Brillouin Klein space and half-turn space in three-dimensional acoustic crystals.

The Bloch band theory and Brillouin zone (BZ) that characterize wave-like behaviors in periodic mediums are two cornerstones of contemporary physics, ranging from condensed matter to topological physics. Recent theoretical breakthrough revealed that, under the projective symmetry algebra enforced by artificial gauge fields, the usual two-dimensional (2D) BZ (orientable Brillouin two-torus) can be fundamentally modified to a non-orientable Brillouin Klein bottle with radically distinct manifold topology. However, the physical consequence of artificial gauge fields on the more general three-dimensional (3D) BZ (orientable Brillouin three-torus) was so far missing. Here, we theoretically discovered and experimentally observed that the fundamental domain and topology of the usual 3D BZ can be reduced to a non-orientable Brillouin Klein space or an orientable Brillouin half-turn space in a 3D acoustic crystal with artificial gauge fields. We experimentally identify peculiar 3D momentum-space non-symmorphic screw rotation and glide reflection symmetries in the measured band structures. Moreover, we experimentally demonstrate a novel stacked weak Klein bottle insulator featuring a nonzero Z2 topological invariant and self-collimated topological surface states at two opposite surfaces related by a nonlocal twist, radically distinct from all previous 3D topological insulators. Our discovery not only fundamentally modifies the fundamental domain and topology of 3D BZ, but also opens the door towards a wealth of previously overlooked momentum-space multidimensional manifold topologies and novel gauge-symmetry-enriched topological physics and robust acoustic wave manipulations beyond the existing paradigms.

Deforestation in Latin America in the 2000s predominantly occurred outside of typical mature forests.

The role of tropical forests in the global carbon budget remains controversial, as carbon emissions from deforestation are highly uncertain. This high uncertainty arises from the use of either fixed forest carbon stock density or maps generated from satellite-based optical reflectance with limited sensitivity to biomass to generate accurate estimates of emissions from deforestation. New space missions aiming to accurately map the carbon stock density rely on direct measurements of the spatial structures of forests using lidar and radar. We found that lost forests are special cases, and their spatial structures can be directly measured by combining archived data acquired before and after deforestation by space missions principally aimed at measuring topography. Thus, using biomass mapping, we obtained new estimates of carbon loss from deforestation ahead of forthcoming space missions. Here, using a high-resolution map of forest loss and the synergy of radar and lidar to estimate the aboveground biomass density of forests, we found that deforestation in the 2000s in Latin America, one of the severely deforested regions, mainly occurred in forests with a significantly lower carbon stock density than typical mature forests. Deforestation areas with carbon stock densities lower than 20.0, 50.0, and 100.0 Mg C/ha accounted for 42.1%, 62.0%, and 83.3% of the entire deforested area, respectively. The average carbon stock density of lost forests was only 49.13 Mg C/ha, which challenges the current knowledge on the carbon stock density of lost forests (with a default value 100 Mg C/ha according to the Intergovernmental Panel on Climate Change Tier 1 estimates, or approximately 112 Mg C/ha used in other studies). This is demonstrated over both the entire region and the footprints of the spaceborne lidar. Consequently, our estimate of carbon loss from deforestation in Latin America in the 2000s was 253.0 ± 21.5 Tg C/year, which was considerably less than existing remote-sensing-based estimates, namely 400-600 Tg C/year. This indicates that forests in Latin America were most likely not a net carbon source in the 2000s compared to established carbon sinks. In previous studies, considerable effort has been devoted to rectify the underestimation of carbon sinks; thus, the overestimation of carbon emissions should be given sufficient consideration in global carbon budgets. Our results also provide solid evidence for the necessity of renewing knowledge on the role of tropical forests in the global carbon budget in the future using observations from new space missions.

Mechanisms of Swallowing, Speech and Voice Disorders in Parkinson's Disease: Literature Review with Our First Evidence for the Periperal Nervous System Involvement.

