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Fibroblasts are stromal cells ubiquitously distributed in the body of nearly every organ tissue. These cells were previously considered to be "passive cells", solely responsible for ensuring the turnover of the extracellular matrix (ECM). However, their versatility, including their ability to switch phenotypes in response to tissue injury and dynamic activity in the maintenance of tissue specific homeostasis and integrity have been recently revealed by the innovation of technological tools such as genetically modified mouse models and single cell analysis. These highly plastic and heterogeneous cells equipped with multifaceted functions including the regulation of angiogenesis, inflammation as well as their innate stemness characteristics, play a central role in the delicately regulated process of wound healing. Fibroblast dysregulation underlies many chronic conditions, including cardiovascular diseases, cancer, inflammatory diseases, and diabetes mellitus (DM), which represent the current major causes of morbidity and mortality worldwide. Diabetic foot ulcer (DFU), one of the most severe complications of DM affects 40 to 60 million people. Chronic non-healing DFU wounds expose patients to substantial sequelae including infections, gangrene, amputation, and death. A complete understanding of the pathophysiology of DFU and targeting pathways involved in the dysregulation of fibroblasts are required for the development of innovative new therapeutic treatments, critically needed for these patients. [ABSTRACT FROM AUTHOR]

Energetic internal tides (ITs) are generated from the Luzon Strait (LS) and propagate westward into the South China Sea (SCS). Owing to the lack of large-scale synchronous measurements, the propagation features and seasonal variations of diurnal ITs remain unclear. From 2018 to 2019, mode-1 diurnal ITs west of the LS were continuously observed using a large-scale moored array of 27 pressure-recording inverted echo sounders (PIESs) and a thermistor chain. Measurements confirmed that diurnal ITs radiate from the LS with a north–south asymmetrical pattern, with the most energetic channel located in the middle and south of the LS. The total energy radiated into the SCS across 120°E is 2.67 GW for the K1 ITs and 1.54 GW for the O1 ITs, approximately 2 times larger than those inferred from satellite observations. K1 dominates among the diurnal ITs, with its maximum isopycnal displacement (amplitude) and energy input to the SCS being the strongest in summer (i.e., 16.3 m and 2.81 GW, respectively). The propagation speed of K1 is higher in summer and autumn along the main channel (i.e., 4.33and 4.36 m s−1, respectively). Seasonal stratification and circulation play important roles in the seasonal variation of amplitude and propagation speed of the K1 ITs. The seasonal variability of diurnal-band ITs, which includes all diurnal constituents, is location-dependent and primarily results from the superposition of the K1 and P1 ITs. In particular, vertical displacement is strong in summer and winter along the main channel of the K1 and P1 ITs. The seasonal amplitude of K1 can modulate this seasonal feature. Significance Statement: Internal tides (ITs) are internal waves at tidal frequencies. The Luzon Strait (LS) is one of the most energetic sites to generate large-amplitude ITs. The ITs propagate into the South China Sea (SCS), interact with mesoscale eddies, large-scale circulations, etc., and influence local hydrodynamics as well as ecosystem and sediment transport. This motivated an observation plan to investigate the ITs at the western entrance of the LS. From June 2018 to August 2019, an array of 28 PIESs was deployed in the northeastern SCS, almost covering the western entrance of the LS, to investigate the propagation properties of ITs including their amplitude, phase speed, wavelength, propagation direction, and energy fluxes and their annual and seasonal variations. Here, we primarily focus on the mode-1 diurnal ITs. The new insights enrich our understanding of IT dynamics and seasonal variations and support further improvements in numerical simulations. [ABSTRACT FROM AUTHOR]

