Chitinase 3-like-1 Inhibits Innate Antitumor and Tissue Remodeling Immune Responses by Regulating CD47-SIRPα- and CD24-Siglec10-Mediated Phagocytosis.

Innate immune responses such as phagocytosis are critically linked to the generation of adaptive immune responses against the neoantigens in cancer and the efferocytosis that is essential for homeostasis in diseases characterized by lung injury, inflammation, and remodeling as in chronic obstructive pulmonary disease (COPD). Chitinase 3-like-1 (CHI3L1) is induced in many cancers where it inhibits adaptive immune responses by stimulating immune checkpoint molecules (ICPs) and portends a poor prognosis. CHI3L1 is also induced in COPD where it regulates epithelial cell death. In this study, we demonstrate that pulmonary melanoma metastasis inhibits macrophage phagocytosis by stimulating the CD47-SIRPα and CD24-Siglec10 phagocytosis checkpoint pathways while inhibiting macrophage "eat me" signals from calreticulin and HMGB1. We also demonstrate that these effects on macrophage phagocytosis are associated with CHI3L1 stimulation of the SHP-1 and SHP-2 phosphatases and inhibition of the accumulation and phosphorylation of cytoskeleton-regulating nonmuscle myosin IIa. This inhibition of innate immune responses such as phagocytosis provides a mechanistic explanation for the ability of CHI3L1 to stimulate ICPs and inhibit adaptive immune responses in cancer and diseases such as COPD. The ability of CHI3L1 to simultaneously inhibit innate immune responses, stimulate ICPs, inhibit T cell costimulation, and regulate a number of other oncogenic and inflammation pathways suggests that CHI3L1-targeted therapeutics are promising interventions in cancer, COPD, and other disorders.

Spin wavepackets in the Kagome ferromagnet Fe3Sn2: Propagation and precursors.

The propagation of spin waves in magnetically ordered systems has emerged as a potential means to shuttle quantum information over large distances. Conventionally, the arrival time of a spin wavepacket at a distance, d, is assumed to be determined by its group velocity, vg. Here, we report time-resolved optical measurements of wavepacket propagation in the Kagome ferromagnet Fe3Sn2 that demonstrate the arrival of spin information at times significantly less than d/vg. We show that this spin wave "precursor" originates from the interaction of light with the unusual spectrum of magnetostatic modes in Fe3Sn2. Related effects may have far-reaching consequences toward realizing long-range, ultrafast spin wave transport in both ferromagnetic and antiferromagnetic systems.

The spontaneous symmetry breaking in Ta2NiSe5 is structural in nature.

The excitonic insulator is an electronically driven phase of matter that emerges upon the spontaneous formation and Bose condensation of excitons. Detecting this exotic order in candidate materials is a subject of paramount importance, as the size of the excitonic gap in the band structure establishes the potential of this collective state for superfluid energy transport. However, the identification of this phase in real solids is hindered by the coexistence of a structural order parameter with the same symmetry as the excitonic order. Only a few materials are currently believed to host a dominant excitonic phase, Ta2NiSe5 being the most promising. Here, we test this scenario by using an ultrashort laser pulse to quench the broken-symmetry phase of this transition metal chalcogenide. Tracking the dynamics of the material's electronic and crystal structure after light excitation reveals spectroscopic fingerprints that are compatible only with a primary order parameter of phononic nature. We rationalize our findings through state-of-the-art calculations, confirming that the structural order accounts for most of the gap opening. Our results suggest that the spontaneous symmetry breaking in Ta2NiSe5 is mostly of structural character, hampering the possibility to realize quasi-dissipationless energy transport.

Cavity-Enhanced Emission from a Silicon T Center.