The majority of patients with Parkinson's disease (PD) develop swallowing, speech, and voice (SSV) disorders. Importantly, swallowing difficulty or dysphagia and related aspiration are life-threatening conditions for PD patients. Although PD treatments have significant therapeutic effects on limb motor function, their effects on SSV disorders are less impressive. A large gap in our knowledge is that the mechanisms of SSV disorders in PD are poorly understood. PD was long considered to be a central nervous system disorder caused by the death of dopaminergic neurons in the basal ganglia. Aggregates of phosphorylated α-synuclein (PAS) underlie PD pathology. SSV disorders were thought to be caused by the same dopaminergic problem as those causing impaired limb movement; however, there is little evidence to support this. The pharynx, larynx, and tongue play a critical role in performing upper airway (UA) motor tasks and their dysfunction results in disordered SSV. This review aims to provide an overview on the neuromuscular organization patterns, functions of the UA structures, clinical features of SSV disorders, and gaps in knowledge regarding the pathophysiology underlying SSV disorders in PD, and evidence supporting the hypothesis that SSV disorders in PD could be associated, at least in part, with PAS damage to the peripheral nervous system controlling the UA structures. Determining the presence and distribution of PAS lesions in the pharynx, larynx, and tongue will facilitate the identification of peripheral therapeutic targets and set a foundation for the development of new therapies to treat SSV disorders in PD.

Topological antichiral surface states in a magnetic Weyl photonic crystal.

Chiral edge states that propagate oppositely at two parallel strip edges are a hallmark feature of Chern insulators which were first proposed in the celebrated two-dimensional (2D) Haldane model. Subsequently, counterintuitive antichiral edge states that propagate in the same direction at two parallel strip edges were discovered in a 2D modified Haldane model. Recently, chiral surface states, the 2D extension of one-dimensional (1D) chiral edge states, have also been observed in a photonic analogue of a 3D Haldane model. However, despite many recent advances in antichiral edge states and chiral surface states, antichiral surface states, the 2D extension of 1D antichiral edge states, have never been realized in any physical system. Here, we report the experimental observation of antichiral surface states by constructing a 3D modified Haldane model in a magnetic Weyl photonic crystal with two pairs of frequency-shifted Weyl points (WPs). The 3D magnetic Weyl photonic crystal consists of gyromagnetic cylinders with opposite magnetization in different triangular sublattices of a 3D honeycomb lattice. Using microwave field-mapping measurements, unique properties of antichiral surface states have been observed directly, including the antichiral robust propagation, tilted surface dispersion, a single open Fermi arc connecting two projected WPs and a single Fermi loop winding around the surface Brillouin zone (BZ). These results extend the scope of antichiral topological states and enrich the family of magnetic Weyl semimetals.

Focal Application of Neurotrophic Factors Augments Outcomes of Nerve-Muscle-Endplate Grafting Technique for Limb Muscle Reinnervation.

BACKGROUND: We have developed a novel muscle reinnervation technique called "nerve-muscle-endplate grafting (NMEG) in the native motor zone (NMZ)." This study aimed to augment the outcomes of the NMEG-NMZ (NN) by focal application of exogenous neurotrophic factors (ENFs) for limb reinnervation. METHODS: Adult rats were used to conduct NN plus ENF (NN/ENF) and autologous nerve grafting (ANG, technique control). The nerve innervating the left tibialis anterior (TA) muscle was resected and the denervated TA was immediately treated with NN/ENF or ANG. For NN procedure, an NMEG pedicle was taken from the lateral gastrocnemius muscle and transferred to the NMZ of the denervated TA. For ANG, the nerve gap was bridged with sural nerve. Three months after treatment, the extent of functional and neuromuscular recovery was assessed by measuring static toe spread, maximal muscle force, wet muscle weight, regenerated axons, and innervated motor endplates (MEPs). RESULTS: NN/ENF resulted in 90% muscle force recovery of the treated TA, which is far superior to ANG (46%) and NN alone (79%) as reported elsewhere. Toe spread recovered up to 89 and 49% of the control for the NN/ENF and ANG groups, respectively. The average wet muscle weight was 87 and 52% of the control for muscles treated with NN/ENF and ANG, respectively. The mean number of the regenerated axons was 88% of the control for the muscles treated with NN/ENF, which was significantly larger than that for the ANG-repaired muscles (39%). The average percentage of the innervated MEPs in the NN/ENF-treated TA (89%) was higher compared with that in the ANG-repaired TA (48%). CONCLUSION: ENF enhances nerve regeneration and MEP reinnervation that further augment outcomes of NN. The NN technique could be an alternative option to treat denervated or paralyzed limb muscles caused by traumatic nerve injuries or lesions.

