K-Doping Suppresses Oxygen Redox in P2-Na0.67Ni0.11Cu0.22Mn0.67O2 Cathode Materials for Sodium-Ion Batteries.

In P2-type layered oxide cathodes, Na site-regulation strategies are proposed to modulate the Na+ distribution and structural stability. However, their impact on the oxygen redox reactions remains poorly understood. Herein, the incorporation of K+ in the Na layer of Na0.67Ni0.11Cu0.22Mn0.67O2 is successfully applied. The effects of partial substitution of Na+ with K+ on electrochemical properties, structural stability, and oxygen redox reactions have been extensively studied. Improved Na+ diffusion kinetics of the cathode is observed from galvanostatic intermittent titration technique (GITT) and rate performance. The valence states and local structural environment of the transition metals (TMs) are elucidated via operando synchrotron X-ray absorption spectroscopy (XAS). It is revealed that the TMO2 slabs tend to be strengthened by K-doping, which efficiently facilitates reversible local structural change. Operando X-ray diffraction (XRD) further confirms more reversible phase changes during the charge/discharge for the cathode after K-doping. Density functional theory (DFT) calculations suggest that oxygen redox reaction in Na0.62K0.03Ni0.11Cu0.22Mn0.67O2 cathode has been remarkably suppressed as the nonbonding O 2p states shift down in the energy. This is further corroborated experimentally by resonant inelastic X-ray scattering (RIXS) spectroscopy, ultimately proving the role of K+ incorporated in the Na layer.

Transcription factors MhDREB2A/MhZAT10 play a role in drought and cold stress response crosstalk in apple.

Drought and cold stresses seriously affect tree growth and fruit yield during apple (Malus domestica) production, with combined stress causing injury such as shoot shriveling. However, the molecular mechanism underlying crosstalk between responses to drought and cold stress remains to be clarified. In this study, we characterized the zinc finger transcription factor ZINC FINGER OF ARABIDOPSIS THALIANA 10 (ZAT10) through comparative analysis of shoot-shriveling tolerance between tolerant and sensitive apple rootstocks. MhZAT10 responded to both drought and cold stresses. Heterologous expression of MhZAT10 in the sensitive rootstock 'G935' from domesticated apple (Malus domestica) promoted shoot-shriveling tolerance, while silencing of MhZAT10 expression in the tolerant rootstock 'SH6' of Malus honanensis reduced stress tolerance. We determined that the apple transcription factor DEHYDRATION RESPONSE ELEMENT-BINDING PROTEIN 2A (DREB2A) is a direct regulator activating the expression of MhZAT10 in response to drought stress. Apple plants overexpressing both MhDREB2A and MhZAT10 genes exhibited enhanced tolerance to drought and cold stress, while plants overexpressing MhDREB2A but with silenced expression of MhZAT10 showed reduced tolerance, suggesting a critical role of MhDREB2A-MhZAT10 in the crosstalk between drought and cold stress responses. We further identified drought-tolerant MhWRKY31 and cold-tolerant MhMYB88 and MhMYB124 as downstream regulatory target genes of MhZAT10. Our findings reveal a MhDREB2A-MhZAT10 module involved in crosstalk between drought and cold stress responses, which may have applications in apple rootstock breeding programs aimed at developing shoot-shriveling tolerance.

Targeting the macrophage immunocheckpoint: a novel insight into solid tumor immunotherapy.

Tumor immunotherapy, which targets immune checkpoints, presents a promising strategy for the treatment of various cancer types. However, current clinical data indicate challenges in its application to solid tumors. Recent studies have revealed a significant correlation between the degree of immune response in immunotherapy and the tumor microenvironment, particularly with regard to tumor-infiltrating immune cells. Among these immune cells, macrophages, a critical component, are playing an increasingly vital role in tumor immunotherapy. This review focuses on elucidating the role of macrophages within solid tumors and provides an overview of the progress in immunotherapy approaches centered around modulating macrophage responses through various immune factors. Video Abstract.

Glial growth factor 2 treatment alleviates ischemia and reperfusion-damaged integrity of the blood-brain barrier through decreasing Mfsd2a/caveolin-1-mediated transcellular and Pdlim5/YAP/TAZ-mediated paracellular permeability.