Silicon T centers present the promising possibility of generating optically active spin qubits in an all-silicon device. However, these color centers exhibit long excited state lifetimes and a low Debye-Waller factor, making them dim emitters with low efficiency into the zero-phonon line. Nanophotonic cavities can solve this problem by enhancing radiative emission into the zero-phonon line through the Purcell effect. In this work, we demonstrate cavity-enhanced emission from a single T center in a nanophotonic cavity. We achieve a 2 order of magnitude increase in the brightness of the zero-phonon line relative to waveguide-coupled emitters, a 23% collection efficiency from emitter to fiber, and an overall emission efficiency into the zero-phonon line of 63.4%. We also observe a lifetime enhancement of 5, corresponding to a Purcell factor exceeding 18 when correcting for the emission to the phonon sideband. These results pave the way toward efficient spin-photon interfaces in silicon photonics.

III-nitride m-plane violet narrow ridge edge-emitting laser diodes with sidewall passivation using atomic layer deposition.

A novel deep-ridge laser structure with atomic-layer deposition (ALD) sidewall passivation was proposed that enhances the optical characteristics of 8-µm ridge width III-nitride violet lasers on freestanding m-plane GaN substrates. The internal loss was determined using the variable stripe length method, where the laser structure with ALD sidewall passivation showed lower internal loss compared to the conventional shallow-ridge laser design. ALD sidewall passivation plays a critical role in device improvements; compared to the lasers without ALD sidewall passivation, the lasers with ALD sidewall passivation yield improved optoelectrical performance and longer lifetime under continuous-wave operation at high current density. This work demonstrates the importance of ALD sidewall passivation to laser performance, which enables high energy efficiency.

SNP-based QTL mapping and identification of panicle structure-related genes in rice.

Rice is a staple crop providing a significant portion of the global food supply. It is then crucial to develop strategies for breeding high-yield cultivars to meet global food security challenges, including the UN's zero-hunger goal. In this study, QTL mapping was employed to pinpoint key genomic regions linked to traits influencing rice yield, with a focus on panicle structure-a critical determinant of grain number. Over two consecutive years, QTLs were identified using 88 JJ625LG/Namchan Recombinant Inbred Lines (JNRILs), revealing several candidate genes. Notably, Gn1a, a known regulator of grain number, was mapped within qNS1 and qNSSr1-1, while the sd1 gene, linked to plant height, was detected across multiple QTLs. Furthermore, a novel gene, OsNSMq3 (Os03g0843800), encoding a methyltransferase, was identified in various QTLs, with haplotype and sequence homology analysis suggesting its role in enhancing yield by influencing panicle structure development. The increase in primary and secondary branches, driven by these genes, leads to a higher number of spikelets per panicle, thereby boosting yield. These findings underscore the potential of candidate genes from stable QTLs as valuable tools in molecular breeding to develop high-yield rice cultivars, addressing global hunger and aiding food supply in refugee crises.

Morbidity and quality of life of totally laparoscopic versus laparoscopy-assisted distal gastrectomy for early gastric cancer: a multi-center prospective randomized controlled trial (CKLASS01).

BACKGROUND: There is a paucity of confirmatory randomized controlled trials (RCTs) comparing the effectiveness of totally laparoscopic distal gastrectomy (TLDG) vs laparoscopy-assisted distal gastrectomy (LADG) for early gastric cancer (EGC). METHODS: A phase III, prospective, multi-center RCT was conducted, wherein patients (n = 442) with clinical stage I gastric cancer eligible for laparoscopic distal gastrectomy were randomized 1:1 to the TLDG or the LADG group. Postoperative morbidity and quality of life (QoL) were compared. RESULTS: In total, 422 patients were assessed (TLDG, 216; LADG, 206) in the modified intention-to-treat (mITT) analysis. The morbidity rate did not differ significantly between the two groups (TLDG, 6.0%; LADG, 5.8%; P = 0.93). The 90-day mortality rate was comparable between the groups (TLDG, 0.5%; LADG, 0.0%; P > 0.99). TLDG was significantly associated with a lower pain score compared with LADG in patients with a BMI of ≥ 25 kg/m2 (P = 0.002) at 24 h postoperatively. Moreover, TLDG significantly improved QoL in terms of C30 social functioning at 3 and 6 months (P = 0.03 and P = 0.04), C30 global health status at 3 months (P = 0.02), and STO22 body image at 3 months (P = 0.01), with differences dissipating at 12 months. CONCLUSIONS: TLDG is not superior to LADG in terms of postoperative morbidity and mortality, but it provides better C30 social functioning at 3 and 6 months, C30 global health status and STO22 body image at 3 months, and reduces early postoperative pain for patients with a BMI of ≥ 25 kg/m2. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03393182.