Reinnervation of Paralyzed Limb Muscle by Nerve-Muscle-Endplate Grafting Technique.

BACKGROUND: We have developed a novel reinnervation technique called nerve-muscle-endplate grafting in the native motor zone (NMEG-NMZ). However, it remains unknown whether the NMEG-NMZ is effective for limb reinnervation. OBJECTIVE: To evaluate the efficacy of the NMEG-NMZ in limb muscle reinnervation. METHODS: Forty-five adult rats were divided into 3 groups: NMEG, end-to-end anastomosis (EEA, technique control), and denervation control (DC). The left tibialis anterior muscle was denervated by resecting its nerve. For NMEG-NMZ, the denervated tibialis anterior was reinnervated by transferring a NMEG pedicle from the lateral gastrocnemius muscle. Three months after surgery, static toe spread analysis was performed for all rats and muscle force was measured for the rats treated with NMEG and EEA. Muscle weight, myofiber morphology, regenerated axons, and reinnervated motor endplates in the treated muscles were also quantified and compared with those in the DC group. RESULTS: NMEG-NMZ technique resulted in better muscle force recovery (79% of the control) compared with EEA (51% of the control, P = .048). Toe spread analysis in NMEG-NMZ reinnervated muscles showed static sciatic index = -16.8, whereas -41.4 in EEA, P < .0001). The average weight of the NMEG-NMZ reinnervated muscles (86%) was greater than those of the EEA treated (71%) and DC (26%) muscles (all P < .0001). The mean count of the regenerated axons in the muscles with NMEG-NMZ was 76% of the control, which was larger than that in the muscles with EEA (46%), P < .0001. CONCLUSION: NMEG-NMZ technique has unique advantages and is superior to EEA for muscle reinnervation and functional recovery.

Spinful Topological Phases in Acoustic Crystals with Projective PT Symmetry.

For the classification of topological phases of matter, an important consideration is whether a system is spinless or spinful, as these two classes have distinct symmetry algebra that gives rise to fundamentally different topological phases. However, only recently has it been realized theoretically that in the presence of gauge symmetry, the algebraic structure of symmetries can be projectively represented, which possibly enables the switch between spinless and spinful topological phases. Here, we report the experimental demonstration of this idea by realizing spinful topological phases in "spinless" acoustic crystals with projective space-time inversion symmetry. In particular, we realize a one-dimensional topologically gapped phase characterized by a 2Z winding number, which features double-degenerate bands in the entire Brillouin zone and two pairs of degenerate topological boundary modes. Our Letter thus overcomes a fundamental constraint on topological phases by spin classes.

Observation of Dirac Hierarchy in Three-Dimensional Acoustic Topological Insulators.

Dirac cones (DCs) play a pivotal role in various unique phenomena ranging from massless electrons in graphene to robust surface states in topological insulators (TIs). Recent studies have theoretically revealed a full Dirac hierarchy comprising an eightfold bulk DC, a fourfold surface DC, and a twofold hinge DC, associated with a hierarchy of topological phases including first-order to third-order three-dimensional (3D) topological insulators, using the same 3D base lattice. Here, we report the first experimental observation of the Dirac hierarchy in 3D acoustic TIs. Using acoustic measurements, we unambiguously reveal that lifting of multifold DCs in each hierarchy can induce two-dimensional topological surface states with a fourfold DC in a first-order 3D TI, one-dimensional topological hinge states with a twofold DC in a second-order 3D TI, and zero-dimensional topological corner states in a third-order 3D TI. Our Letter not only expands the fundamental research scope of Dirac physics, but also opens up a new route for multidimensional robust wave manipulation.

Novel CT based clinical nomogram comparable to radiomics model for identification of occult peritoneal metastasis in advanced gastric cancer.

