Charge Trapping and Defect Dynamics as Origin of Memory Effects in Metal Halide Perovskite Memlumors.

Large language models for artificial intelligence applications require energy-efficient computing. Neuromorphic photonics has the potential to reach significantly lower energy consumption in comparison with classical electronics. A recently proposed memlumor device uses photoluminescence output that carries information about its excitation history via the excited state dynamics of the material. Solution-processed metal halide perovskites can be used as efficient memlumors. We show that trapping of photogenerated charge carriers modulated by photoinduced dynamics of the trapping states themselves explains the memory response of perovskite memlumors on time scales from nanoseconds to minutes. The memlumor concept shifts the paradigm of the detrimental role of charge traps and their dynamics in metal halide perovskite semiconductors by enabling new applications based on these trap states. The appropriate control of defect dynamics in perovskites allows these materials to enter the field of energy-efficient photonic neuromorphic computing, which we illustrate by proposing several possible realizations of such systems.

[Clinical study of ear keloids with surgical excision and intraoperative low-energy X-ray irradiation therapy].

Objective:To explore the clinical efficacy of surgical excision combined with low-energy X-ray irradiation in the treatment of ear keloids. Methods:Clinical data of 32 cases of ear keloid lesions that received surgical treatment alone or surgery combined with radiotherapy from March 2019 to November 2022 in the Department of Otorhinolaryngology Head and Neck Surgery of the Tianjin First Central Hospital were retrospectively analyzed. Among them, 10 cases received radiotherapy and 22 cases did not receive radiotherapy. The radiotherapy group received irradiation with a large divided dose of 50 kV low-energy X-rays. The mode of fractionation radiotherapy was as follows: the first was 10 Gy of intraoperative radiation therapy and the second was 8 Gy on the 3rd postoperative day for a total of 18 Gy. The local efficacy and skin radiation reaction were observed at a follow-up of 8-52 months. Results:The median follow-up was 26 months, and as of the date of the last follow-up, 9 cases were cured and 1 case was ineffective in the radiotherapy group, with an effective rate of 90.0%, while 9 cases were cured and 13 cases were ineffective in the no-radiotherapy group, with an effective rate of 40.9%. The recurrence of ear keloids was not related to the side, site, or etiology of the patient's onset（P>0.05）. Recurrence was related to whether or not the patients received radiotherapy（χ²=4.885, P<0.05）, and the recurrence rate in the radiotherapy group（10.0%） was significantly lower than that in the non-radiotherapy group（59.1%）. Conclusion:Surgical excision combined with low-energy X-ray irradiation therapy is an effective method of treating keloids in the ear, especially with intraoperative radiation therapy can achieve more satisfactory results.

Modified technique of Hepatojejunostomy for biliary tract reconstruction after resection of tumors affecting the perihilar region: a case series.

BACKGROUNDS: Radical resection is the most effective treatment for perihilar tumors. Biliary tract reconstruction after resection is one of the key steps in this surgery. Mucosa-to-mucosa cholangiojejunostomy is traditionally performed, in which the bile ducts at the resection margin are separately anastomosed to the jejunum. However, this approach is associated with long operative time and high risk of postoperative complications. The present study presents a modified technique of hepatojejunostomy and its outcomes. METHODS: The data of patients who underwent hepatojejunostomy using the modified technique at the Department of Hepatobiliary Surgery, Daping Hospital, Army Medical University, Chongqing, China, from January 2016 to December 2021, were retrospectively analyzed. RESULTS: A total of 13 patients with perihilar tumors underwent R0 resection and bilioenteric reconstruction using the modified hepatojejunostomy technique during the study period. During the operation, the alignment of the bile duct stumps was improved, the posterior wall of the anastomosis was reinforced, internal stents were placed in the smaller bile ducts, external stents were placed in the larger bile ducts, and hepatojejunostomy was performed using 4 - 0 prolene. No serious postoperative complications, such as death or bile leakage, occurred during the hospitalization. Furthermore, there were no cases of biliary stricture or cholangitis after the six-month follow-up period. CONCLUSION: The modified hepatojejunostomy technique is a safe and effective technique of biliary reconstruction after the resection of perihilar tumors. This can be easily performed for difficult cases with multiple bile ducts that require reconstruction after resection.