Fucoidan-coated cotton dressing functionalized with biomolecules capped silver nanoparticles (LB-Ag NPs-FN-OCG) for rapid healing therapy of infected wounds.

The colonization of pathogenic microbes poses a significant clinical barrier that hinders the physiological wound-healing process. Addressing this challenge, we developed a novel wound dressing using a modified cotton gauze dressing coated with fucoidan and functionalized with silver nanoparticles (LB-Ag NPs-FN-OCG) for the rapid treatment of infected wounds. Firstly, phytochemical-capped LB-Ag NPs were synthesized and characterized using high performance liquid chromatography (HPLC), transmission electron microscopy (TEM), and zeta potential analysis. Secondly, different concentrations of LB-Ag NPs (0.1%-1%) were functionalized into FN-OCG to identify appropriate concentrations that were non-toxic with superior antibacterial activities. Screening assays, including antibacterial, hemolysis, chick chorioallantoic membrane (CAM) assay, and cytotoxicity assay, revealed that LB-Ag NPs (0.5%)-FN-OCG were non-toxic and demonstrated greater efficiency in inhibiting bacterial pathogens (Escherichia coli, Salmonella enterica, Staphylococcus aureus, and Listeria monocytogenes) and promoting fibroblast cell (NIH3T3) migration. In vivo assays revealed that LB-Ag NPs (0.5%)-FN-OCG treatment exhibited excellent wound healing activity (99.73 ± 0.01%) compared to other treatments by inhibiting bacterial colonization, maintaining the blood parameters, developing granulation tissue, new blood vessels, and collagen deposition. Overall, this study highlights that LB-Ag NPs (0.5%)-FN-OCG serve as a antibacterial wound dressing for infected wound healing applications.

Establishment of canine mammary gland tumor cell lines harboring PI3K/Akt activation as a therapeutic target.

Canine mammary gland tumors (MGT) have a poor prognosis in intact female canines, posing a clinical challenge. This study aimed to establish novel canine mammary cancer cell lines from primary tumors and characterize their cellular and molecular features to find potential therapeutic drugs. The MGT cell lines demonstrated rapid cell proliferation and colony formation in an anchorage-independent manner. Vimentin and α-SMA levels were significantly elevated in MGT cell lines compared to normal canine kidney (MDCK) cells, while CDH1 expression was either significantly lower or not detected at all, based on quantitative real-time PCR (qRT-PCR) analysis. Functional annotation and enrichment analysis revealed that epithelial-mesenchymal transition (EMT) phenotypes and tumor-associated pathways, particularly the PI3K/Akt signaling pathway, were upregulated in MGT cells. BYL719 (Alpelisib), a PI3K inhibitor, was also examined for cytotoxicity on the MGT cell lines. The results show that BYL719 can significantly inhibit the proliferation of MGT cell lines in vitro. Overall, our findings suggest that the MGT cell lines may be valuable for future studies on the development, progression, metastasis, and management of tumors.

AAV-mediated skeletal muscle specific irisin expression does not contribute to weight loss in mice.

Obesity, a chronic disease, significantly increases the risk of various diseases, including diabetes, cardiovascular diseases, and cancers. Exercise is crucial for weight management not only through energy expenditure by muscle activity but also through stimulating the secretion of myokines, which affect various tissues. Irisin, derived from the proteolytic processing of fibronectin type III domain-containing protein 5 (Fndc5), is a well-studied myokine with beneficial effects on metabolism. This study explored the feasibility of adeno-associated virus (AAV)-mediated Fndc5 gene therapy to treat obesity in a mouse model using the AAV-DIO system to express Fndc5 specifically in skeletal muscle, and investigated its anti-obesity effect. Although Fndc5 was specifically expressed in the muscle, no significant impact on body weight under normal chow or high-fat diets was observed, and no change in thermogenic gene expression in inguinal white adipose tissue was detected. Notably, Fndc5 transduction did affect bone metabolism, consistent with previous reports. These findings suggest that AAV-mediated Fndc5 gene therapy may not be an efficient strategy for obesity, contrary to our expectations. Further research is needed to elucidate the complex mechanisms involved in irisin's role in obesity and related disorders.