BACKGROUND: Occult peritoneal metastasis (OPM) in advanced gastric cancer (AGC) patients remains a major diagnostic challenge. The aim of this study was to develop novel predictive models for identification of OPM in AGCs. METHOD: A total of 810 patients with primary AGCs from two hospitals were retrospectively selected and divided into training (n = 393), internal validation (n = 215) and external validation cohorts (n = 202). CT based machine learning models were built and tested to predict the OPM status in AGCs., which are 1) Radiomic signatures: using venous CT imaging features, 2) Clinical models: integrating tumor location, differentiation and extent of serosal exposure, and 3) Radiomics models: combining of radiomic signature, tumor location and tumor differentiation. RESULT: Total incidence of OPM was 8.27% (67/810). Clinical models yielded comparable classification accuracy with the corresponding radiomics models with similar AUCs (0.902-0.969 vs. 0.896-0.975) while the radiomic signatures showed relatively low AUCs of 0.863-0.976. In the case where the specificity is higher than 90%, the overall sensitivity of clinical model and radiomics model for OPM positive cases was 76.1% (51/67) and 82.1% (55/67). A nomogram based on the logistic clinical model was drawn to facilitate the usage and verification of the clinical model. CONCLUSION: Both the novel CT based clinical nomogram and radiomics model provide promising method to yield high accuracy in identification of OPM in AGC patients.

Morphometric and Immunohistochemical Characteristics of the Adult Human Soft Palate Muscles.

The soft palate is the only structure that reversibly separates the respiratory and gastrointestinal systems. Most species can eat and breathe at the same time. Humans cannot do this and malfunction of the soft palate may allow food to enter the lungs and cause fatal aspiration pneumonia. Speech is the most defining characteristic of humans and the soft palate, along with the larynx and tongue, plays the key roles. In addition, palatal muscles are involved in snoring and obstructive sleep apnea. Considering the significance of the soft palate, its function is insufficiently understood. The objectives of this study were to document morphometric and immunohistochemical characteristics of adult human soft palate muscles, including fiber size, the fiber type, and myosin heavy chain (MyHC) composition for better understanding muscle functions. In this study, 15 soft palates were obtained from human autopsies. The palatal muscles were separated, cryosectioned, and stained using histological and immunohistochemical techniques. The results showed that there was a fast type II predominance in the musculus uvulae and palatopharyngeus and a slow type I predominance in the levator veli palatine. Approximately equal proportions of type I and type II fibers existed in both the palatoglossus and tensor veli palatine. Soft palate muscles also contained hybrid fibers and some specialized myofibers expressing slow-tonic and embryonic MyHC isoforms. These findings would help better understand muscle functions.

Limb Muscle Reinnervation with the Nerve-Muscle-Endplate Grafting Technique: An Anatomical Feasibility Study.

BACKGROUND: Peroneal nerve injuries results in tibialis anterior (TA) muscle paralysis. TA paralysis could cause "foot drop," a disabling condition that can make walking difficult. As current treatment methods result in poor functional recovery, novel treatment approaches need to be studied. The aim of this study was to explore anatomical feasibility of limb reinnervation with our recently developed nerve-muscle-endplate grafting (NMEG) in the native motor zone (NMZ). METHODS: As the NMEG-NMZ technique involves in nerves and motor endplates (MEPs), the nerve supply patterns and locations of the MEP bands within the gastrocnemius (GM) and TA muscles of rats were investigated using Sihler's stain and whole-mount acetylcholinesterase (AChE) staining, respectively. Five adult rats underwent TA nerve transaction. The denervated TA was reinnervated by transferring an NMEG pedicle from the ipsilateral lateral GM. At the end of a 3-month recovery period, maximal muscle force was measured to document functional recovery. RESULTS: The results showed that the TA was innervated by the deep peroneal nerve. A single MEP band was located obliquely in the middle of the TA. The GM was composed of two neuromuscular compartments, lateral (GM-l) and medial (GM-m), each of which was innervated by a separate nerve branch derived from the tibial nerve and had a vertically positioned MEP band. The locations of MEP bands in the GM and TA muscles and nerve supply patterns demonstrated that an NMEG pedicle can be harvested from the GM-l and implanted into the NMZ within the TA muscle. The NMEG-NMZ pilot study showed that this technique resulted in optimal muscle force recovery. CONCLUSION: NMEG-NMZ surgery is feasible for limb reinnervation. Specifically, the denervated TA caused by peroneal nerve injuries can be reinnervated with a NMEG from the GM-l.