The impairment of blood-brain barrier (BBB) integrity is the pathological basis of hemorrhage transformation and vasogenic edema following thrombolysis and endovascular therapy. There is no approved drug in the clinic to reduce BBB damage after acute ischemic stroke (AIS). Glial growth factor 2 (GGF2), a recombinant version of neuregulin-1ß that can stimulates glial cell proliferation and differentiation, has been shown to alleviate free radical release from activated microglial cells. We previously found that activated microglia and proinflammatory factors could disrupt BBB after AIS. In this study we investigated the effects of GGF2 on AIS-induced BBB damage as well as the underlying mechanisms. Mouse middle cerebral artery occlusion model was established: mice received a 90-min ischemia and 22.5 h reperfusion (I/R), and were treated with GGF2 (2.5, 12.5, 50 ng/kg, i.v.) before the reperfusion. We showed that GGF2 treatment dose-dependently decreased I/R-induced BBB damage detected by Evans blue (EB) and immunoglobulin G (IgG) leakage, and tight junction protein occludin degradation. In addition, we found that GGF2 dose-dependently reversed AIS-induced upregulation of vesicular transcytosis increase, caveolin-1 (Cav-1) as well as downregulation of major facilitator superfamily domain containing 2a (Mfsd2a). Moreover, GGF2 decreased I/R-induced upregulation of PDZ and LIM domain protein 5 (Pdlim5), an adaptor protein that played an important role in BBB damage after AIS. In addition, GGF2 significantly alleviated I/R-induced reduction of YAP and TAZ, microglial cell activation and upregulation of inflammatory factors. Together, these results demonstrate that GGF2 treatment alleviates the I/R-compromised integrity of BBB by inhibiting Mfsd2a/Cav-1-mediated transcellular permeability and Pdlim5/YAP/TAZ-mediated paracellular permeability.

Application of Perioperative Pain Management in the Perioperative Nursing of Labia Minora Plasty and its Effect on the Rehabilitation of Patients.

Objective: The objective of this study is to investigate effective pain management strategies for women undergoing labiaplasty surgery. By focusing on pain relief, patient rehabilitation, and satisfaction improvement, we aim to enhance the overall patient experience and outcomes of this common gynecological plastic surgery. Methods: A total of 126 individuals diagnosed with labia minora hypertrophy and who underwent plastic surgery on their labia minora within the period of July 2020 to July 2023 were chosen as the participants for this study. They were divided into an observation group and a comparison group, each consisting of 63 cases, based on the different nursing methods. The comparison group was treated with routine perioperative nursing after labia minora surgery, and the observation group was treated with perioperative pain nursing management based on the comparison group. Postoperative pain score, comfort score, incision healing time, first urination time, night Pittsburgh Sleep Quality Index (PSQI) score, complications, and satisfaction were compared between the two groups. All data were established in an Excel database, and statistical analysis was performed using SPSS26.0. Statistical methods used include descriptive analysis, t tests, and Chi-square tests. Results: The mean incision healing time of the observation group was 3.90±0.61 days, and that of the control group was 3.62±0.64 days. The mean incision healing time of the observation group was significantly different from that of the control group (P < .05). VRS scores and PSQI scores were significantly lower in both groups 1 week aftercare compared with 1 day before care, indicating improvements in pain and sleep quality. The improvement degree of VRS score and PSQI score in the observation group was significantly different (P < .05). The number of incision infections, hematoma, flap necrosis, skin scar, delayed healing, and total complication rate were 3 in the observation group and 11 in the comparison group, indicating that the complication rate in the observation group was significantly lower than that in the comparison group. The comparison difference was statistically significant (P < .05). Through the Chi-square test, the nursing satisfaction and perineal aesthetic effect satisfaction of the observation group were significantly higher than those of the comparison group, and the difference was statistically significant (P < .05). Conclusions: The implementation of perioperative pain nursing management has been shown to effectively alleviate pain in patients diagnosed with labia minora hypertrophy. This approach not only enhances treatment comfort but also significantly reduces the occurrence of postoperative complications. Additionally, it accelerates the healing process of incisions, improves the quality of incision healing, and enhances patient satisfaction with both the aesthetic outcome of the perineal area and the quality of nursing care provided.

Entropy-Mediated Stable Structural Evolution of Prussian White Cathodes for Long-Life Na-Ion Batteries.