Electrical Doping of Metal Halide Perovskites by Co-Evaporation and Application in PN Junctions.

Electrical doping of semiconductors is a revolutionary development that enabled many electronic and optoelectronic technologies. While doping of many inorganic and organic semiconductors is well-established, controlled electrical doping of metal halide perovskites (MHPs) is yet to be demonstrated. In this work, efficient n- and p-type electrical doping of MHPs by co-evaporating the perovskite precursors alongside organic dopant molecules is achieved. It is demonstrated that the Fermi level can be shifted by up to 500 meV toward the conduction band and by up to 400 meV toward the valence band by n- and p-doping, respectively, which increases the conductivity of the films. The doped layers are employed in PN and NP diodes, showing opposing trends in rectification. Demonstrating controlled electrical doping by a scalable, industrially relevant deposition method opens the route to developing perovskite devices beyond solar cells, such as thermoelectrics or complementary logic.

Neuronal and Molecular Mechanisms Underlying Chronic Pain and Depression Comorbidity in the Paraventricular Thalamus.

Patients with chronic pain often develop comorbid depressive symptoms, which makes the pain symptoms more complicated and refractory. However, the underlying mechanisms are poorly known. Here, in a repeated complete Freund's adjuvant (CFA) male mouse model, we reported a specific regulatory role of the paraventricular thalamic nucleus (PVT) glutamatergic neurons, particularly the anterior PVT (PVA) neurons, in mediating chronic pain and depression comorbidity (CDC). Our c-Fos protein staining observed increased PVA neuronal activity in CFA-CDC mice. In wild-type mice, chemogenetic activation of PVA glutamatergic neurons was sufficient to decrease the 50% paw withdrawal thresholds (50% PWTs), while depressive-like behaviors evaluated with immobile time in tail suspension test (TST) and forced swim test (FST) could only be achieved by repeated chemogenetic activation. Chemogenetic inhibition of PVA glutamatergic neurons reversed the decreased 50% PWTs in CFA mice without depressive-like symptoms and the increased TST and FST immobility in CFA-CDC mice. Surprisingly, in CFA-CDC mice, chemogenetically inhibiting PVA glutamatergic neurons failed to reverse the decrease of 50% PWTs, which could be restored by rapid-onset antidepressant S-ketamine. Further behavioral tests in chronic restraint stress mice and CFA pain mice indicated that PVA glutamatergic neuron inhibition and S-ketamine independently alleviate sensory and affective pain. Molecular profiling and pharmacological studies revealed the 5-hydroxytryptamine receptor 1D (Htr1d) in CFA pain-related PVT engram neurons as a potential target for treating CDC. These findings identified novel CDC neuronal and molecular mechanisms in the PVT and provided insight into the complicated pain neuropathology under a comorbid state with depression and related drug development.

Sample size determination for interval estimation of the prevalence of a sensitive attribute under non-randomized response models.

A sufficient number of participants should be included to adequately address the research interest in the surveys with sensitive questions. In this paper, sample size formulas/iterative algorithms are developed from the perspective of controlling the confidence interval width of the prevalence of a sensitive attribute under four non-randomized response models: the crosswise model, parallel model, Poisson item count technique model and negative binomial item count technique model. In contrast to the conventional approach for sample size determination, our sample size formulas/algorithms explicitly incorporate an assurance probability of controlling the width of a confidence interval within the pre-specified range. The performance of the proposed methods is evaluated with respect to the empirical coverage probability, empirical assurance probability and confidence width. Simulation results show that all formulas/algorithms are effective and hence are recommended for practical applications. A real example is used to illustrate the proposed methods.

The complete chloroplast genome of Philodendron hederaceum (Jacq.) Schott 1829 (Alismatales: Araceae).