Hollow InVO4 Nanocuboid Assemblies toward Promoting Photocatalytic N2 Conversion Performance.

The unique InVO4 mesocrystal superstructure, particularly with cubical skeleton and hollow interior, which consists of numerous nanocube building blocks, closely stacking by stacking, aligning by aligning, and sharing the same crystallographic orientations, is successfully fabricated. The synergy of a reaction-limited aggregation and an Ostwald ripening process is reasonably proposed for the growth of this unique superstructure. Both single-particle surface photovoltage and confocal fluorescence spectroscopy measurements demonstrate that the long-range ordered mesocrystal superstructures can significantly retard the recombination of electron-hole pairs through the creation of a new pathway for anisotropic electron flow along the inter-nanocubes. This promising charge mobility feature of the superstructure greatly contributes to the pronounced photocatalytic performance of the InVO4 mesocrystal toward fixation of N2 into NH3 with the quantum yield of 0.50% at wavelength of 385 nm.

CT-based radiomics nomogram for preoperative prediction of No.10 lymph nodes metastasis in advanced proximal gastric cancer.

INTRODUCTION: Preoperative diagnosis of No.10 lymph nodes (LNs) metastases in advanced proximal gastric cancer (APGC) patients remains a challenge. The aim of this study was to develop a CT-based radiomics nomogram for identification of No.10 LNs status in APGCs. MATERIALS AND METHODS: A total of 515 patients with primary APGCs were retrospectively selected and divided into a training cohort (n = 340) and a validation cohort (n = 175). Total incidence of No.10 LNM was 12.4% (64/515). CT based radiomics nomogram combining with radiomic signature calculated from venous CT imaging features and CT-defined No.10 LNs status evaluated by radiologists was built and tested to predict the No.10 LNs status in APGCs. RESULTS: CT based radiomics nomogram yielded classification accuracy with areas under ROC curves, AUC = 0.896 and 0.814 in training and validation cohort, respectively, while radiomic signature and radiologist' diagnosis based on contrast-enhanced CT images yielded lower AUCs ranging in 0.742-0.866 and 0.619-0.685, respectively. In the specificity higher than 80%, the sensitivity of using radiomics nomogram, radiomic signature and radiologists' evaluation to detect No.10 LNs positive cases was 82.8% (53/64), 67.2% (43/64) and 39.1% (25/64), respectively. CONCLUSIONS: The CT-based radiomics nomogram provides a promising and more effective method to yield high accuracy in identification of No.10 LNs metastases in APGC patients.

Innervation of human soft palate muscles.

Our objective was to determine the branching and distribution of the motor nerves supplying the human soft palate muscles. Six adult specimens of the soft palate in continuity with the pharynx, larynx, and tongue were processed with Sihler's stain, a technique that can render large specimens transparent while counterstaining their nerves. The cranial nerves were identified and dissection followed their branches as they divided into smaller divisions toward their terminations in individual muscles. The results showed that both the glossopharyngeal (IX) and vagus (X) nerves have three distinct branches, superior, middle, and inferior. Only the middle branches of each nerve contributed to the pharyngeal plexus to which the facial nerve also contributed. The pharyngeal plexus was divided into two parts, a superior innervating the palatal and neighboring muscles and an inferior innervating pharyngeal constrictors. The superior branches of the IX and X nerves contributed innervation to the palatoglossus, whereas their middle branches innervated the palatopharyngeus. The palatoglossus and palatopharyngeus muscles appeared to be composed of at least two neuromuscular compartments. The lesser palatine nerve not only supplied the palatal mucosa and palatine glandular tissue but also innervated the musculus uvulae, palatopharyngeus, and levator veli palatine. The latter muscle also received its innervation from the superior branch of X nerve. The findings would be useful for better understanding the neural control of the soft palate and for developing novel neuromodulation therapies to treat certain upper airway disorders such as obstructive sleep apnea.

