Search

Nicotine, the primary addictive substance in tobacco, produces the psychomotor, rewarding, and reinforcing effects of tobacco dependence by stimulating nicotinic acetylcholine receptors (nAChRs) in the brain. The present study determined that α4β2 nAChRs regulate locomotor sensitization by altering dopamine concentration in the nucleus accumbens (NAc) after systemic challenge exposure to whole cigarette smoke condensate (WCSC). Rats were administered subcutaneous injection of WCSC (0.2 mg/kg nicotine/day) for 7 consecutive days and then re-exposed to WCSC after 3 days of withdrawal. Challenge exposure to WCSC significantly increased locomotor activity. This increase was decreased by the subcutaneous injection of the α4β2 nAChR antagonist, DHβE (3 mg/kg), but not by the intraperitoneal injection of the α7 nAChR antagonist, MLA (5 mg/kg). In parallel with a decrease in locomotor activity, blockade of α4β2 nAChRs with DHβE decreased dopamine concentration in the NAc which was elevated by challenge exposure to WCSC. These findings suggest that challenge WCSC leads to the expression of locomotor sensitization by elevating dopamine concentration via stimulation of α4β2 nAChRs expressed in neurons of the NAc in rats.

The metal halide Cs

Most therapeutic peptides available on the market today are naturally occurring hormones or protein fragments that were serendipitously discovered to possess therapeutic effects. However, the limited repertoire of available natural resources presents difficulties for the development of new peptide drug candidates. Traditional peptides possess several shortcomings that must be addressed for biomedical applications, including relatively low affinity or specificity toward biological targets compared to antibody- and protein scaffold-based affinity molecules, poor in vivo stability owing to rapid enzymatic degradation, and rapid clearance from circulation owing to their small size. Going forward, it will be increasingly important for scientists to develop novel classes of high-affinity and -specificity peptides against desired targets that mitigate these limitations while remaining compatible with pharmaceutical manufacturing processes. Recently, several highly constrained, artificial cyclic peptides have emerged as platforms capable of generating high-affinity peptide binders against various disease-associated protein targets by combining with phage or mRNA display method, some of which have entered clinical trials. In contrast, although linear peptides are relatively easy to synthesize cost-effectively and modify site-specifically at either N- or C-termini compared to cyclic peptides, there have been few linear peptide-based platforms that can provide high-affinity and -specificity peptide binders.In this Account, we describe the creation and development of a novel class of high-affinity peptides, termed "aptide"-from the Latin word "aptus" meaning "to fit" and "peptide"-and summarize their biomedical applications. In the first part, we consider the design and creation of aptides, with a focus on their unique structural features and binding mode, and address screening and identification of target protein-specific aptides. We also discuss advantages of the aptide platform over ordinary linear peptides lacking preorganized structures in terms of the affinity and specificity of identified peptide binders against target molecules. In the second part, we describe the potential biomedical applications of various target-specific aptides, ranging from imaging and therapy to theranostics, according to the types of aptides and diseases. We show that certain aptides can not only bind to a target protein but also inhibit its biological function, thereby showing potential as therapeutics per se. Further, aptides specific for cancer-associated protein antigens can be used as escort molecules or targeting ligands for delivery of chemotherapeutics, cytokine proteins, and nanomedicines, such as liposomes and magnetic particles, to tumors, thereby substantially improving therapeutic effects. Finally, we present a strategy capable of overcoming the critical issue of short blood circulation time associated with most peptides by constructing a hybrid system between an aptide and a hapten cotinine-specific antibody.

Most red-green-blue and depth (RGB-D) motion-recognition technologies employ both depth and RGB cameras to recognize a user's body. However, motion-recognition solutions using a single RGB-D camera struggle with rotation recognition depending on the device-user distance and field-of-view. This paper proposes a near-real-time rotational-coordinate-correction method that rectifies a depth error unique Microsoft Kinect by using the symmetry of the depth coordinates of the human body. The proposed method is most effective within 2 m, a key range in which the unique depth error of Kinect occurs, and is anticipated to be utilized in applications requiring low cost and fast installation. It could also be useful in areas such as media art that involve unspecified users because it does not require a learning phase. Experimental results indicate that the proposed method has an accuracy of 85.38%, which is approximately 12% higher than that of the reference installation method.

Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (MTB), is a serious infectious disease with high infection and mortality rates and is a public health problem around the world. According to the World Health Organization (WHO) report, one-third of the world's population is latently infected with MTB, and 5 to 10% of those with latent TB infection (LTBI) have the potential to develop active TB once in their lifetime. Therefore, TB management for promptly distinguishing LTBI from active TB and for proper treatment is important. LTBI is currently diagnosed using the tuberculin skin test (TST) and interferon gamma (IFN-γ) release assay (IGRA). However, this test is substantially limited by its inability to distinguish active TB from LTBI. It is necessary to discover indicators that can be used for effective TB management and to develop diagnostic methods. In the present study, we used IGRA and complete blood count (CBC) analysis for discrimination of active TB, LTBI, and healthy control groups. The results showed that the number of WBC was significantly increased in the group with active TB (p