Philodendron hederaceum (Jacq.) Schott 1829, a species of the Araceae family, is a foliage plant of ornamental value. The complete chloroplast genome sequence of Philodendron hederaceum was obtained by the de novo assembly of NovaSeq 6000 (Illumina Co., San Diego, CA) paired-end short reads and Oxford Nanopore long reads. The complete chloroplast genome of P. hederaceum was 168,609 bp in length, with a large single-copy (LSC) region of 94,393 bp, a small single-copy (SSC) region of 25,774 bp, and a pair of identical inverted repeat regions (IRs) of 24,221 bp. The genome contained a total of 129 genes, including 85 protein-coding genes, 36 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. The phylogenetic analysis of P. hederaceum with 19 related species and two outgroup species revealed the closest taxonomical relationship with Philodendron lanceolatum in the Araceae family.

A novel experimental setup for axial-torsional coupled vibration impact-assisted PDC drill bit drilling.

The geological conditions of hot dry rock (HDR) reservoirs are complex. The geothermal mining of HDR faces major challenges in the drilling and construction of wells, fracturing to create storage, and flowing to extract heat. Vibration impacts help improve the rock-breaking efficiency, where the axial-torsional coupled vibration impact technology can increase the bit penetration depth and reduce the stick-slip effect. To study the feasibility and efficiency of the axial-torsional-coupled vibration impact-assisted Polycrystalline Diamond Compact (PDC) bit to break high-temperature and high-pressure rocks, a new experimental setup was designed. The system includes a drilling fluid circulation system, an axial-torsional coupled impact drilling system, a formation simulation system, and a data acquisition and control system. This setup can produce a rock-breaking torque of 2000 N·m, a drilling speed of 200 rpm, a weight on bit of 100 kN, an axial vibration frequency of 100 Hz, and a torsional vibration frequency of 50 Hz. It can simulate the formation pressure of 70 MPa and the rock temperature of 400 °C. A series of rock-breaking drilling experiments were successfully conducted using this setup. The results show that the axial-torsional coupled vibration-impact assisted PDC bit has a good performance in breaking high-temperature and hard rocks, which can accelerate the application of this new technology in deep formation drilling.

Suppression of Randomness in Electrically Pumped Random Lasing from a ZnO Film-Based Light-Emitting Device on Silicon.

We report on the suppressed randomness in electrically pumped random lasing (RL) from a light-emitting device (LED) based on a metal-insulator-semiconductor (MIS) structure of Au/SiOx (x < 2)/ZnO on a silicon substrate, by means of patterning the light-emitting ZnO polycrystalline film into a number of square blocks separated by streets that are filled with the SiOx insulator. It is found that the RL modes can be remarkably reduced by shrinking the blocks in the absence of interblock optical coupling. Meanwhile, with the imposition of interblock optical coupling by shrinking the streets, the RL modes can be further reduced, and more importantly, the strongest mode wavelength is stabilized around 380 nm, where the ZnO film exhibits the largest optical gain.

Mucormycosis mimicking portal hypertensive haemorrhage as a complication of alcoholic liver cirrhosis: a case report.

Mucor is a rare cause of gastrointestinal ulcers. This case describes a case of mucormycosis that occurred in a patient with liver cirrhosis who was hospitalized to accept a splenectomy for traumatic splenic rupture. During the perioperative period, the patient developed upper gastrointestinal bleeding(UGIB), which was diagnosed as mucormycosis-related gastric ulcer according to gastroscopy. Patients with liver cirrhosis often get UGIB for Portal hypertension, but they also can develop UGIB for multiple other reasons, including infectious ulcers for immunosuppression. The case emphasizes the importance of excluding fungal-induced ulcer haemorrhage before diagnosing Portal hypertensive-induced variceal haemorrhage in patients with liver cirrhosis.

Multiple integrated social stress induces depressive-like behavioral and neural adaptations in female C57BL/6J mice.