Using observational and reanalysis data sets, we investigated interannual variability in the Kuroshio in the East China Sea (ECS‐Kuroshio). We exhibited that the surface velocity and position of the ECS‐Kuroshio were synchronized on a quasi‐3‐year interannual timescale during 2005–2016. We further demonstrated that: (a) during 2005–2016, wind stress curl variability related to the El Niño–Southern Oscillation (ENSO) played a leading role in the interannual ECS‐Kuroshio variability by exciting baroclinic Rossby waves along the subtropical countercurrent (STCC) zone east of Taiwan; (b) mesoscale eddy activities in the STCC zone, especially long‐lived (≥150‐day lifetime) cyclonic eddies, probably played a secondary role in the interannual ECS‐Kuroshio variability. In addition, we showed that the occurrence of the quasi‐3‐year interannual variability of the ECS‐Kuroshio since 2005 was likely linked to the following changes in the ENSO‐related atmospheric circulation: (a) The primary ENSO timescale changed from a quasi‐5‐year period in 1993–2004 to a quasi‐3‐year one in 2005–2016; (b) Over the central equatorial Pacific along with the eastern tropical Indian Ocean, the sea surface temperature in 2005–2016 varied with a more intense amplitude than in 1993–2004, which resulted in a different western North Pacific atmospheric response to the ENSO in 2005–2016 from that in 1993–2004. Plain Language Summary: The Kuroshio, which serves as the western boundary current of the North Pacific subtropical gyre, is one of the most important elements that control the oceanic and atmospheric conditions around the East China Sea (ECS). In this study, we found that the surface velocity and position of the ECS‐Kuroshio were synchronized on a quasi‐3‐year interannual timescale during 2005–2016. We further determined that, during 2005–2016, baroclinic Rossby waves along the subtropical countercurrent (STCC) zone east of Taiwan, which were excited by wind forcings related to the El Niño–Southern Oscillation (ENSO), played a leading role in the interannual ECS‐Kuroshio variability, and mesoscale eddy activities in the STCC zone probably played a secondary role. Moreover, we suggested that, since the mid‐2000s, the change of the primary ENSO timescale and the amplification of the sea surface temperature variability in the tropical ocean have led to the occurrence of the quasi‐3‐year interannual variability of the ECS‐Kuroshio through the western North Pacific atmospheric response to the ENSO. Key Points: Kuroshio in the East China Sea varied on a quasi‐3‐year interannual timescale during 2005–2016El Niño–Southern Oscillation‐related atmospheric circulation played a leading role in this interannual variability by exciting baroclinic Rossby wavesMesoscale eddy activities, especially long‐lived (≥150‐day) cyclonic eddies, probably contributed secondarily to this interannual variability [ABSTRACT FROM AUTHOR]

Using a large-scale observation array of 27 simultaneous pressure-recording inverted echo sounders (PIESs), the standing wave features of the mode-1 M2 internal tide west of the Luzon Strait (LS) were identified. These features exhibited nonmonotonic spatial phase shifts and half-wavelength amplitude modulation, resulting in spatially varying amplitudes under PIES observations, which have not been previously observed in field observations west of the LS. Satellite altimeter measurements also identified standing-wave patterns consistent with the PIES observations. These patterns emanated from interference between the northwestward and southeastward beams from the LS and the slope of the southern Taiwan Strait, respectively. Near the LS, the two beams superimposed into partial standing waves, whereas the superimposed waves tended to become perfect standing waves near the slope of the southern Taiwan Strait. The nodes and antinodes of the wave shifted under the influence of an anticyclonic eddy. The eddy-induced background current modified the phase speed of the internal tides, and the superimposed standing-wave nodes and antinodes deflected clockwise. The node shifted during three anticyclonic eddy events, and two stations on two sides of the wave node showed opposite variations in amplitude. Significance Statement: The internal tidal constituent (M2) propagating in opposite directions can result in standing waves, which have been frequently observed in global oceans but were absent west of the Luzon Strait (LS). Our observations (based on a large-scale array west of the LS) discovered a standing M2 internal tide, which stems from interference between the northwestward beams emanating from the LS and southeastward beams from the slope of the southern Taiwan Strait. Anticyclonic eddies play important roles in adjusting the amplitude of internal tides by deflecting the standing-wave nodes and antinodes clockwise. The study facilitates the understanding of the energy distribution and mixing processes west of the LS and provides a fresh perspective on the dynamic relationship between mesoscale perturbations and internal tides. [ABSTRACT FROM AUTHOR]