Introduction Nicotine increases reinforcing effects of cigarette smoking by upregulating glutamate and dopamine releases via stimulation of nicotinic acetylcholine receptors (nAChRs) in the dorsal striatum (CPu). The present study was conducted to evaluate whether non-nicotine substances in cigarette smoke potentiate nicotine-induced behaviors by increasing glutamate and dopamine concentrations in the CPu. Aims and Methods Changes in the levels of glutamate and dopamine in the CPu were analyzed using a glutamate colorimetric assay and dopamine enzyme-linked immunosorbent assay, respectively, after repeated administration of nicotine or whole cigarette smoke condensate (WCSC) in male Sprague-Dawley rats. Changes in locomotion and drug-taking behavior were analyzed using the measurements of locomotor activity and self-administration under a fixed ratio 1 schedule in response to repeated administration of nicotine or WCSC. Results Repeated subcutaneous (s.c.) injections of nicotine (0.25 mg/kg/day) for 7 consecutive days significantly increased the levels of glutamate and dopamine in the CPu. Similar results were obtained from repeated injections of WCSC (0.25 mg/kg nicotine/day, s.c.) extracted from 3R4F Kentucky reference cigarettes. Parallel with the increases in the neurotransmitter levels in the CPu, both nicotine and WCSC increased locomotor activity and self-administration (0.03 mg/kg nicotine/infusion). However, repeated injections of WCSC did not change the nicotine-induced increases in neurotransmitter levels, locomotor activity, and self-administration. Conclusions Nicotine rather than non-nicotine substances in WCSC play a major role in potentiating behavioral sensitization and drug-taking behavior via elevation of glutamate and dopamine concentrations in the CPu of rats. Implications WCSC does not augment the nicotine-induced increases in behavioral sensitization, drug-taking behavior, and glutamate and dopamine concentrations, suggesting that non-nicotine substances do not potentiate the nicotine-induced behaviors by increasing the concentrations of the neurotransmitters in the CPu. These findings imply that nicotine, but not non-nicotine substances in WCSC, may be a major contributor that induces tobacco dependence in rats.

Hair loss due to medical conditions, such as alopecia, male pattern baldness, and cancer chemotherapy treatment, has been a common problem for many individuals. Cyclosporin A (CsA), a fungal metabolite, has been reported to be a hair growth modulatory agent and is a potential drug for hair regeneration. However, the effect of topical application of CsA is limited by its poor water solubility. Several delivery systems developed to enhance its solubility still showed poor skin penetration. To overcome these limitations, in this study, we have developed a novel chitosan nanocapsule platform using Pluronic F127 and chitosan without any chemical crosslinking or complicated preparation steps for the enhanced water solubility and high transdermal penetration of CsA. The chitosan nanocapsules (ChiNCs) optimized in terms of structural stability by using chitosan with various molecular weights ranging from 3 to 100 kDa enhanced the skin permeation of CsA through human cadaver skin in vitro. Topical administration of the CsA loaded ChiNCs increased the hair follicles by c.a. 7 times higher than that of the control group, and effectively induced hair growth in C57BL/6 mice in vivo. These results suggest that ChiNCs could be used as a platform for effective transdermal delivery of various hydrophobic drugs.

Optoelectronic memory devices, whose states can be controlled using electrical optical signals, are receiving much attention for their potential applications in image sensing and parallel data transmission and processes. Here, we report MoS2-based devices with top floating gates of Au, graphene, and MoS2. Unlike conventional floating gate memory devices, our devices have the photoresponsive floating gate at the top, acting as a charge trapping layer. Stable and reliable switching with an on/off ratio of ∼106 and a retention time of >104 s is achieved by illumination with 405 nm light pulses as well as application of gate voltage pulses. However, upon illumination with 532 or 635 nm light pulses, multilevel optical memory effects are observed, which are dependent on the wavelength and the optical exposure dosage. In addition, compared to the device employing a graphene floating gate, the device with an MoS2 floating gate is more sensitive to light, suggesting that the multilevel optical memory properties originate from photoexcited carriers in the top floating gate and can be modulated by adjusting the top floating gate materials. The structure of the top floating gate may open up a new way to novel optoelectronic memory devices.

Background One-third of cervical cancer patients are still diagnosed at advanced stages. The five-year survival rate is decreased in about 50% of advanced stage cervical cancer patients worldwide, and the clinical outcomes are remarkably varied and difficult to predict. One of the miRNAs known to be associated with cancer tumorigenesis is miR-944. However, the prognostic value of miR-944 in cervical cancer has not been fully investigated. The aim of this study was to analyze clinical significance and prognostic value of miR-944 in cervical cancer. Methods The expression levels of miR-944 were detected using quantitative reverse transcription polymerase chain reaction in five types of cervical cancer cell lines and 116 formalin-fixed paraffin-embedded (FFPE) cervical tissues. The association between the expression levels of miR-944 and prognostic value was analyzed using the Kaplan-Meier analysis and Cox proportional hazards model. Results The expression levels of miR-944 in cervical cancer tissues were significantly higher compared with those in normal tissues (P