Despite women representing most of those affected by major depression, preclinical studies have focused almost exclusively on male subjects, partially due to a lack of ideal animal paradigms. As the persistent need regarding the sex balance of neuroscience research and female-specific pathology of mental disorders surges, the establishment of natural etiology-based and systematically validated animal paradigms for depression with female subjects becomes an urgent scientific problem. This study aims to establish, characterize, and validate a "Multiple Integrated Social Stress (MISS)" model of depression in female C57BL/6J mice by manipulating and integrating daily social stressors that females are experiencing. Female C57BL/6J mice randomly experienced social competition failure in tube test, modified vicarious social defeat stress, unescapable overcrowding stress followed by social isolation on each day, for ten consecutive days. Compared with their controls, female MISS mice exhibited a relatively decreased preference for social interaction and sucrose, along with increased immobility in the tail suspension test, which could last for at least one month. These MISS mice also exhibited increased levels of blood serum corticosterone, interleukin-6 L and 1ß. In the pharmacological experiment, MISS-induced dysfunctions in social interaction, sucrose preference, and tail suspension tests were amended by systematically administrating a single dose of sub-anesthetic ketamine, a rapid-onset antidepressant. Compared with controls, MISS females exhibited decreased c-Fos activation in their anterior cingulate cortex, prefrontal cortex, nucleus accumbens and some other depression-related brain regions. Furthermore, 24 h after the last exposure to the paradigm, MISS mice demonstrated a decreased center zone time in the open field test and decreased open arm time in the elevated plus-maze test, indicating anxiety-like behavioral phenotypes. Interestingly, MISS mice developed an excessive nesting ability, suggesting a likely behavioral phenotype of obsessive-compulsive disorder. These data showed that the MISS paradigm was sufficient to generate pathological profiles in female mice to mimic core symptoms, serum biochemistry and neural adaptations of depression in clinical patients. The present study offers a multiple integrated natural etiology-based animal model tool for studying female stress susceptibility.

Towards low-temperature processing of efficient γ-CsPbI3 perovskite solar cells.

Inorganic cesium lead iodide (CsPbI3) perovskite solar cells (PSCs) have attracted enormous attention due to their excellent thermal stability and optical bandgap (∼1.73 eV), well-suited for tandem device applications. However, achieving high-performance photovoltaic devices processed at low temperatures is still challenging. Here we reported a new method for the fabrication of high-efficiency and stable γ-CsPbI3 PSCs at lower temperatures than was previously possible by introducing the long-chain organic cation salt ethane-1,2-diammonium iodide (EDAI2) and regulating the content of lead acetate (Pb(OAc)2) in the perovskite precursor solution. We find that EDAI2 acts as an intermediate that can promote the formation of γ-CsPbI3, while excess Pb(OAc)2 can further stabilize the γ-phase of CsPbI3 perovskite. Consequently, improved crystallinity and morphology and reduced carrier recombination are observed in the CsPbI3 films fabricated by the new method. By optimizing the hole transport layer of CsPbI3 inverted architecture solar cells, we demonstrate efficiencies of up to 16.6%, surpassing previous reports examining γ-CsPbI3 in inverted PSCs. Notably, the encapsulated solar cells maintain 97% of their initial efficiency at room temperature and under dim light for 25 days, demonstrating the synergistic effect of EDAI2 and Pb(OAc)2 in stabilizing γ-CsPbI3 PSCs.

Electric field promotes dermal fibroblast transdifferentiation through activation of RhoA/ROCK1 pathway.

With the increased incidence of age-related and lifestyle-related diseases, chronic wounds are sweeping the world, where recent studies reveal that dysfunction of fibroblast plays an indispensable role. Endogenous electric field (EF) generated by skin wound disrupting an epithelial layer has been used as an alternative clinical treatment in chronic wound by modulating cellular behaviours, including fibroblasts transdifferentiation. Although many molecules and signaling pathways have been reported associated with fibroblasts transdifferentiation, studies investigating how the electric field affects the cellular pathways have been limited. For this purpose, a model of electric field treatment in vitro was established, where cells were randomly divided into control and electrified groups. The changes of protein expression and distribution were detected under different conditions, along with Zeiss imaging system observing the response of cells. Results showed that fibroblast transdifferentiation was accompanied by increased expression of a-SMA and extracellular matrix (COL-1 and COL-3) under the EF. Simultaneously, fibroblast transdifferentiation was also consistent with changes of cell arrangement and enhanced motility. Furthermore, we found that electric field activated RhoA signaling pathways activity. Y-27632, a RhoA inhibitor, which was used to treat fibroblasts, resulted in reduced transdifferentiation. The connection between electric field and RhoA signaling pathways is likely to be significant in modulating fibroblast transdifferentiation in acute injury and tissue remodeling, which provides an innovative idea for the molecular mechanism of EF in promoting chronic wound healing.