Hybrid Si-GaAs photonic crystal cavity for lasing and bistability.

The heterogeneous integration of silicon with III-V materials provides a way to overcome silicon's limited optical properties toward a broad range of photonic applications. Hybrid modes are a promising way to integrate such heterogeneous Si/III-V devices, but it remains unclear how to utilize these modes to achieve photonic crystal cavities. Herein, using 3D finite-difference time-domain simulations, we propose a hybrid Si-GaAs photonic crystal cavity design that operates at telecom wavelengths and can be fabricated without requiring careful alignment. The hybrid cavity consists of a patterned silicon waveguide that is coupled to a wider GaAs slab featuring InAs quantum dots. We show that by changing the width of the silicon cavity waveguide, we can engineer the hybrid modes and control the degree of coupling to the active material in the GaAs slab. This provides the ability to tune the cavity quality factor while balancing the device's optical gain and nonlinearity. With this design, we demonstrate cavity mode confinement in the GaAs slab without directly patterning it, enabling strong interaction with the embedded quantum dots for applications such as low-power-threshold lasing and optical bistability (156 nW and 18.1 µW, respectively). This heterogeneous integration of an active III-V material with silicon via a hybrid cavity design suggests a promising approach for achieving on-chip light generation and low-power nonlinear platforms.

Effects of Training with a Powered Exoskeleton on Cortical Activity Modulation in Hemiparetic Chronic Stroke Patients: A Randomized Controlled Pilot Trial.

OBJECTIVES: To investigate the effects of exoskeleton-assisted gait training in stroke patients. DESIGN: Prospective randomized controlled trial. SETTING: Rehabilitation department in a single tertiary hospital. PARTICIPANTS: Thirty (N=30) chronic stroke patients with Functional Ambulatory Category scale (FAC) between 2 and 4. INTERVENTION: Patients were randomly assigned to 1 of 2 groups: training with Healbot G, a wearable powered exoskeleton (Healbot G group; n=15), or treadmill training (control group; n=15). All participants received 30 minutes of training, 10 times per week, for 4 weeks. OUTCOME MEASUREMENTS: The primary outcome was oxyhemoglobin level changes, representing cortical activity in both motor cortices using functional near-infrared spectroscopy. The secondary outcomes included FAC, Berg Balance Scale, Motricity Index for the lower extremities (MI-Lower), 10-meter walk test, and gait symmetry ratio (spatial step and temporal symmetry ratio). RESULTS: Compared to the control group, during the entire training session, the pre-training and post-training mean cortical activity, and the amount of increment between pre- and post-training were significantly higher in the Healbot G group (∆mean ± SD; pre-training, 0.245±0.119, post-training, 0.697±0.429, between pre- and post-training, 0.471±0.401µmol, P<.001). There was no significant difference in cortical activity between affected- and unaffected hemispheres after Healbot G training. FAC (∆mean ± SD; 0.35 ± 0.50, P=.012), MI-Lower (∆mean ± SD; 7.01 ± 0.14, P=.001), and spatial step gait symmetry ratio (∆mean ± SD; -0.32 ± 0.25, P=.049) were improved significantly in the Healbot G group. CONCLUSION: Exoskeleton-assisted gait training induces cortical modulation effect in both motor cortices, a balanced cortical activation pattern with improvements in spatial step symmetry ratio, walking ability, and voluntary strength.

1-Methoxyerythrabyssin II Induces Autophagy in Leukemia Cells via PI3K/Akt/mTOR Pathways.