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The response to ischemia in peripheral artery disease (PAD) depends on compensatory neovascularization and coordination of tissue regeneration. Identifying novel mechanisms regulating these processes is critical to the development of nonsurgical treatments for PAD. E-selectin is an adhesion molecule that mediates cell recruitment during neovascularization. Therapeutic priming of ischemic limb tissues with intramuscular E-selectin gene therapy promotes angiogenesis and reduces tissue loss in a murine hindlimb gangrene model. In this study, we evaluated the effects of E-selectin gene therapy on skeletal muscle recovery, specifically focusing on exercise performance and myofiber regeneration. C57BL/6J mice were treated with intramuscular E-selectin/adeno-associated virus serotype 2/2 gene therapy (E-sel/AAV) or LacZ/AAV2/2 (LacZ/AAV) as control and then subjected to femoral artery coagulation. Recovery of hindlimb perfusion was assessed by laser Doppler perfusion imaging and muscle function by treadmill exhaustion and grip strength testing. After three postoperative weeks, hindlimb muscle was harvested for immunofluorescence analysis. At all postoperative time points, mice treated with E-sel/AAV had improved hindlimb perfusion and exercise capacity. E-sel/AAV gene therapy also increased the coexpression of MyoD and Ki-67 in skeletal muscle progenitors and the proportion of Myh7+ myofibers. Altogether, our findings demonstrate that in addition to improving reperfusion, intramuscular E-sel/AAV gene therapy enhances the regeneration of ischemic skeletal muscle with a corresponding benefit on exercise performance. These results suggest a potential role for E-sel/AAV gene therapy as a nonsurgical adjunct in patients with life-limiting PAD. [ABSTRACT FROM AUTHOR]

The complete mitochondrial genome (mitogenome) of Eriogyna pyretorum (Lepidoptera: Saturniidae) was determined as being composed of 15,327 base pairs (bp), including 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes, and a control region. The arrangement of the PCGs is the same as that found in the other sequenced lepidopteran. The AT skewness for the E. pyretorum mitogenome is slightly negative (-0.031), indicating the occurrence of more Ts than As. The nucleotide composition of the E. pyretorum mitogenome is also biased toward A + T nucleotides (80.82%). All PCGs are initiated by ATN codons, except for cytochrome c oxidase subunit 1 and 2 (cox1 and cox2). Two of the 13 PCGs harbor the incomplete termination codon by T. All tRNA genes have a typical clover-leaf structure of mitochondrial tRNA, with the exception of trnS1(AGN) and trnS2(UCN). Phylogenetic analysis among the available lepidopteran species supports the current morphology-based hypothesis that Bombycoidea, Geometroidea, Notodontidea, Papilionoidea and Pyraloidea are monophyletic. As has been previously suggested, Bombycidae (Bombyx mori and Bombyx mandarina), Sphingoidae (Manduca sexta) and Saturniidae (Antheraea pernyi, Antheraea yamamai, E. pyretorum and Caligula boisduvalii) formed a group.

In this study we successfully constructed a full-length cDNA library from Chinese oak silkworm, Antheraea pernyi, the most well-known wild silkworm used for silk production and insect food. Total RNA was extracted from a single fresh female pupa at the diapause stage. The titer of the library was 5 × 105 cfu/ml and the proportion of recombinant clones was approximately 95%. Expressed sequence tag (EST) analysis was used to characterize the library. A total of 175 clustered ESTs consisting of 24 contigs and 151 singlets were generated from 250 effective sequences. Of the 175 unigenes, 97 (55.4%) were known genes but only five from A. pernyi, 37 (21.2%) were known ESTs without function annotation, and 41 (23.4%) were novel ESTs. By EST sequencing, a gene coding KK-42-binding protein in A. pernyi (named as ApKK42-BP; GenBank accession no. FJ744151) was identified and characterized. Protein sequence analysis showed that ApKK42-BP was not a membrane protein but an extracellular protein with a signal peptide at position 1-18, and contained two putative conserved domains, abhydro_lipase and abhydrolase_1, suggesting it may be a member of lipase superfamily. Expression analysis based on number of ESTs showed that ApKK42-BP was an abundant gene in the period of diapause stage, suggesting it may also be involved in pupa-diapause termination.