Design and manufacturing of biomimetic scaffolds for bone repair inspired by bone trabeculae.

Porous scaffold (PorS) implants, particularly those that mimic the structural features of natural cancellous bone (NCanB), are increasingly essential for the treatment of large-area bone defects. However, the mechanical properties of NCanB-based bionic bone scaffold (BioS) and its performance as a bone repair material have not been fully explored. This study investigates the effect of bionic structure parameters on the mechanical properties and bone reconstruction performance of BioS. Using laser powder bed fusion (L-PBF) technology, different BioS with various structural parameters were created and evaluated using Micro-CT, compression testing, Finite Element (FE) Simulation, and computational fluid dynamics (CFD), and compared to commonly used clinical PorS. Assess the capacity of the BioS scaffold to support and enhance bone reconstruction following implantation through the evaluation of its mechanical properties, permeability, and fluid shear stress (FSS). BioS-85-90 and BioS-80-50 showed suitable mechanical properties, performed well in FE simulation of implantation, demonstrated outstanding abilities for osteoinductive ingrowth and bone tissue differentiation, and proved to be reliable materials for the reconstruction of bone defects. Therefore, BioS shows significant potential for clinical application as a bone reconstruction material, providing a solid foundation for the integration of tissue engineering and bionic design.

Synergistic enhanced activation of peroxymonosulfate by heterojunction Co3O4-CuO@CN for removal of oxytetracycline: Performance, mechanism, and stability.

Metal-organic frameworks (MOFs) as precursors for catalysts has drawn growing attentions. In this study, heterojunction Co3O4-CuO doped carbon materials (noted as Co3O4-CuO@CN) were prepared by direct carbonization of CuCo-MOF in air. It was found that the Co3O4-CuO@CN-2 exhibited excellent catalytic activity with the highest Oxytetracycline (OTC) degradation rate of 0.0902 min-1 at 50 mg/L of Co3O4-CuO@CN-2 dosage, 2.0 mM of PMS and 20 mg/L of OTC, which was 4.25 and 4.96 times that of CuO@CN and Co3O4@CN, respectively. Furthermore, Co3O4-CuO@CN-2 was efficient over a wide pH range (pH 1.9-8.4), and possessed good stability and reusability without OTC degradation decrease after five consecutive uses at pH 7.0. In a comprehensive analysis, the rapid regeneration of Cu(II) and Co(II) is responsible for their excellent catalytic performance, and the p-p heterojunction structure formed between Co3O4 and CuO acts as an intermediary of electron transfer to accelerate PMS decomposition. Moreover, it was interesting to find that Cu rather than Co species played a vital role in the PMS activation. The quenching experiments and electron paramagnetic resonance demonstrated that .OH, SO4•-, and 1O2 were the reactive species responsible for oxidation of OTC and the non-radical pathway triggered by 1O2 was dominant.

Adulthood bisphenol A exposure induces anxiety in male mice via downregulation of alpha-1D adrenergic receptor in paraventricular thalamus.