Fisheries capture has plateaued, creating ever-greater reliance on aquaculture to feed growing populations. Aquaculture volumes now exceed those of capture fisheries globally1,2, with China dominating production through major land-use change; more than half of Chinese freshwater aquaculture systems have been converted from paddy fields1,3. However, the greenhouse gas implications of this expansion have yet to be effectively quantified. Here, we measure year-round methane (CH4), nitrous oxide (N2O) and carbon dioxide (CO2) emissions from paddy fields and new, extensively managed crab aquaculture ponds. The conversion increased associated global warming potentials from 8.15 ± 0.43 to 28.0 ± 4.1 MgCO2eq ha−1, primarily due to increased CH4 emissions. After compiling a worldwide database of different freshwater aquaculture systems, the top 21 producers were estimated to release 6.04 ± 1.17 TgCH4 and 36.7 ± 6.1 GgN2O in 2014. We found that 80.3% of the total CH4 emitted originated in shallow earthen aquaculture systems, with far lower emissions from intensified systems with continuous aeration4. We therefore propose that greater adoption of aerated systems is urgently required to address globally significant rises in CH4 emissions from the conversion of paddy fields to aquaculture. China dominates the global growth in aquaculture food production, primarily through massive conversion of paddy fields to crab ponds. This land conversion is greatly increasing methane emissions but these can be significantly reduced by water aeration.

Background: CT-P16 is a proposed biosimilar to FDA approved reference bevacizumab (BV), namely Avastin®. This trial (NCT03676192) compared the efficacy and safety of CT-P16 and BV in patients with metastatic or recurrent non-squamous NSCLC. Methods: This double blind, randomized, multicenter study randomly assigned patients to CT-P16 or BV with carboplatin and paclitaxel, up to 6 cycles (Induction Period), followed by maintenance CT-P16 or BV monotherapy until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR) during the Induction Period. ORR includes complete or partial responses based on RECIST v1.1 assessed by an independent reviewer. Secondary endpoints were Quality of life (QoL), PK, safety, and immunogenicity. Results: A total of 689 patients were randomized (CT-P16: 342, BV: 347). The baseline characteristics were well balanced. ORRs were similar between the two treatment arms and the 90% confidence intervals (CIs) for the risk ratio estimate (0.7368, 1.3572) and 95% CIs for risk difference estimate (±12.5%) were within the equivalence margin in both ITT (intent-to-treat) and PP (per-protocol) sets. QoL results (QLQ-C30 and QLQ-LC13) and PK parameter (Ctrough) were comparable between the two treatment arms. The overall incidence of treatment-emergent adverse events (TEAEs), serious AEs (TESAEs), AEs leading to discontinuation, and AEs leading to death was similar between the two treatment arms (96.2% vs. 92.4%, 19.4% vs. 20.1%, 15.1% vs. 14.5%, and 6.4% vs. 6.4% for the CT-P16 and BV treatment arm, respectively). The incidence of treatment-emergent anti-drug antibodies was comparable (14.2% vs. 16.0%). Conclusions: This study demonstrated that CT-P16 is equivalent to BV as measured by ORR in patients with metastatic or recurrent adenocarcinoma of the lung. Other endpoints including PK, QoL, safety and immunogenicity were comparable. Primary endpoint ITT PP CT-P16 (N=342) BV (N=347) CT-P16 (N=318) BV (N=303) Independent reviewer ORR (%) 95% CI 42.40 (37.16 - 47.64) 42.07 (36.88 - 47.27) 45.28 (39.81 - 50.75) 47.19 (41.57 - 52.82) Risk ratio estimate (90% CI) 1.0136 (0.8767, 1.1719) 0.9662 (0.8387, 1.1132) Risk difference estimate (%) (95% CI) 0.40 (-7.02, 7.83) -1.90 (-9.80, 6.00) Investigator ORR (%) 95% CI 43.86 (38.60 - 49.12) 39.19 (34.06 - 44.33) 46.54 (41.06 - 52.02) 43.89 (38.31 - 49.48) Risk ratio estimate (90% CI) 1.1234 (0.9683, 1.3032) 1.0648 (0.9209, 1.2313) Risk difference estimate (%) (95% CI) 4.87 (-2.53, 12.26) 2.90 (-4.99, 10.79) Citation Format: Yuichiro Ohe, Igor Bondarenko, Zoran Andric, Yuriy Ostapenko, Tudor Ciuleanu, Fedor Moiseenko, Tamta Makharadze, Sergii Shevnya, Alona Oleksiienko, Eduardo Yañez Ruiz, SungHyun Kim, KeumYoung Ahn, TaeHong Park, Sijin Park, JiEun Lee, MinJi Kim, Claire Verschraegen. Randomized phase III study comparing the efficacy and safety of CT-P16, a new biosimilar, to reference bevacizumab (Avastin®) in patients with metastatic or recurrent non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT551.