Linear trends in the Ryukyu Current, a part of the western boundary current in the western North Pacific flowing on the seaside of the Ryukyu Island chain, were investigated using reanalysis data during 1993–2018. The subsurface Ryukyu Current has weakened along its path during the recent decades. Two determinant factors for the weakened subsurface Ryukyu Current are as follows. First, the first baroclinic topographic Rossby wave propagated signals emanating from the Tokara Strait (TK) and the Kerama Gap (KG) southward along the eastern slope of the Ryukyu Island chain, which depressed the onshore side of the isopycnal. The weakened Kuroshio in the TK and weakened overflow through the KG during this period led to isopycnal shoaling along the onshore side east of the Ryukyu Island chain, slowing down the Ryukyu Current. Second, anticyclonic eddies emanated from the interior region near 30°N and 170°W increased during this period. These anticyclonic eddies, translating southwestward, reached east of the Ryukyu Island chain, and finally deepened the offshore side of the isopycnal depth of the Ryukyu Current. The isopycnal across the Ryukyu Current velocity core became less steep, thereby weakening the subsurface Ryukyu Current. Moreover, a positive trend of sea surface height anomaly southeast of Miyakojima, driven by wind stress changes in high latitudes (near the Kuroshio Extension band), strengthened the northward current in the upper layer southeast of Miyakojima. Plain Language Summary: The Ryukyu Current is part of the western boundary current of the North Pacific subtropical gyre on the eastern slope of the Ryukyu Island chain. This study revealed that the Ryukyu Current subsurface velocity core underwent a noticeable weakening trend during 1993–2018. The weakened Ryukyu Current was instigated by the combined effect of the topographic Rossby wave originating in the straits (e.g., the Tokara Strait and Kerama Gap) of the Ryukyu Island chain, and the increasing anticyclonic eddy emanating from the interior region east of the Kuroshio Extension. The former processes led the onshore side of the isopycnal to shoal, while the latter process induces the isopycnal to deepen on the offshore side. The isopycnal near the Ryukyu Current velocity core becomes less steep, thereby weakening the subsurface Ryukyu Current. Key Points: The Ryukyu Current, part of the western boundary current of the North Pacific, tended to weaken along its path during 1993–2018The weakened Kuroshio in the Tokara Strait is one determinant for the weakened Ryukyu Current subsurface coreIncreasing anticyclonic eddies emanating from the interior region east of the Kuroshio Extension render a weakened Ryukyu Current [ABSTRACT FROM AUTHOR]

To accurately reconstruct large-area three-dimensional current fields in coastal regions, simultaneous observations with ten coastal acoustic tomography (CAT) stations and two high-frequency radar (HFR) stations were performed in the Xiangshan Bay (XSB) on 4–5 December 2020. The section-averaged velocity that was observed by CAT and the radial velocity that was observed by HFR were, for the first time, synchronously assimilated into a three-dimensional barotropic ocean model. Compared with acoustic Doppler current profile data, the velocities of the model assimilating both CAT and HFR data had the highest accuracy according to root mean square differences (RMSDs), ranging from 0.05 to 0.08 m/s for all the vertical layers. For the models individually assimilating CAT and HFR, the values in the vertical layers ranged from 0.07 to 0.12 m/s and 0.08 to 0.13 m/s, respectively. A harmonic analysis of the model grid data showed that the spatial mean amplitudes of the M2, M4, and residual currents were 0.66, 0.14, and 0.09 m/s, respectively. Furthermore, the standing wave characteristics of the M2 current and M4 associated-oscillation in the inner XSB, mouth of the Xiangshan fjord, were better captured by the model assimilating both CAT and HFR. Our study demonstrates the advances in three-dimensional tidal current analysis using a model that assimilates both CAT and HFR data, especially in regions with complex coastal geography. [ABSTRACT FROM AUTHOR]

Endothelial progenitor cells (EPCs) are essential in vasculogenesis and wound healing, but their circulating and wound level numbers are decreased in diabetes. This study aimed to determine mechanisms responsible for [...]

Melanocytes reside within the basal layer of the human epidermis, where they attach to the basement membrane and replicate at a rate proportionate to that of keratinocytes, maintaining a lifelong stable ratio. In this study, we report that coculturing melanocytes with keratinocytes up-regulated CCN3, a matricellular protein that we subsequently found to be critical for the spatial localization of melanocytes to the basement membrane. CCN3 knockdown cells were dissociated either upward to the suprabasal layers of the epidermis or downward into the dermis. The overexpression of CCN3 increased adhesion to collagen type IV, the major component of the basement membrane. As the receptor responsible for CCN3-mediated melanocyte localization, we identified discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase that acts as a collagen IV adhesion receptor. DDR1 knockdown decreased melanocyte adhesion to collagen IV and shifted melanocyte localization in a manner similar to CCN3 knockdown. These results demonstrate an intricate and necessary communication between keratinocytes and melanocytes in maintaining normal epidermal homeostasis.