The high-entropy approach is applied to monoclinic Prussian White (PW) Na-ion cathodes to address the issue of unfavorable multilevel phase transitions upon electrochemical cycling, leading to poor stability and capacity decay. A series of Mn-based samples with up to six metal species sharing the N-coordinated positions was synthesized. The material of composition Na1.65 Mn0.4 Fe0.12 Ni0.12 Cu0.12 Co0.12 Cd0.12 [Fe(CN)6 ]0.92 □0.08 ⋅ 1.09H2 O was found to exhibit superior cyclability over medium/low-entropy and conventional single-metal PWs. We also report, to our knowledge for the first time, that a high-symmetry crystal structure may be advantageous for high-entropy PWs during battery operation. Computational comparisons of the formation enthalpy demonstrate that the compositionally less complex materials are prone to phase transitions, which negatively affect cycling performance. Based on data from complementary characterization techniques, an intrinsic mechanism for the stability improvement of the disordered PW structure upon Na+ insertion/extraction is proposed, namely the dual effect of suppression of phase transitions and mitigation of gas evolution.

Optical multiple-image authentication based on computational ghost imaging and hybrid non-convex second-order total variation.

An optical security method for multiple-image authentication is proposed based on computational ghost imaging and hybrid non-convex second-order total variation. Firstly, each original image to be authenticated is encoded to the sparse information using computational ghost imaging, where illumination patterns are generated based on Hadamard matrix. In the same time, the cover image is divided into four sub-images with wavelet transform. Secondly, one of sub-images with low-frequency coefficients is decomposed using singular value decomposition (SVD), and all sparse data are embedded into the diagonal matrix with the help of binary masks. To enhance the security, the generalized Arnold transform is used to scramble the modified diagonal matrix. After using SVD again, the marked cover image carrying the information of multiple original images is obtained using the inverse wavelet transform. In the authentication process, the quality of each reconstructed image can be greatly improved based on hybrid non-convex second-order total variation. Even at a very low sampling ratio (i.e., 6%), the existence of original images can be efficiently verified using the nonlinear correlation maps. To our knowledge, it is first to embed sparse data into the high-frequency sub-image using two cascaded SVDs, which can guarantee high robustness against the Gaussian filter and sharpen filter. The optical experiments demonstrate the feasibility of the proposed mechanism, which can provide an effective alternative for the multiple-image authentication.

Multicomponent cyclization with azides to synthesize N-heterocycles.

Heterocyclic compounds, both naturally derived and synthetically produced, constitute a wide variety of biologically active and industrially important compounds. The synthesis and application of heterocyclic compounds have garnered significant attention and experienced rapid growth in recent decades. Organic azides, due to their unique properties and distinctive reactivity, have become a convenient chemical tool for achieving a wide range of heterocycles such as triazoles and tetrazoles. Importantly, the field of multicomponent reaction (MCR) chemistry provides a convergent approach to access various N-heterocyclic scaffolds, offering novelty, diversity, and complexity. However, the exploration of MCR pathways to N-heterocyclic compounds remains incomplete. Here, we review the use of multicomponent reactions for the preparation of N-heterocycles. A wide range of reactions based on azides for the synthesis of various types of N-heterocyclic systems have been developed.

Development of a General and Selective Nanostructured Cobalt Catalyst for the Hydrogenation of Benzofurans, Indoles and Benzothiophenes.

The selective hydrogenation of benzofurans in the presence of a heterogeneous non-noble metal catalyst is reported. The developed optimal catalytic material consists of cobalt-cobalt oxide core-shell nanoparticles supported on silica, which has been prepared by the immobilization and pyrolysis of cobalt-DABCO-citric acid complex on silica under argon at 800 °C. This novel catalyst allows for the selective hydrogenation of simple and functionalized benzofurans to 2,3-dihydrobenzofurans as well as related heterocycles. The versatility of the reported protocol is showcased by the reduction of selected drugs and deuteration of heterocycles. Further, the stability, recycling, and reusability of the Co-nanocatalyst are demonstrated.

Vegetable-derived indole enhances the melanoma-treating efficacy of chemotherapeutics.