자궁경부암은 세계적으로 여성에서 네번째로 많이 진단되는 암이다. 개발 지수가 낮은 개발도상국이나 후진국에서는 자궁경부암의 발생률과 사망률이 훨씬 심각하다. 따라서 더 나은 진단법과 치료법이 시급하다. 인유두종바이러스가 자궁경부암 발생의 주요 원인으로 알려진 이후로 바이러스에 대한 검사가 세포검사ㆍ조직검사와 함께 자궁경부암을 진단하는데 일상적으로 쓰이고 있다. 하지만, HPV 검사에서 음성을 보이는 환자가 자궁경부암으로 발전하는 사례가 계속해서 발견되고 있다. 본 연구에서는 HPV 외에 자궁경부암의 원인으로 생각되는 인자들에 대해 분석하였다. 그 중에서도 에스트로겐 수용체 알파의 mRNA 발현양을 실시간 역전사 중합효소 연쇄반응을 통해 분석하였다. 에스트로겐 수용체 알파에 대해서는 예전부터 자궁내막을 성숙시키면서 동시에 자궁경부암의 발암 기전에 연관이 있을 것이라는 추측이 있었는데, 본 연구에서는 이에 대해 임상 검체를 통해 양적 분석을 진행하였다. ROC 곡선을 바탕으로, 85%의 민감도와 75%의 특이도를 확인할 수 있었는데, 이 값은 기존의 HPV 검사법보다 유사하거나 더 높은 값이었다. 나이, 병변의 심한 정도 등을 포함한 임상 정보를 바탕으로 회귀 분석한 결과 폐경 여부와 에스트로겐 수용체 알파의 발현양이 높은 연관성을 확인하였다. 본 연구는 예비 연구의 일종으로, 추후 연구에서 가능성이 확인된 호르몬과 폐경에 관련된 유전자를 대상으로 더 많은 검체로 분석해야 할 것이다.

A number of cancer-targeting peptide-drug conjugates (PDCs) have been explored as alternatives to antibody-drug conjugates (ADCs) for targeted cancer therapy. However, the much shorter circulation half-life of PDCs compared with ADCs in vivo has limited their therapeutic value and thus their translation into the clinic, highlighting the need to develop new approaches for extending the half-life of PDCs. Here, we report a new strategy for targeted cancer therapy of a PDC based on a molecular hybrid between an antihapten antibody and a hapten-labeled PDC. An anticotinine antibody (Abcot) was used as a model antihapten antibody. The anticancer drug SN38 was linked to a cotinine-labeled aptide specific to extra domain B of fibronectin (cot-APTEDB), yielding the model PDC, cot-APTEDB-SN38. The cotinine-labeled PDC showed specific binding to and cytotoxicity toward an EDB-overexpressing human glioblastoma cell line (U87MG) and also formed a hybrid complex (HC) with Abcot in situ, designated HC[cot-APTEDB-SN38/Abcot]. In glioblastoma-bearing mice, in situ HC[cot-APTEDB-SN38/Abcot] significantly extended the circulation half-life of cot-APTEDB-SN38 in blood, and it enhanced accumulation and penetration within the tumor and, ultimately, inhibition of tumor growth. These findings suggest that the present platform holds promise as a new, targeted delivery strategy for PDCs in anticancer therapy.

Rats express a positive emotional state by emitting 50-kHz ultrasonic vocalization (USV) calls in response to drug exposure. This study demonstrated the linking of glutamate receptors in the nucleus accumbens (NAc) to vocal expression of 50-kHz USV calls after repeated cocaine administration in freely moving rats. Repeated systemic injections of cocaine (20 mg/kg/day, i.p.) for seven consecutive days increased the number of 50-kHz USV calls. Intra-NAc core infusion of the broad-glutamate receptor antagonist, γDGG (50 nmol/side), decreased the repeated cocaine-induced increase in the number of 50-kHz USV calls. Intra-NAc core infusion of the N-methyl-D-aspartate (NMDA) receptor antagonist, MK801 (2 nmol/side), but not α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or kainic acid receptor antagonist, CNQX disodium salt (2 nmol/side), decreased the number of 50-kHz USV calls that had been elevated by repeated exposure to cocaine. Intra-NAc core infusion of the group I metabotropic glutamate receptor subtype 5 (mGluR5), MPEP (0.5 nmol/side), MTEP (15 nmol/side) and inositol-1,4,5-trisphosphate receptor blocker, xestospongin C (0.004 nmol/side) decreased the cocaine-induced increase in the number of USV calls. These data suggest that the NMDA receptor- and mGluR5-dependent increase in intracellular Ca2+ concentrations in the NAc core is linked to a positive emotional state after repeated exposure to cocaine in rats.

In the present study, we aimed to investigate whether an automated molecular diagnostic method based on PCR-reverse blot hybridization assay can discriminate between human Mycobacterium tuberculosis (MTB)-positive and -negative FFPE tissues and to compare the relative mRNA expression levels of various host immune markers between MTB-infected and uninfected human tissues using quantitative reverse transcription (qRT) PCR. A total of 52 human FFPE tissue samples from various regions of the body, including the lungs, lymph nodes, tendons, colon, and appendix, were collected and used for the molecular identification of Mycobacterium species and analysis of cytokine mRNA expression. As a result, IFN-γ, TNF-α, IP-10, CXCL9, CXCL11, and GM-CSF mRNA expression levels in MTB-infected tissues were significantly higher than those in uninfected samples. Additionally, the differences in the mRNA expression levels of IFN-γ, CXCL9, and GM-CSF between MTB-infected and uninfected tissues were statistically significant were statistically significant (p < 0.05). Correlation curve analysis indicated that the mRNA expression of IFN-γ was inversely proportional to that of IP-10 and that the mRNA expression levels of IFN-γ, TNF-α, CXCL9, CXCL11, GM-CSF, and TNFR were proportional and well-correlated. Furthermore, to establish marker profiles for detecting MTB infection, the statistically significant expression levels of three markers were combined. We confirmed that the combined profile of IFN-γ, CXCL9, and GM-CSF expression levels was statistically significant (P < 0.001). Although the mRNA expression patterns of host immune markers may vary according to MTB infection status, these patterns may be highly correlated and can be simultaneously used as an additional indicator for diagnosing TB.