Linear trends in Kuroshio transport during a recent global warming hiatus (1998–2013) were evaluated using long‐term ferryboat ADCP (acoustic Doppler current profiler) data and tidal gauge data in the Tokara Strait south of Japan. The Kuroshio exhibited a remarkable weakening trend of approximately 0.05 Sv year−1 (1 Sv = 106 m3 s−1). The pycnocline in the weakened Kuroshio was relaxed and displayed shoaling at the offshore edge, which was attributed to vertical thermocline displacement rather than to water mass modification. Importantly, Kuroshio transport trends in the Tokara Strait were affected by sea surface height anomalies, which were driven by the combined effects of the clockwise baroclinic‐mode coastal trapped wave propagation along the southern coast of Japan and downstream Kuroshio advection in the East China Sea. Both features were induced by wind stress curl changes related to the global warming hiatus over the North Pacific. Plain Language Summary: The Kuroshio is the western boundary current in the wind‐driven subtropical circulation of the North Pacific. It exits the East China Sea and flows into the North Pacific through the Tokara Strait between the Yakushima and Amami Oshima Islands to the south of Kyushu, Japan. This study revealed that the Kuroshio transport through the Tokara Strait showed a remarkable weakening trend along with a northward shift during 1998–2013. Changes in the wind stress curl in the high (low)‐latitude band over the North Pacific during the global warming hiatus exhibited negative (positive) tendencies, leading to anomalously high (low) sea surface heights. The high (low) sea surface height anomaly arrived at the onshore (offshore) side of Tokara Strait from the high (low)‐latitude band decreasing Kuroshio transport because of geostrophy. Key Points: Kuroshio transport in the Tokara Strait south of Japan decreased by ∼4% during 1998–2013, indicating a rate of about 0.05 Sv year−1Shoaling of the offshore pycnocline in the Kuroshio was due to vertical thermocline displacement rather than to modified water massDynamic‐topography propagation pathways from the northern and southern interior regions caused weakened Kuroshio transport in the hiatus [ABSTRACT FROM AUTHOR]

Topographic Rossby waves (TRWs) are oscillations generated on sloping topography when water columns travel across isobaths under potential vorticity conservation. From our large-scale observations from 2016 to 2019, near-65-day TRWs were first observed in the deep basin of the South China Sea (SCS). The TRWs propagated westward with a larger wavelength (235 km) and phase speed (3.6 km day−1) in the north of the array and a smaller wavelength (80 km) and phase speed (1.2 km day−1) toward the southwest of the array. The ray-tracing model was used to identify the energy source and propagation features of the TRWs. The paths of the near-65-day TRWs mainly followed the isobaths with a slightly downslope propagation. The possible energy source of the TRWs was the variance of surface eddies southwest of Taiwan. The near-65-day energy propagated from the southwest of Taiwan to the northeast and southwest of the array over ~100–120 and ~105 days, respectively, corresponding to a group velocity of 4.2–5.0 and 10.5 km day−1, respectively. This suggests that TRWs play an important role in deep-ocean dynamics and deep current variation, and upper-ocean variance may adjust the intraseasonal variability in the deep SCS. Significance Statement: Topographic Rossby waves (TRWs) play an important role in deep-ocean dynamics and deep current variation, and they have potential impacts on sediment transport and abyssal biogeochemical processes. From large-scale observations of abyssal currents in the deep basin of the South China Sea (SCS), energetic near-65-day TRWs with a westward phase speed of 1.2–3.6 km day−1 were first observed. The ray-tracing model was used to identify the energy source and propagation features of the TRWs. The possible energy source was the variation of mesoscale eddies southwest of Taiwan. The study has implications for adjustments to the energy and intraseasonal variability generation in the deep basin of the SCS. [ABSTRACT FROM AUTHOR]