Food-drug interaction is an important but overlooked issue. For example, little is known concerning whether or not the chemotherapy of cancers is affected by the well-defined dietary chemicals such as 2-(indol-3-ylmethyl)-3,3'-diindolylmethane (LTr1) derived from daily consumed cruciferous vegetables. This work, inspired by the described melanogenesis reduction by certain indoles, presents that LTr1 mitigates the melanogenesis and thus potentiates the in vitro and in vivo anti-melanoma effectiveness of different chemotherapeutic agents including dacarbazine, vemurafenib, and sorafenib. In B16 melanoma cells, LTr1 was shown to inhibit the melanogenesis by acting towards the regulatory (R) subunit of protein kinase A (PRKAR1a) associated with the phosphorylation of cAMP-response element binding protein (CREB). This allows LTr1 to reduce the expression of melanogenesis-related enzymes such as tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and tyrosinase-related protein 2 (TYRP2). Furthermore, LTr1 was addressed to bind to the aryl hydrocarbon receptor (AhR) and up-regulate the expression of CYP1A1 encoding cytochrome P450 1A1, leading to the escalation of reactive oxygen species (ROS) level. The increased ROS generation promotes the cysteine-to-cystine transformation to inhibit the pheomelanogenesis in melanomas. Collectively, the work identifies LTr1 as a new melanogenesis inhibitor that modulates the PKA/CREB/MITF and AhR/CYP1A1/ROS pathways, thereby providing a new option for (re)sensitizing melanomas to chemotherapeutics.

Three new polyketide derivatives of the endophytic fungus Aspergillus cristatus 2H1.

Three new polyketide derivatives, 2-ethoxycarbonyl-endocrocin (1), 6-methoxy-2-ethoxycarbonyl-endocrocin (2) and pannorin C (3), along with sixteen known compounds (4-19) were isolated from a plant endophytic fungus Aspergillus cristatus 2H1. Their structures were elucidated by 1D/2D NMR and HR-ESI-MS data analysis. Compound 3 showed weak antibacterial activity against Staphylococcus aureus (MIC 20 µg/ml). Compounds 14 and 15 showed effective cytotoxicity on human melanoma A375 cells (IC50 4.13 µM for 14, 3.39 µM for 15).

Synthesis and antitumor activity of benzophenone compound.

Seven benzophenone compounds were synthesized in one or two steps, then their antitumor activity was evaluated. The total yields ranged from 9% to 44%. Compounds 3c-5c exhibited obvious antitumor activity. Among them, compounds 3c and 4c exhibited excellent and broad-spectrum antitumor activity. Compound 3c exhibited much stronger inhibitory activities against fourteen cancer cells than cisplatin. In particular, compound 3c exhibited stronger cytotoxicity against hepatocarcinoma SMMC-7721 cells than Taxol, with a half maximal inhibitory concentration (IC50) of approximately 0.111 µM. These results demonstrated that compounds 3c, 4c and 5c were very promising antitumor leads for further structural modification.

Necroptosis Contributes to LPS-Induced Activation of the Hypothalamic-Pituitary-Adrenal Axis in a Piglet Model.

Stressors cause activation of the hypothalamic-pituitary-adrenal (HPA) axis and a systemic inflammatory response. As a newly proposed cell death manner in recent years, necroptosis occurs in a variety of tissue damage and inflammation. However, the role of necroptosis in HPA axis activation remains to be elucidated. The aim of this study was to investigate the occurrence of necroptosis and its role in HPA activation in a porcine stress model induced by Escherichia coli lipopolysaccharide (LPS). Several typical stress behaviors like fever, anorexia, shivering and vomiting were observed in piglets after LPS injection. HPA axis was activated as shown by increased plasma cortisol concentration and mRNA expression of pituitary corticotropin-releasing hormone receptor 1 (CRHR1) and adrenal steroidogenic acute regulatory protein (StAR). The mRNA expression of tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 in the hypothalamus, pituitary gland and adrenal gland was elevated by LPS, accompanied by the activation of necroptosis indicated by higher mRNA expression of necroptosis signals including receptor-interacting protein kinase (RIP) 1, RIP3, and phosphorylated mixed-lineage kinase domain-like protein (MLKL). Furthermore, necrostatin-1 (Nec-1), an inhibitor of necroptosis, inhibited necroptosis indicated by decreased mRNA levels of RIP1, RIP3, MLKL, and phosphoglycerate mutase family member 5 (PGAM5) in the hypothalamus, pituitary gland and adrenal gland. Nec-1 also decreased the mRNA expression of TNF-α and IL-ß and inhibited the activation of the HPA axis indicated by lower plasma cortisol concentration and mRNA expression of adrenal type 2 melanocortin receptor (MC2R) and StAR. These findings suggest that necroptosis is present and contributes to HPA axis activation induced by LPS. These findings provide a potential possibility for necroptosis as an intervention target for alleviating HPA axis activation and stress responses.

Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial.

BACKGROUND: The interleukin-23 (IL-23)/T-helper 17 cell pathway is implicated in psoriatic arthritis pathogenesis. Guselkumab, an IL-23 inhibitor that specifically binds the IL-23 p19 subunit, significantly and safely improved psoriatic arthritis in a phase 2 study. DISCOVER-2 was a phase 3 trial to assess guselkumab in biologic-naive patients with psoriatic arthritis. METHODS: This phase 3, double-blind, placebo-controlled study was done at 118 sites in 13 countries across Asia, Europe, and North America. We enrolled biologic-naive patients with active psoriatic arthritis (at least five swollen joints, at least five tender joints, and C-reactive protein ≥0·6 mg/dL) despite standard therapies. Patients were randomly assigned (1:1:1, computer-generated permuted blocks; stratified by baseline disease-modifying antirheumatic drug use and C-reactive protein concentration) to subcutaneous injections of guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0, 4, then every 8 weeks; or placebo. The primary endpoint was American College of Rheumatology 20% improvement (ACR20) response at week 24 in all patients per assigned treatment group. Safety was assessed in all patients per treatment received. This trial is registered at ClinicalTrials.gov, NCT03158285 (active, not recruiting). FINDINGS: From July 13, 2017, to Aug 3, 2018, 1153 patients were screened, of whom 741 were randomly assigned to receive guselkumab every 4 weeks (n=246), every 8 weeks (n=248), or placebo (n=247). One patient in the every 4 weeks group and one in the placebo group did not start treatment, and the remaining 739 patients started treatment; 716 patients continued treatment up to week 24. Significantly greater proportions of patients in the guselkumab every 4 weeks group (156 [64%] of 245 [95% CI 57-70]) and every 8 weeks group (159 [64%] of 248 [58-70]) than in the placebo group (81 [33%] of 246 [27-39]) achieved an ACR20 response at week 24 (percentage differences vs placebo 31% [95% CI 22-39] for the every 4 weeks group and 31% [23-40] for the every 8 weeks group; both p<0·0001). Up to week 24, serious adverse events occurred in eight (3%) of 245 patients receiving guselkumab every 4 weeks (three serious infections), three (1%) of 248 receiving guselkumab every 8 weeks (one serious infection), and seven (3%) of 246 receiving placebo (one serious infection). No deaths occurred. INTERPRETATION: Guselkumab, a human monoclonal antibody that specifically inhibits IL-23 by binding the cytokine's p19 subunit, was efficacious and demonstrated an acceptable benefit-risk profile in patients with active psoriatic arthritis who were naive to treatment with biologics. These data support the use of selective inhibition of IL-23 to treat psoriatic arthritis. FUNDING: Janssen Research and Development.

Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFα inhibitor treatment (DISCOVER-1): a double-blind, randomised, placebo-controlled phase 3 trial.