Leukemia, despite currently being one of the most lethal cancers worldwide, still lacks a focused treatment. The purpose of the present investigation was to evaluate the pharmacological effect of 1-methoxyerythrabyssin II, a pterocarpan identified in the roots of Lespedeza bicolor, on leukemic cells and to explore its underlying mechanism using a network pharmacology strategy. 1-Methoxyerythrabyssin II showed an antiproliferative effect in a concentration-dependent manner and exhibited a higher potency in human acute leukemia T cells (Jurkat). The G1 phase arrest induced by 1-methoxyerythrabyssin II was confirmed using a cell cycle assay, and the downregulation of CDK2 and cyclin D1 was observed using an immunoblot assay. Moreover, 1-methoxyerythrabyssin II-treated cells exhibited higher expression levels of LC3B, Atg-7, and Beclin 1 in addition to an enhanced fluorescence intensity in monodansylcadaverine staining, indicating autophagy induction by 1-methoxyerythrabyssin II. Furthermore, network pharmacology and molecular docking analyses revealed that the PI3K/Akt/mTOR pathway is a potential target of 1-methoxyerythrabyssin II in leukemic cells. In vitro assays further demonstrated that 1-methoxyerythrabyssin II promoted autophagy and suppressed cell proliferation by inhibiting the PI3K/Akt/mTOR pathway in leukemic cells. This discovery will contribute to the development of novel therapeutics and prophylactics against leukemia.

Cold-induced adaptive thermogenesis is impaired by exposure of Asian sand dust in mice.

Desertification and desert sandstorms caused by the worsening global warming pose increasing risks to human health. In particular, Asian sand dust (ASD) exposure has been related to an increase in mortality and hospital admissions for respiratory diseases. In this study, we investigated the effects of ASD on metabolic tissues in comparison to diesel particulate matter (DPM) that is known to cause adverse health effects. We found that larger lipid droplets were accumulated in the brown adipose tissues (BAT) of ASD-administered but not DPM-administered mice. Thermogenic gene expression was decreased in these mice as well. When ASD-administered mice were exposed to the cold, they failed to maintain their body temperature, suggesting that the ASD administration had led to impairments in cold-induced adaptive thermogenesis. However, impaired thermogenesis was not observed in DPM-administered mice. Furthermore, mice fed a high-fat diet that were chronically administered ASD demonstrated unexplained weight loss, indicating that chronic administration of ASD could be lethal in obese mice. We further identified that ASD-induced lung inflammation was not exacerbated in uncoupling protein 1 knockout mice, whose thermogenic capacity is impaired. Collectively, ASD exposure can impair cold-induced adaptive thermogenic responses in mice and increase the risk of mortality in obese mice.

Derrone Targeting the TGF Type 1 Receptor Kinase Improves Bleomycin-Mediated Pulmonary Fibrosis through Inhibition of Smad Signaling Pathway.

Transforming growth factor-ß (TGF-ß) has a strong impact on the pathogenesis of pulmonary fibrosis. Therefore, in this study, we investigated whether derrone promotes anti-fibrotic effects on TGF-ß1-stimulated MRC-5 lung fibroblast cells and bleomycin-induced lung fibrosis. Long-term treatment with high concentrations of derrone increased the cytotoxicity of MRC-5 cells; however, substantial cell death was not observed at low concentrations of derrone (below 0.05 µg/mL) during a three-day treatment. In addition, derrone significantly decreased the expressions of TGF-ß1, fibronectin, elastin, and collagen1α1, and these decreases were accompanied by downregulation of α-SMA expression in TGF-ß1-stimulated MRC-5 cells. Severe fibrotic histopathological changes in infiltration, alveolar congestion, and alveolar wall thickness were observed in bleomycin-treated mice; however, derrone supplementation significantly reduced these histological deformations. In addition, intratracheal administration of bleomycin resulted in lung collagen accumulation and high expression of α-SMA and fibrotic genes-including TGF-ß1, fibronectin, elastin, and collagen1α1-in the lungs. However, fibrotic severity in intranasal derrone-administrated mice was significantly less than that of bleomycin-administered mice. Molecular docking predicted that derrone potently fits into the ATP-binding pocket of the TGF-ß receptor type 1 kinase domain with stronger binding scores than ATP. Additionally, derrone inhibited TGF-ß1-induced phosphorylation and nuclear translocations of Smad2/3. Overall, derrone significantly attenuated TGF-ß1-stimulated lung inflammation in vitro and bleomycin-induced lung fibrosis in a murine model, indicating that derrone may be a promising candidate for preventing pulmonary fibrosis.