There have been few reports on the kinetics of hemodialyzed (HD) patients’ immune responses in latent tuberculosis infection (LTBI). Therefore, in the present study, messenger ribonucleic acid (mRNA) expression levels of nine immune markers were analyzed to discriminate between HD patients with LTBI and healthy individuals. Nine cytokines and chemokines were screened through relative mRNA expression levels in whole blood samples after stimulation with Mycobacterium tuberculosis (MTB)-specific antigens from HD patients with LTBI (HD/LTBI), HD patients without LTBI, and healthy individuals, and results were compared with the QuantiFERON-TB Gold In-Tube (QFT-GIT) test. We confirmed that the C-C motif chemokine 11 (CCL11) mRNA expression level of the HD/LTBI group was significantly higher than the other two groups. Especially, the CCL11 mRNA expression level of the &gt, 0.7 IU/mL group in the QFT-GIT test was significantly higher than the &lt, 0.2 IU/mL group in the QFT-GIT test and the 0.2–0.7 IU/mL group in the QFT-GIT test (p = 0.0043). The present study reveals that the relative mRNA expression of CCL11 was statistically different in LTBI based on the current cut-off value (i.e., ≥0.35 IU/mL) and in the &gt, 0.7 IU/mL group. These results suggest that CCL11 mRNA expression might be an alternative biomarker for LTBI diagnosis in HD patients.

Purpose Modulated electro-hyperthermia (mEHT) may enhance the tumor response, although the effectiveness of combined neoadjuvant therapy remains unclear. Therefore, we investigated the role of mEHT with neoadjuvant therapy for locally advanced rectal cancer. Materials and methods Clinical data were analyzed for 120 patients who received neoadjuvant treatment for locally advanced rectal cancer (T3/4 or N+, M0) from May 2012 to December 2017. Capecitabine or 5-fluorouracil was administered along with radiotherapy. Patients were categorized into mEHT group (62 patients) and non-mEHT group (58 patients) depending on whether mEHT was added. Surgery was performed 6–8 weeks after the end of radiotherapy. Results The median age was 59 years (range, 33–83). The median radiation dose was significantly less for mEHT group (40 Gy) than for non-mEHT group (50.4 Gy). In mEHT group, 80.7% showed down-staging compared with 67.2% in non-mEHT group. For large tumors of more than 65 cm³ (mean), improved tumor regression was observed in 31.6% of mEHT group compared with 0% of non-mEHT group (p = .024). The gastrointestinal toxicity rate of mEHT group was 64.5%, which was found to be statistically significantly less than 87.9% of non-mEHT group (p = .010). The 2-year disease-free survival was 96% for mEHT group and 79% for non-mEHT group (p = .054). Conclusion The overall mEHT group had a comparable response and survival using less radiation dosing compared with standard care; the subgroup with large tumors showed improved efficacy for tumor regression after mEHT.

Background: One of the widely used diagnostic methods for Mycobacterium tuberculosis (MTB) infection is the acid-fast bacilli staining of formalin-fixed paraffin-embedded (FFPE) tissues; however, this method cannot discriminate between MTB and nontuberculous mycobacteria (NTM) species. Moreover, confirming tuberculosis (TB) using FFPE tissue specimens may be difficult owing to their low bacterial load. In addition, interference in molecular diagnostic assays, including polymerase chain reaction (PCR), may occur owing to fragmentation and genomic DNA cross-linkage in FFPE tissues formed during formalin fixation or paraffin-embedding procedures. Therefore, we aimed to investigate whether an automated molecular diagnostic method based on PCR-reverse blot hybridization assay can discriminate between human MTB-positive and -negative FFPE tissues and to compare the relative mRNA expression levels of various host immune markers between MTB-infected and uninfected human tissues using quantitative reverse transcription (qRT) PCR. A total of 52 human FFPE tissue samples from various regions of the body, including the lungs, lymph nodes, tendons, colon, and appendix, were collected and used for the molecular identification of Mycobacterium species and analysis of cytokine mRNA expression. Results: IFN-γ, TNF-α, IP-10, CXCL9, CXCL11, and GM-CSF mRNA expression levels in MTB-infected tissues were significantly higher than those in uninfected samples. Additionally, the differences in the mRNA expression levels of IFN-γ, CXCL9, and GM-CSF between MTB-infected and uninfected tissues were statistically significant were statistically significant (p < 0.05). Correlation curve analysis indicated that the mRNA expression of IFN-γ was inversely proportional to that of IP-10 and that the mRNA expression levels of IFN-γ, TNF-α, CXCL9, CXCL11, GM-CSF, and TNFR were proportional and well-correlated. Furthermore, to establish marker profiles for detecting MTB infection, the statistically significant expression levels of three markers were combined. We confirmed that the combined profile of IFN-γ, CXCL9, and GM-CSF expression levels was statistically significant (P < 0.001). Conclusions: Although the mRNA expression patterns of host immune markers may vary according to MTB infection status, these patterns may be highly correlated and can be simultaneously used as an additional indicator for diagnosing TB in human tissue samples.