Antimicrobial peptide AR-23 derivatives with high endosomal disrupting ability enhance poly(l-lysine)-mediated gene transfer.

BACKGROUND: pH-sensitive peptides are a relatively new strategy for conquering the poor endosomal release of cationic polymer-mediated transfection. Modification of antimicrobial peptides by exchanging positively-charged residues with negatively-charged glutamic acid residues (Glu) greatly improves its lytic activity at the endosomal pH, which could improve cationic polymer-mediated transfection. METHODS: In the present study, we investigated the effect of the number of Glu substituted for positively-charged residues on the endosomal escape activity of AR-23 and the ability of mutated AR-23 with respect to enhancing cationic polymer-mediated transfection. Three analogs were synthesized by replacing the positively-charged residues in the AR-23 sequence with Glu one-by-one. RESULTS: The pH-sensitive lysis ability of the peptides, the effect of peptides on the physicochemical characteristics, the intracellular trafficking, the transfection efficiency and the cytotoxicity of the polyplexes were determined. Increased lytic activity of peptides was observed with the increased number of Glu replacement in the AR-23 sequence at acidic pH. The number of Glu substituted for positively-charged residues of AR-23 dramatically affects its lysis ability at neutral pH. Triple-Glu substitution in the AR-23 sequence greatly improved poly(l-lysine)-mediated gene transfection efficiency at the same time as maintaining low cytotoxicity. CONCLUSIONS: The results indicate that replacement of positively-charged residues with sufficient Glu residues may be considered as a method for designing pH-sensitive peptides, which could be applied as potential enhancers for improving cationic polymer-mediated transfection.

Evaluation of the Therapeutic Effect of Magneto-Nanomicelles Based on Magneto-Thermal and Photo-Thermal Therapy.

In this study, we investigated the hyperthermia efficiency of magnetic hyperthermia therapy (MHT), photo-thermal therapy (PTT), and the combination of both techniques by employing SPIO-based magneto-nanomicelles as the heating agents. Magneto-nanomicelles in aqueous suspension were exposed to 808-nm laser irradiation (PTT mode), alternating magnetic field (MHT mode), and both modalities (DUAL mode). All the three methods can offer effective temperature increases (above 20 °C). DUAL-mode resulted in an approximately 2-fold increase in heating efficiency (36 °C) compared with PTT or MHT alone. For in vivo experiments, a total of 24 Lewis carcinoma-bearing mice were randomly divided into four groups: the control group (no therapy), PTT, MHT, and DUAL group. In the three therapy groups, magneto-nanomicelles were injected into the tumor and the corresponding treatment measures were performed every other day for a total of three times each. MRI scans were used to calculate tumor volume after each treatment. One-way analysis of variance (ANOVA) was employed to compare the curative effect of different treatment groups. Compared with the control group, PTT, MHT, and DUAL groups all showed a significant inhibitory effect on tumor volume (P < 0.05). In the DUAL group, the mean tumor volume was smaller than that of the PTT or the MHT group. Our work demonstrated that hyperthermia using SPIO-based magnetonanomicelles has a remarkable suppressive effect in anticancer therapy. Moreover, the combined model of hyperthermia in vivo can achieve synthetic effects with shorter healing time by using the same magneto-nanomicelles.

Hydrogel to guide chondrogenesis versus osteogenesis of mesenchymal stem cells for fabrication of cartilaginous tissues.