Long-term inhibition of chlortetracycline antibiotics on anaerobic digestion of swine manure.

This study aimed to identify whether chronic effects are present in the anaerobic digestion (AD) of swine manure (SM) containing chlortetracycline (CTC), which is one of the major broad-spectrum veterinary antibiotics, and to elucidate the long-term inhibitory effects and recovery from the inhibition based on AD performance and microbial community. Two continuous-stirred tank reactors treating SM with and without CTC spiking (3 mg/L) were operated for 900 days. Due to the degradation and transformation, the total concentration including CTC's epimer and isomer in the test reactor was 1.5 mg/L. The exposure level was determined according to probabilistically estimated concentrations with uncertainties in field conditions. Until the cessation of CTC exposure on day 585, the methane generation of test reactor continuously decreased to 55 ± 17 mL/g-VS/day, 53% that of control. The methane generation and organic removal were not recovered within 300 days after the CTC exposure was stopped. During the experiment, stability parameters such as pH, total ammonium nitrogen, the composition of methane and alkalinity were the same for both reactors. The concentration and composition of VFAs in the test reactor were different with those of control but not in inhibition level. Microbial profiles revealed that reduction in bacterial diversity and changed balance in microbial species resulted in the performance downgrade under the long-term antibiotic pressure. Since it is hard to recover from the inhibition and difficult to predict the inhibition using physicochemical indicators, continuous exposure to CTC needs to be avoided for the sustainable management of AD plants treating SM.

Immunohistochemical analysis of extracellular signal-regulated kinase expression in mature and immature bulls' testes and epididymides.

Extracellular signal-regulated kinase (ERK) has been implicated in mammalian testicular and epididymal development. This study aimed to investigate ERK expression in the immature and mature testes and epididymides of bulls. We evaluated ERK expression using immunoblot analysis and immunohistochemistry. Immunoblot analysis revealed that immature bull testes and epididymides had higher phosphorylated ERK (pERK) expression than mature bull testes and epididymides. pERK immunoreactivity was higher in immature epididymides than in immature testes. pERK was localised mostly in spermatogonia, undifferentiated sustentacular (Sertoli) cells, and interstitial (Leydig) cells in immature testes, as well as in some spermatocytes and spermatids in mature testes. In immature epididymides, the body and tail had higher pERK expression than the head, whereas pERK was broadly distributed throughout the stereocilia, basal cells, and connective tissues. pERK distribution in the head of mature epididymides was similar to that in immature epididymides, whereas few connective tissue cells were expressed in the body and tail of mature epididymides. Collectively, these results suggest that ERK is expressed in the testis and epididymis of immature and mature bulls with varying intensities, and the role of ERK in male reproductive organs may include the specific function of its development.

Comparison of mesophilic and thermophilic anaerobic digestions of thermal hydrolysis pretreated swine manure: Process performance, microbial communities and energy balance.