Background Meniscal tears are commonly observed in patients with knee osteoarthritis (OA), however, clinical significance of such lesions detected by magnetic resonance imaging is in many cases unclear. This study aimed to determine the clinical effectiveness of arthroscopic partial meniscectomy (APM) compared with non-operative care in patients with knee OA. Method We used existing systematic reviews with updates of latest studies. Three randomized controlled studies were selected, where two studies compared the effects of APM plus physical therapy (PT) with PT alone and one compared APM alone and PT alone. While 1 study exclusively included OA patients, 2 studies included 21.1 and 12% of patients with no radiographic OA. Patients with knee locking were unanimously excluded. Results Upon comparison of APM plus PT and PT alone, there was no significant difference observed in knee function, physical activity, or adverse events. Knee pain was observed to be significantly lower in the APM plus PT group at 6 months, but there was no difference between the two groups at 12 and 24 months. With respect to the comparison between APM alone and PT alone, PT was non-inferior based on the criteria for knee function during 24 months; however, knee pain was significantly reduced in the APM alone group. Conclusions Our study showed that knee pain was significantly improved in the APM group compared to non-operative care group at 6 months and over 24 months. Our result was based on only 3 randomized controlled trials (RCTs) revealing a significant knowledge gap, hence demanding more high-quality RCTs in OA patients. Trial Registration PROSPERO Identifier: CRD42020215965, Graphical Abstract

This study was conducted to evaluate seasonal groundwater quality due to groundwater pumping and hydrochemical characteristics with groundwater level fluctuations in an agricultural area in Korea. Groundwater levels were observed for about one year using automatic monitoring sensors, and groundwater uses were estimated based on the monitoring data. Groundwater use in the area is closely related to irrigation for rice farming, and rising groundwater levels occur during the pumping, which may be caused by the irrigation water of rice paddies. Hydrochemical analysis results for two separate times (17 July and 1 October 2019) show that the dissolved components in groundwater decreased overall due to dilution, especially at wells in the alluvial aquifer and shallow depth. More than 50% of the samples were classified as CaHCO3 water type, and changes in water type occurred depending on the well location. Water quality changes were small at most wells, but changes at some wells were evident. In addition, the groundwater quality was confirmed to have the effect of saltwater supplied during the 2018 drought by comparison with seawater. According to principal component analysis (PCA), the water quality from July to October was confirmed to have changed due to dilution, and the effect was strong at shallow wells. In the study areas where rice paddy farming is active in summer, irrigation water may be one of the important factors changing the groundwater quality. These results provide a qualitative and quantitative basis for groundwater quality change in agricultural areas, particularly rice paddies areas, along with groundwater level and usage.

Cigarette smoke is a highly complex mixture of nicotine and non-nicotine constituents. Exposure to cigarette smoke enhances tobacco dependence by potentiating glutamatergic neurotransmission via stimulation of nicotinic acetylcholine receptors (nAChRs). We investigated the effects of nicotine and non-nicotine alkaloids in the cigarette smoke condensates extracted from two commercial cigarette brands in South Korea (KCSC A and KCSC B) on psychomotor behaviors and glutamate levels in the dorsal striatum. Repeated and challenge administration of KCSCs (nicotine content: 0.4 mg/kg, subcutaneous) increased psychomotor behaviors (ambulatory, rearing, and rotational activities) and time spent in psychoactive behavioral states compared to exposure to nicotine (0.4 mg/kg) alone. The increase in psychomotor behaviors lasted longer when exposed to repeated and challenge administration of KCSCs compared to nicotine alone. In parallel with sustained increase in psychomotor behaviors, repeated administration of KCSCs also caused long-lasting glutamate release in the dorsal striatum compared to nicotine alone. KCSC-induced changes in psychomotor behaviors and glutamate levels in the dorsal striatum were found to be strongly correlated. These findings suggest that non-nicotine alkaloids in commercial cigarette smoke synergistically act with nicotine on nAChRs, thereby upregulating glutamatergic response in the dorsal striatum, which contributes to the hypersensitization of psychomotor behaviors.