Bisphenol A (BPA), a ubiquitous endocrine disrupting chemical, is widely used in household plastic products. Large amounts of evidence indicate prenatal and postnatal BPA exposure causes neurodevelopmental disorders such as anxiety and autism. However, the neuronal mechanisms underlying the neurotoxic effects of adulthood BPA exposure remain poorly understood. Here, we provided evidences that adult mice treated with BPA (0.45 mg/kg/day) during 3 weeks exhibited sex-specific anxiety like behaviors. We demonstrated that the BPA-induced anxiety in male mice, but not in female mice, was closely associated with hyperactivity of glutamatergic neurons in the paraventricular thalamus (PVT). Acute chemogenetic activation of PVT glutamatergic neurons caused similar effects on anxiety as observed in male mice exposed to BPA. In contrast, acute chemogenetic inhibition of PVT glutamatergic neurons reduced BPA-induced anxiety in male mice. Concomitantly, the BPA-induced anxiety was related with a down-regulation of alpha-1D adrenergic receptor in the PVT. Taken together, the present study indicated a previously unknown target region in the brain for neurotoxic effects of BPA on anxiety and implicated a possible molecular mechanism of action.

Neural and molecular investigation into the paraventricular thalamic-nucleus accumbens circuit for pain sensation and non-opioid analgesia.

The paucity of medications with novel mechanisms for pain treatment combined with the severe adverse effects of opioid analgesics has led to an imperative pursuit of non-opioid analgesia and a better understanding of pain mechanisms. Here, we identify the putative glutamatergic inputs from the paraventricular thalamic nucleus to the nucleus accumbens (PVTGlut→NAc) as a novel neural circuit for pain sensation and non-opioid analgesia. Our in vivo fiber photometry and in vitro electrophysiology experiments found that PVTGlut→NAc neuronal activity increased in response to acute thermal/mechanical stimuli and persistent inflammatory pain. Direct optogenetic activation of these neurons in the PVT or their terminals in the NAc induced pain-like behaviors. Conversely, inhibition of PVTGlut→NAc neurons or their NAc terminals exhibited a potent analgesic effect in both naïve and pathological pain mice, which could not be prevented by pretreatment of naloxone, an opioid receptor antagonist. Anterograde trans-synaptic optogenetic experiments consistently demonstrated that the PVTGlut→NAc circuit bi-directionally modulates pain behaviors. Furthermore, circuit-specific molecular profiling and pharmacological studies revealed dopamine receptor 3 as a candidate target for pain modulation and non-opioid analgesic development. Taken together, these findings provide a previously unknown neural circuit for pain sensation and non-opioid analgesia and a valuable molecular target for developing future safer medication.

LINC00632 relates to milder Th1/Th2 imbalance, attenuated nasal symptoms, and better response to therapy in allergic rhinitis patients.

OBJECTIVE: Long intergenic noncoding RNA 00632 (LINC00632) regulates nasal inflammation and CD4+ T cell differentiation into T helper (Th) 2 cells in allergic rhinitis (AR). This study aimed to explore the relationship between LINC00632 and Th1/Th2 balance, and the clinical value of LINC00632 in AR patients. METHODS: In total, 120 AR patients, 20 non-atopic obstructive snoring patients as disease controls (DCs), and 20 healthy controls (HCs) were recruited. Their LINC00632 expressions in peripheral blood mononuclear cells were detected by RT-qPCR. RESULTS: LINC00632 expression was declined in AR patients compared with DCs and HCs (both P ˂ 0.001). Moreover, LINC00632 could distinguish AR patients from DCs with an area under curve (AUC) of 0.795 (95% confidence interval [CI]: 0.701-0.889), and from HCs with an AUC of 0.895 (95%CI: 0.831-0.960). LINC00632 was positively related to Th1 cells (P = 0.037) and Th1/Th2 axis (P ˂ 0.001) in AR patients. In addition, LINC00632 was inversely associated with Th2 cells (P ˂ 0.001) and interleukin (IL)-4 (P = 0.010) in AR patients. Besides, LINC00632 was negatively related to rhinorrhea score (P = 0.019), itching score (P = 0.008), sneezing score (P = 0.004), and total nasal symptom score (TNSS) (P ˂ 0.001), but no correlation between LINC00632 and congestion score was observed (P = 0.093). During treatment, LINC00632 was elevated, while TNSS score was reduced (both P ˂ 0.001). Furthermore, LINC00632 increment was associated with the reduction of TNSS score during the therapy (P = 0.005). CONCLUSION: LINC00632 relates to milder Th1/Th2 imbalance, attenuated nasal symptoms, and better response during 4-week therapy in AR patients.