Anaerobic digestion (AD) of swine manure (SM) commonly shows low biogas output and unsatisfactory economic performance. In this study, thermophilic AD (TAD, 50 ± 1 °C) was combined with thermal hydrolysis pretreatment (THP, 170 °C/10 bar), to investigate its potential for maximizing biogas yield, securing successful digestion and microbial diversity, as well as improving energy balance. Four lab-scale continuously stirred tank reactors were operated for 300 days and compared with each other, i.e., reactor 1 (raw SM fed in mesophilic AD: RSM-MAD), reactor 2 (THP-treated SM fed in MAD: TSM-MAD), reactor 3 (RSM-TAD), and reactor 4 (TSM-TAD). The results showed that THP was efficient to increase methane production of SM, TSM-TAD mode led to the highest methane yield (129.8 ± 40.5 mL-CH4/g-VS/day) among the tests (p < 0.05). Although TAD was more likely to induce free ammonia (> 700 mg/L) or volatile fatty acids (> 6000 mg/L) accumulation compared with MAD in start-up phase, TSM-TAD treatment mode behaved a sustainable digestion process in a long-term operation. For TSM-TAD scenario, higher Shannon-Weaver (3.873) and lower Simpson index (0.061) indicated this mode ensured and enlarged the diversity of bacteria communities. Phylum Bathyarchaeota was dominant (59.3%-90.0%) in archaea community, followed by Euryarchaeota in the four reactors. RSM-MAD treatment mode achieved the highest energy output (4.65 GJ/day), TSM-TAD was less effective (-17.38 GJ/day) due to increased energy demands. Thus improving the energetic efficiency of THP units is recommended for the development of TSM-TAD treatment mode.

Kasugamycin Is a Novel Chitinase 1 Inhibitor with Strong Antifibrotic Effects on Pulmonary Fibrosis.

Pulmonary fibrosis is a devastating lung disease with few therapeutic options. CHIT1 (chitinase 1), an 18 glycosyl hydrolase family member, contributes to the pathogenesis of pulmonary fibrosis through the regulation of TGF-ß (transforming growth factor-ß) signaling and effector function. Therefore, CHIT1 is a potential therapeutic target for pulmonary fibrosis. This study aimed to identify and characterize a druggable CHIT1 inhibitor with strong antifibrotic activity and minimal toxicity for therapeutic application to pulmonary fibrosis. Extensive screening of small molecule libraries identified the aminoglycoside antibiotic kasugamycin (KSM) as a potent CHIT1 inhibitor. Elevated concentrations of CHIT1 were detected in the lungs of patients with pulmonary fibrosis. In in vivo bleomycin- and TGF-ß-stimulated murine models of pulmonary fibrosis, KSM showed impressive antifibrotic effects in both preventive and therapeutic conditions. In vitro studies also demonstrated that KSM inhibits fibrotic macrophage activation, fibroblast proliferation, and myofibroblast transformation. Null mutation of TGFBRAP1 (TGF-ß-associated protein 1), a recently identified CHIT1 interacting signaling molecule, phenocopied antifibrotic effects of KSM in in vivo lungs and in vitro fibroblasts responses. KSM inhibits the physical association between CHIT1 and TGFBRAP1, suggesting that the antifibrotic effect of KSM is mediated through regulation of TGFBRAP1, at least in part. These studies demonstrate that KSM is a novel CHIT1 inhibitor with a strong antifibrotic effect that can be further developed as an effective and safe therapeutic drug for pulmonary fibrosis.

Charge transfer dynamics and interlayer exciton formation in MoS2/VOPc mixed dimensional heterojunction.

Mixed-dimensional van der Waals heterojunctions involve interfacing materials with different dimensionalities, such as a 2D transition metal dichalcogenide and a 0D organic semiconductor. These heterojunctions have shown unique interfacial properties not found in either individual component. Here, we use femtosecond transient absorption to reveal photoinduced charge transfer and interlayer exciton formation in a mixed-dimensional type-II heterojunction between monolayer MoS2 and vanadyl phthalocyanine (VOPc). Selective excitation of the MoS2 exciton leads to hole transfer from the MoS2 valence band to VOPc highest occupied molecular orbit in ∼710 fs. On the contrary, selective photoexcitation of the VOPc layer leads to instantaneous electron transfer from its excited state to the conduction band of MoS2 in less than 100 fs. This light-initiated ultrafast separation of electrons and holes across the heterojunction interface leads to the formation of an interlayer exciton. These interlayer excitons formed across the interface lead to longer-lived charge-separated states of up to 2.5 ns, longer than in each individual layer of this heterojunction. Thus, the longer charge-separated state along with ultrafast charge transfer times provide promising results for photovoltaic and optoelectronic device applications.