Antimicrobial air filters are required to protect humans from the risk of secondary bioaerosol pollution as well as airborne particles. Three plant extracts (tea-tree oil, rosemary, and garlic) were selected to replace antimicrobial chemicals in air filters. The antimicrobial activity of plant extracts was investigated using Micrococcus luteus and Escherichia coli. Phytochemicals present in the three plant extracts were identified using a gas chromatograph coupled with a mass spectrometer. The extracts were spray-coated on polyethylene terephthalate filter surfaces using silicate polymeric coating and evaluated via X-ray photoelectron spectroscopy and a scanning electron microscope with energy dispersive spectroscopy. After coating, an increase of 9.1% in the pressure drop was observed. The strain Micrococcus luteus was used to evaluate the antimicrobial activity of the air filter. After bioaerosol exposure, the tea-tree oil-coated filters immediately induced M. luteus cell inactivation (40&ndash, 55%), whereas the rosemary and garlic coated filters did not. However, 48 h after exposure, a significant M. luteus inactivation of 99.99%, 99.0%, and 99.9% was recorded for concentrations of 2.89, 6.73, and 11.51 mg/cm2 for the tea-tree, rosemary, and garlic extracts, respectively. The coated filters exhibited high antimicrobial activity, thereby indicating significant potential for application as self-cleaning air filters.

The FeSe nematic phase has been the focus of recent research on iron-based superconductors (IBSs) due to its unusual properties, which are distinct from those of the pnictides. A series of theoretical/experimental studies were performed to determine the origin of the nematic phase. However, they yielded conflicting results and caused additional controversies. Here, we report the results of angle-resolved photoemission and X-ray absorption spectroscopy studies on FeSe detwinned by a piezo stack. We fully resolved band dispersions with orbital characters near the Brillouin zone (BZ) corner, and revealed an absence of any Fermi pocket at the Y point in the 1-Fe BZ. In addition, the occupation imbalance between $${d}_{{xz}}$$ d x z and $${d}_{{yz}}$$ d y z orbitals was the opposite of that of iron pnictides, consistent with the identified band characters. These results resolve issues associated with the FeSe nematic phase and shed light on the origin of the nematic phase in IBSs.

We evaluated the effect of 13.56 MHz modulated electro-hyperthermia (mEHT) boost in neoadjuvant treatment for cT3-4- or cN-positive rectal cancer. Sixty patients who completed the mEHT feasibility trial (ClinicalTrials.gov Identifier: NCT02546596) were analyzed. Whole pelvis radiotherapy of 40 Gy, mEHT boost twice a week during radiotherapy, and surgical resection 6–8 weeks following radiotherapy were performed. The median age was 59. The median follow-up period was 58 (6–85) months. Total/near total tumor regression was observed in 20 patients (33.3%), including nine cases of complete response. T- and N-downstaging was identified in 40 (66.6%) and 53 (88.3%) patients, respectively. The 5-year overall and disease-free survival were 94.0% and 77.1%, respectively. mEHT energy of ≥3800 kJ potentially increased the overall survival (p = 0.039). The ypN-stage and perineural invasion were possible significant factors in disease-free (p = 0.003 and p = 0.005, respectively) and distant metastasis-free (p = 0.011 and p = 0.034, respectively) survival. Tumor regression, resection margin status, and other molecular genetic factors showed no correlation with survival. Although a limited analysis of a small number of patients, mEHT was feasible considering long-term survival. A relatively low dose irradiation (40 Gy) plus mEHT setting could ensure comparable clinical outcomes with possible mEHT-related prognostic features.

Bacterial infections and the formation of biofilms on the surface of implantable medical devices are critical issues that cause device failure. Implantable medical devices, such as drug delivery technologies, offer promising benefits for targeted and prolonged drug release, but a number of common disadvantages arise that include inadequate release and side effects. Organic film coatings for antifouling and drug delivery are expected to overcome these challenges. Ferrocene polymer-based multifunctional multilayer films were prepared to control the reactive oxygen species (ROS)-responsive release of therapeutic agents while maintaining an antifouling effect and improving biocompatibility. Polymers based on ferrocene and polyethylene glycol were prepared by controlling the molar ratio of carboxylate and amine groups. Layer-by-layer deposition was optimized to achieve the linear growth and self-assembly of dense and stable films. Outstanding anti-biofilm activity (~91% decrease) could be achieved and the films were found to be blood compatible. Importantly, the films effectively incorporated hydrophobic drugs and exhibited dual-responsive drug release at low pH and under ROS conditions at physiological pH. Drug delivery to MCF-7 breast cancer cells was achieved using a Paclitaxel loaded film, which exhibited an anticancer efficacy of 62%. STATEMENT OF SIGNIFICANCE: Healthcare associated infection is caused by the formation of a biofilm by bacteria on the surface of a medical device. In order to solve this, extensive research has been conducted on many coating technologies. Also, a method of chemical treatment by releasing the drug when it enters the body by loading the drug into the coating film is being studied. However, there is still a lack of technology that can achieve both functions of preventing biofilm production and drug delivery. Therefore, in this study, a multilayer thin film that supports drug and inhibits biofilm formation was prepared through Layer-by-Layer coating of a polymer containing PEG to prevent adsorption. As such, it helps the design of multifunctional coatings for implantable medical devices.

