baseline (P<0.001) were negative correlation with AR recovery, and the change of SI (P=0.003) and IPL treatment (P=0.003) had a positive correlation with it. Among them, age (P=0.038), the change of CFS (P=0.004), and AR at baseline (P=0.007) were confirmed as negatively correlated factors predicting the long-term change of the MG. CONCLUSION: Although the MGD treatment has continued for more than 1 year, only 34.2% of MGD patients were observed to undergo MG improvement. Younger patients and patients with better CFS recovery seem to have more opportunities to improve their MGs.

High-Titer Self-Propagating Capsidless Chikungunya Virus Generated in Vero Cells as a Strategy for Alphavirus Vaccine Development.

In our previous study, we found that a new type of Chikungunya virus particle with a complete capsid deletion (ΔC-CHIKV) is still infectious in BHK-21 cells and demonstrated its potential as a live attenuated vaccine candidate. However, the low yield as well as the disability to propagate in vaccine production cell line Vero of ΔC-CHIKV are not practical for commercial vaccine development. In this study, we not only achieved the successful propagation of the viral particle in Vero cells, but significantly improved its yield through construction of a chimeric VEEV-ΔC-CHIKV and extensive passage in Vero cells. Mechanistically, high production of VEEV-ΔC-CHIKV is due to the improvement of viral RNA packaging efficiency conferred by adaptive mutations, especially those in envelope proteins. Similar to ΔC-CHIKV, the passaged VEEV-ΔC-CHIKV is safe, immunogenic, and efficacious, which protects mice from CHIKV challenge after only one shot of immunization. Our study demonstrates that the utilization of infectious capsidless viral particle of CHIKV as a vaccine candidate is a practical strategy for the development of alphavirus vaccine. IMPORTANCE Chikungunya virus (CHIKV) is one of important emerging alphaviruses. Currently, there are no licensed vaccines against CHIKV infection. We have previously found a new type of Chikungunya virus particle with a complete capsid deletion (ΔC-CHIKV) as a live attenuated vaccine candidate that is not suitable for commercial vaccine development with the low viral titer production. In this study, we significantly improved its production through construction of a chimeric VEEV-ΔC-CHIKV. Our results proved the utilization of infectious capsidless viral particle of CHIKV as a safe and practical vaccine candidate.

Stress Induces Prolonged Pain Recovery After Surgery: Involvement of Glucocorticoid-Related Pathway.

BACKGROUND: Increasing evidence suggests that chronic stress increases pain sensitivity and exacerbates existing pain. However, whether and how chronic unpredictable stress (CUS) affects surgical pain is unclear. METHODS: A postsurgical pain model was performed by longitudinal incision from 0.3 cm of the proximal edge of the heel toward the toes. The skin was sutured, and the wound site was covered. Sham surgery groups underwent the same procedure without an incision. The short-term CUS procedure was conducted by exposure of mice to 2 different stressors each day for 7 days. The behavior tests were conducted between 9:00 am and 4:00 pm. Mice were killed on day 19, and the mouse bilateral L4/5 dorsal root ganglia, spinal cord, anterior cingulate and insular cortex, and amygdala were collected for immunoblot analyses. RESULTS: Presurgical exposure of mice to CUS every day for 1-7 days showed significant depression-like behavior as evidenced by reduced sucrose preference in the sucrose consumption test and prolonged immobility time in the forced swimming task. This short-term CUS procedure did not affect the basal nociceptive response to mechanical and cold stimuli in the Von Frey and acetone-induced allodynia tests, but it delayed pain recovery after surgery, as indicated by the prolonged hypersensitivity in mechanical and cold stimuli by 12 days. The subsequent studies demonstrated that this CUS caused an increase in adrenal gland index. The abnormalities in pain recovery and adrenal gland index after surgery were reversed by a glucocorticoid receptor (GR) antagonist RU38486. Moreover, the prolonged pain recovery after surgery induced by CUS seemed to involve an increase in GR expression and decreases in cyclic adenosine monophosphate, phosphorylated cAMP response element binding protein, and brain-derived neurotrophic factor levels in emotion-related brain regions, such as anterior cingulate and insular cortex, amygdala, dorsal horn, and dorsal root ganglion. CONCLUSIONS: This finding indicates that stress-induced GR change may result in dysfunction of GR-related neuroprotective pathway.

DSCC1 interacts with HSP90AB1 and promotes the progression of lung adenocarcinoma via regulating ER stress.

Lung cancer is a leading cause of cancer-related deaths, and the most common type is lung adenocarcinoma (LUAD). LUAD is frequently diagnosed in people who never smoked, patients are always diagnosed at advanced inoperable stages, and the prognosis is ultimately poor. Thus, there is an urgent need for the development of novel targeted therapeutics to suppress LUAD progression. In this study, we demonstrated that the expression of DNA replication and sister chromatid cohesion 1 (DSCC1) was higher in LUAD samples than normal tissues, and the overexpression of DSCC1 or its coexpressed genes were highly correlated with poor outcomes of LUAD patients, highlighting DSCC1 might be involved in LUAD progression. Furthermore, the expression of DSCC1 was positively correlated with multiple genetic mutations which drive cancer development, including TP53, TTN, CSMD, and etc. More importantly, DSCC1 could promote the cell proliferation, stemness, EMT, and metastatic potential of LUAD cells. In addition, DSCC1 interacted with HSP90AB1 and promoted the progression of LUAD via regulating ER stress. Meanwhile, DSCC1 expression negatively correlated with immune cell infiltration in lung cancer, and DSCC1 positively regulated the expression of PD-L1 in LUAD cells. Collectively, this study revealed that DSCC1 is a novel therapeutic target to treat LUAD and a biomarker for predicting the efficiency of PD-1/PD-L1 blockade treatment.