BACKGROUND: Many patients with psoriatic arthritis have an inadequate response to tumor necrosis factor (TNF) inhibitors. Guselkumab, a specific inhibitor of interleukin-23 (IL-23) via IL-23 p19 subunit binding, significantly improved psoriatic arthritis signs and symptoms with an acceptable safety profile in a phase 2 trial. METHODS: This multicentre, double-blind, randomised, placebo-controlled, phase 3 trial was done at 86 sites in 13 countries across Asia, Australasia, Europe, and North America and enrolled adults with active psoriatic arthritis (at least three swollen and three tender joints; and C-reactive protein ≥0·3 mg/dL) despite standard therapies. Eligibility criteria included inadequate response to or intolerance of standard treatment, including at least 4 months of apremilast, at least 3 months of non-biologic disease-modifying antirheumatic drugs (DMARDs), or at least 4 weeks of non-steroidal anti-inflammatory drugs for psoriatic arthritis. About 30% of study participants could have previously received one or two TNF inhibitors. Patients were randomly assigned (1:1:1, computer-generated permuted blocks; stratified by baseline DMARD and previous TNF inhibitor use) to subcutaneous guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0, 4, then every 8 weeks; or matching placebo. The primary endpoint was American College of Rheumatology 20% improvement (ACR20) at week 24 in all patients per assigned treatment group using non-responder imputation. Safety was assessed in all patients per treatment received. This trial is registered at ClinicalTrials.gov, NCT03162796 (active, not recruiting). FINDINGS: From Aug 28, 2017, to Aug 17, 2018, we screened 624 patients, of whom 381 were randomly assigned and treated with guselkumab every 4 weeks (n=128), guselkumab every 8 weeks (n=127), or placebo (n=126). 362 patients continued study treatment up to week 24. The primary endpoint was met: ACR20 at week 24 was achieved by significantly greater proportions of patients in the guselkumab every 4 weeks group (76 [59%] of 128 [95% CI 50-68]) and every 8 weeks group (66 [52%] of 127 [43-61]) than in the placebo group (28 [22%] of 126 [15-30]), with percentage differences versus placebo of 37% (95% CI 26-48) for the every 4 weeks group and 30% (19-41) for the every 8 weeks group (both p<0·0001). Serious adverse events up to week 24 occurred in no patients receiving guselkumab every 4 weeks, four (3%) patients receiving guselkumab every 8 weeks, and five (4%) patients receiving placebo. Up to week 24, one patient in the placebo group died from cardiac failure and two had serious infections; no guselkumab-treated patient died or had serious infections. INTERPRETATION: Guselkumab demonstrated a favourable benefit-risk profile and might be an effective treatment option for patients with active psoriatic arthritis. FUNDING: Janssen Research and Development.

Pathogenic Escherichia coli-Specific Bacteriophages and Polyvalent Bacteriophages in Piglet Guts with Increasing Coliphage Numbers after Weaning.

Postweaning diarrhea in pigs is mainly caused by pathogenic Escherichia coli and is a major source of revenue loss to the livestock industry. Bacteriophages dominate the gut virome and have the potential to regulate bacterial communities and thus influence the intestinal physiology. To determine the biological characterization of intestinal coliphages, we isolated and identified the fecal coliphages of healthy preweaned and postweaned piglets from the Nanjing and Chuzhou pig farms. First, ahead of coliphage isolation, 87 E. coli strains were isolated from healthy or diarrheal fecal samples from three pig farms, of which 8 were pathogenic strains, including enterotoxigenic E. coli (ETEC) and enteropathogenic E. coli (EPEC). Of the E. coli strains, 87.3% possessed drug resistance to three antibiotics. Using these 87 E. coli strains as indicator hosts, we isolated 45 coliphages and found a higher abundance in the postweaning stage than in the preweaning stage (24 versus 17 in the Nanjing and 13 versus 4 in the Chuzhou farm). Furthermore, each farm had a single most-prevalent coliphage strain. Pathogenic E. coli-specific bacteriophages were commonly detected (9/10 samples in the Nanjing farm and 7/10 in the Chuzhou farm) in guts of sampled piglets, and most had significant bacteriostatic effects (P < 0.05) on pathogenic E. coli strains. Three polyvalent bacteriophages (N24, N30, and C5) were identified. The N30 and C5 strains showed a genetic identity of 89.67%, with mild differences in infection characteristics. Our findings suggest that pathogenic E. coli-specific bacteriophages as well as polyvalent bacteriophages are commonly present in piglet guts and that weaning is an important event that affects coliphage numbers. IMPORTANCE Previous studies based on metagenomic sequencing reported that gut bacteriophages profoundly influence gut physiology but did not provide information regarding the host range and biological significance. Here, we screened coliphages from the guts of preweaned and postweaned piglets against indicator hosts, which allowed us to identify the pathogenic E. coli-specific bacteriophages and polyvalent bacteriophages in pig farms and quantify their abundance. Our approach complements sequencing methods and provides new insights into the biological characterizations of bacteriophage in the gut along with the ecological effects of intestinal bacteriophages.

Resolution of enthesitis by guselkumab and relationships to disease burden: 1-year results of two phase 3 psoriatic arthritis studies.