The ideal combination of hydrogel components for regeneration of cartilage and cartilaginous interfaces is a significant challenge because control over differentiation into multiple lineages is necessary. Stabilization of the phenotype of stem cell derived chondrocytes is needed to avoid undesired progression to terminal hypertrophy and tissue mineralization. A novel ternary blend hydrogel composed of methacrylated poly(ethylene glycol) (PEG), gelatin, and heparin (PGH) was designed to guide chondrogenesis by bone marrow derived mesenchymal stem cells (BMSCs) and maintenance of their cartilaginous phenotype. The hydrogel material effects on chondrogenic and osteogenic differentiation by BMSCs were evaluated in comparison to methacrylated gelatin hydrogel (GEL), a conventional bioink used for both chondrogenic and osteogenic applications. PGH and GEL hydrogels were loaded with goat BMSCs and cultured in chondrogenic and osteogenic mediums in vitro over six weeks. The PGH showed no sign of mineral deposition in an osteogenic environment in vitro. To further evaluate material effects, the hydrogels were loaded with adult human BMSCs (hBMSCs) and transforming growth factor ß-3 and grown in subcutaneous pockets in mice over eight weeks. Consistent with the in vitro results, the PGH had greater potential to induce chondrogenesis by BMSCs in vivo compared to the GEL as evidenced by elevated gene expression of chondrogenic markers, supporting its potential for stable cartilage engineering. The PGH also showed a greater percentage of GAG positive cells compared to the GEL. Unlike the GEL, the PGH hydrogel exhibited anti-osteogenic effects in vivo as evidenced by negative Von Kossa staining and suppressed gene expression of hypertrophic and osteogenic markers. By nature of their polymer composition alone, the PGH and GEL regulated BMSC differentiation down different osteochondral lineages. Thus, the PGH and GEL are promising hydrogels to regenerate stratified cartilaginous interfacial tissues in situ, such as the mandibular condyle surface, using undifferentiated BMSCs and a stratified scaffold design.

Effect of the Periapical "Inflammatory Plug" on Dental Pulp Regeneration: A Histologic In Vivo Study.

INTRODUCTION: In the current study, we investigate the effect of the inflammation occupying the apical foramen-a phenomenon we refer to as "inflammatory plug"-on the regenerative potential of a root canal therapy. METHODS: We performed root canal treatment (RCT) in 12 canine root canals while aseptically instrumenting the apex to a 0.5-mm-wide foramen and obturating the canals with the following materials: collagen sponge, platelet-rich fibrin, and blood clot (no material introduced). RESULTS: We were successful in maintaining the integrity of the periapical tissue in 8 of 12 RCTs. Injury to the periapical tissue occurred during the remaining 4 RCTs, which initiated inflammation accompanied by bone and dentin resorption. Our histologic analyses showed that the resulting inflammatory plug contained abundant M1 macrophages and was associated with an absence of intracanal cellular infiltration. On the contrary, noninflamed samples showed signs of repair, as indicated by the migration of periapical cells throughout the root canal. CONCLUSIONS: We conclude that controlling periapical inflammation is key while attempting to achieve dental pulp regeneration.

Identification of Withaferin A as a Potential Candidate for Anti-Cancer Therapy in Non-Small Cell Lung Cancer.

Low response rate and recurrence are common issues in lung cancer; thus, identifying a potential compound for these patients is essential. Utilizing an in silico screening method, we identified withaferin A (WA), a cell-permeable steroidal lactone initially extracted from Withania somnifera, as a potential anti-lung cancer and anti-lung cancer stem-like cell (CSC) agent. First, we demonstrated that WA exhibited potent cytotoxicity in several lung cancer cells, as evidenced by low IC50 values. WA concurrently induced autophagy and apoptosis and the activation of reactive oxygen species (ROS), which plays an upstream role in mediating WA-elicited effects. The increase in p62 indicated that WA may modulate the autophagy flux followed by apoptosis. In vivo research also demonstrated the anti-tumor effect of WA treatment. We subsequently demonstrated that WA could inhibit the growth of lung CSCs, decrease side population cells, and inhibit lung cancer spheroid-forming capacity, at least through downregulation of mTOR/STAT3 signaling. Furthermore, the combination of WA and chemotherapeutic drugs, including cisplatin and pemetrexed, exerted synergistic effects on the inhibition of epidermal growth factor receptor (EGFR) wild-type lung cancer cell viability. In addition, WA can further enhance the cytotoxic effect of cisplatin in lung CSCs. Therefore, WA alone or in combination with standard chemotherapy is a potential treatment option for EGFR wild-type lung cancer and may decrease the occurrence of cisplatin resistance by inhibiting lung CSCs.