LINC00632 relates to milder Th1/Th2 imbalance, attenuated nasal symptoms, and better response to therapy in allergic rhinitis patients

Objective: Long intergenic noncoding RNA 00632 (LINC00632) regulates nasal inflammation and CD4+ T cell differentiation into T helper (Th) 2 cells in allergic rhinitis (AR). This study aimed to explore the relationship between LINC00632 and Th1/Th2 balance, and the clinical value of LINC00632 in AR patients. Methods: In total, 120 AR patients, 20 non-atopic obstructive snoring patients as disease controls (DCs), and 20 healthy controls (HCs) were recruited. Their LINC00632 expressions in peripheral blood mononuclear cells were detected by RT-qPCR. Results: LINC00632 expression was declined in AR patients compared with DCs and HCs (both P ˂ 0.001). Moreover, LINC00632 could distinguish AR patients from DCs with an area under curve (AUC) of 0.795 (95% confidence interval [CI]: 0.701–0.889), and from HCs with an AUC of 0.895 (95%CI: 0.831–0.960). LINC00632 was positively related to Th1 cells (P = 0.037) and Th1/Th2 axis (P ˂ 0.001) in AR patients. In addition, LINC00632 was inversely associated with Th2 cells (P ˂ 0.001) and interleukin (IL)-4 (P = 0.010) in AR patients. Besides, LINC00632 was negatively related to rhinorrhea score (P = 0.019), itching score (P = 0.008), sneezing score (P = 0.004), and total nasal symptom score (TNSS) (P ˂ 0.001), but no correlation between LINC00632 and congestion score was observed (P = 0.093). During treatment, LINC00632 was elevated, while TNSS score was reduced (both P ˂ 0.001). Furthermore, LINC00632 increment was associated with the reduction of TNSS score during the therapy (P = 0.005). Conclusion: LINC00632 relates to milder Th1/Th2 imbalance, attenuated nasal symptoms, and better response during 4-week therapy in AR patients (AU)

A phase 1/2, open-label, multicenter study of isatuximab in combination with cemiplimab in patients with lymphoma.

Patients with relapsed or refractory lymphoma have limited treatment options, requiring newer regimens. In this Phase 1/2 study (NCT03769181), we assessed the safety, efficacy, and pharmacokinetics of isatuximab (Isa, anti-CD38 antibody) in combination with cemiplimab (Cemi, anti-programmed death-1 [PD-1] receptor antibody; Isa + Cemi) in patients with classic Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL), and peripheral T-cell lymphoma (PTCL). In Phase 1, we characterized the safety and tolerability of Isa + Cemi with planned dose de-escalation to determine the recommended Phase 2 dose (RP2D). Six patients in each cohort were treated with a starting dose of Isa + Cemi to determine the RP2D. In Phase 2, the primary endpoints were complete response in Cohort A1 (cHL anti-PD-1/programmed death-ligand 1 [PD-L1] naïve), and objective response rate in Cohorts A2 (cHL anti-PD-1/PD-L1 progressors), B (DLBCL), and C (PTCL). An interim analysis was performed when the first 18 (Cohort A1), 12 (Cohort A2), 17 (Cohort B), and 11 (Cohort C) patients in Phase 2 had been treated and followed up for 24 weeks. Isa + Cemi demonstrated a manageable safety profile with no new safety signals. No dose-limiting toxicities were observed at the starting dose; thus, the starting dose of each drug was confirmed as the RP2D. Based on the Lugano 2014 criteria, 55.6% (Cohort A1), 33.3% (Cohort A2), 5.9% (Cohort B), and 9.1% (Cohort C) of patients achieved a complete or partial response. Pharmacokinetic analyses suggested no effect of Cemi on Isa exposure. Modest clinical efficacy was observed in patients with cHL regardless of prior anti-PD-1/PD-L1 exposure. In DLBCL or PTCL cohorts, interim efficacy analysis results did not meet prespecified criteria to continue enrollment in Phase 2 Stage 2. Isa + Cemi did not have a synergistic effect in these patient populations.