OBJECTIVE: To further characterize the effect of guselkumab, a selective IL-23p19-subunit inhibitor approved for PsA, on enthesitis and assess relationships between enthesitis resolution and patient status/outcomes. METHODS: Adults with active PsA despite standard therapies in the phase 3 DISCOVER-1 and DISCOVER-2 studies were randomized 1:1:1 to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at week 0, week 4, Q8W; or placebo through week 20 followed by guselkumab 100 mg Q4W. Independent assessors evaluated enthesitis using the Leeds Enthesitis Index (LEI; total score 0-6). Enthesitis findings through week 24 were pre-specified to be pooled across studies; post hoc and week 52 analyses also employed pooled data. RESULTS: Among 1118 randomized, treated patients in DISCOVER-1 and 2 who had ≥1 LEI site evaluated, 65% had enthesitis at baseline. These patients exhibited numerically more swollen and tender joints, systemic inflammation and impaired physical function than patients without enthesitis. Guselkumab Q4W and Q8W were superior to placebo in resolving pre-existing enthesitis at week 24 (45 and 50% vs 29%; both adjusted P = 0.0301). Enthesitis resolution rates continued to rise; 58% of guselkumab-randomized patients achieved resolution at week 52, including patients with mild (LEI = 1; 70-75%), moderate (LEI = 2; 69-73%) or severe (LEI = 3-6; 42-44%) enthesitis at baseline. Among guselkumab-randomized patients with resolved enthesitis at week 24, 42% achieved minimal disease activity at week 52, vs 17% of patients with unresolved enthesitis. CONCLUSION: Guselkumab resulted in higher proportions of PsA patients with resolved enthesitis by week 24, with maintenance of resolution rates through 1 year. As enthesitis confers greater disease burden, sustained resolution could portend better patient outcomes. CLINICAL TRIAL REGISTRATION: DISCOVER 1 (NCT03162796) and DISCOVER 2 (NCT03158285).

Manipulation of Organic Afterglow by Thermodynamic and Kinetic Control.

The fabrication of room-temperature organic phosphorescence and afterglow materials, as well as the transformation of their photophysical properties, has emerged as an important topic in the research field of luminescent materials. Here, we report the establishment of energy landscapes in dopant-matrix organic afterglow systems where the aggregation states of luminescent dopants can be controlled by doping concentrations in the matrices and the methods of preparing the materials. Through manipulation by thermodynamic and kinetic control, dopant-matrix afterglow materials with different aggregation states and diverse afterglow properties can be obtained. The conversion from metastable aggregation state to thermodynamic stable aggregation state of the dopant-matrix afterglow materials to leads to the emergence of intriguing afterglow transformation behavior triggered by thermal and solvent annealing. The thermodynamically unfavorable reversible afterglow transformation process can also be achieved by coupling the dopant-matrix afterglow system to mechanical forces.

Signal Enhancement of Pressure-Sensitive Film Based on Localized Surface Plasmon Resonance.

Pressure-sensitive films have been used for measurement in micro flow, but thin films have very limited intensity, resulting in poor signal-noise ratio (SNR). This paper presents a pressure-sensitive film whose emission signal is enhanced by silver nanoparticles (AgNPs) based on localized surface plasmon resonance (LSPR). Electronic beam evaporator and annealing furnace are used to fabricate silver nanotexture surface. PtTFPP and polystyrene are dissolved in toluene and then spin-coated on the silver nanotexture surface to prepare the pressure-sensitive films. Signal enhancement of film with AgNPs due to LSPR is analyzed and enhancement effect of samples with different particle sizes and spacer thickness are compared. Pressure and temperature calibrations are performed to assess the sensing performance of pressure-sensitive films. Pressure-sensitive films with AgNPs demonstrate signal enhancement due to LSPR and show promise for measurement in micro flow.

Efficient synthesis, and antitumor and antioxidant activities of polyhydroxybenzophenone.

Five polyhydroxybenzophenones were synthesized, then their antitumor and antioxidant activities were evaluated. Compounds 1-3 and 5 exhibited obvious antitumor activity. Among them, compounds 1 and 2 exhibited stronger cytotoxicity against hepatocarcinoma SMMC-7721 cells than cisplatin, with half maximal inhibitory concentrations (IC50) of approximately 3.86 and 5.32 µM, respectively. Compounds 1, 2, and 3 exhibited stronger antioxidant activity than trolox, with IC50 values of 11.15, 10.15, and 8.91 µM, respectively, and the antioxidant mechanism and strength of all compounds were further verified using computational chemistry. These results demonstrated that compounds 1-3 and 5 were very promising leads for further structural modification.