CT-P10 is the first biosimilar of rituximab (RTX) for the treatment of rheumatoid arthritis (RA). The application of valuable biosimilar for the treatment of RA may decrease economic burden of society, and disease activity of RA. Thus, it is worthwhile to identify the economic advantage and further requirement for the proper use of CT-P10 in real world.Literature searching was performed to identify suitable references written in English for this review article. Rituximab, biosimilar, CT-P10, and rheumatoid arthritis were used as keywords. Current state of RA treatment, position of RTX in the recommendations for the treatment of RA, current status of RTX biosimilar development were assessed before evaluating CT-P10 itself. Physicochemical property, pharmacokinetic profile through phase I to phase III studies, pharmacodynamics, toxicology data, clinical efficacy, and safety were reviewed.As the first biosimilar to originator RTX, CT-P10 may be a useful alternative for the treatment of RA in all indications for originator RTX. In addition, more studies are required to identify long-term effectiveness and safety of CT-P10 in real world. It is also important to find out new indications of CT-P10 and effective mechanisms to lessen nocebo effect against biosimilar including CT-P10.

Suppression of pathogenic bacterial growth to increase food and agricultural productivity is important. We previously developed novel hexapeptides (KCM12 and KCM21) with antimicrobial activities against various phytopathogenic bacteria and N2 plasma-treated buffer (NPB) as an alternative method for bacterial inactivation and as an antibiofilm agent of crops. Here, we developed an enhanced antibiofilm method based on antimicrobial hexapeptides with N2 plasma-treated buffer against plant pathogens. Our results demonstrated that hexapeptides effectively inhibited the growth of Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) and the biofilm it formed. Potent biofilm formation-inhibiting effects of hexapeptides were observed at concentrations of above 20 &micro, M, and samples treated with hexapeptide above 100 &micro, M reduced the ability of the bacteria to produce biofilm by 80%. 3D confocal laser scanning microscopy imaging data revealed that the antimicrobial activity of hexapeptides was enough to affect the cells embedded inside the biofilm. Finally, combination treatment with NPB and antimicrobial hexapeptides increased the antibiofilm effect compared with the effect of single processing against multilayered plant pathogen biofilms. These findings show that the combination of hexapeptides and NPB can be potentially applied for improving crop production.

Aptides, developed by our laboratory, are a novel class of high-affinity peptides. Here, we describe the conjugation of an aptide targeting extra-domain B (EDB) of tumor-associated fibronectin to drug-containing liposomes and explore the potential of these aptide-conjugated liposomes as a robust and efficient targeted drug-delivery system for glioma therapy.

The Shockley–Queisser (SQ) limit provides a convenient metric for predicting light-to-electricity conversion efficiency of a solar cell based on the band gap of the light-absorbing layer. In reality, few materials approach this radiative limit. We develop a formalism and computational method to predict the maximum photovoltaic efficiency of imperfect crystals from first principles. The trap-limited conversion efficiency includes equilibrium populations of native defects, their carrier-capture coefficients, and the associated recombination rates. When applied to kesterite solar cells, we reveal an intrinsic limit of 20% for Cu2ZnSnSe4, which falls far below the SQ limit of 32%. The effects of atomic substitution and extrinsic doping are studied, leading to pathways for an enhanced efficiency of 31%. This approach can be applied to support targeted-materials selection for future solar-energy technologies.

In this paper, we propose an intrusion detection system based on the estimation of the R&eacute, nyi entropy with multiple orders. The R&eacute, nyi entropy is a generalized notion of entropy that includes the Shannon entropy and the min-entropy as special cases. In 2018, Kim proposed an efficient estimation method for the R&eacute, nyi entropy with an arbitrary real order &alpha, In this work, we utilize this method to construct a multiple order, R&eacute, nyi entropy based intrusion detection system (IDS) for vehicular systems with various network connections. The proposed method estimates the R&eacute, nyi entropies simultaneously with three distinct orders, two, three, and four, based on the controller area network (CAN)-IDs of consecutively generated frames. The collected frames are split into blocks with a fixed number of frames, and the entropies are evaluated based on these blocks. For a more accurate estimation against each type of attack, we also propose a retrospective sliding window method for decision of attacks based on the estimated entropies. For fair comparison, we utilized the CAN-ID attack data set generated by a research team from Korea University. Our results show that the proposed method can show the false negative and positive errors of less than 1% simultaneously.

Suppose one aims to identify only the top- $K$ among a large collection of $n$ items provided $M$ -wise comparison data, where a set of $M$ items in each data sample are ranked in order of individual preference. Natural questions that arise are as follows: 1) how one can reliably achieve the top- $K$ rank aggregation task; and 2) how many $M$ -wise samples one needs to achieve it. In this paper, we answer these two questions. First, we devise an algorithm that effectively converts $M$ -wise samples into pairwise ones and employs a spectral method using the refined data. Second, we consider the Plackett–Luce (PL) model, a well-established statistical model, and characterize the minimal number of $M$ -wise samples (i.e., sample complexity) required for reliable top- $K$ ranking. It turns out to be inversely proportional to $M$ . To characterize it, we derive a lower bound on the sample complexity and prove that our algorithm achieves the bound. Moreover, we conduct extensive numerical experiments to demonstrate that our algorithm not only attains the fundamental limit under the PL model but also provides robust ranking performance for a variety of applications that may not precisely fit the model. We corroborate our theoretical result using synthetic datasets, confirming that the sample complexity decreases at the rate of $\frac{1}{M}$ . Also, we verify the applicability of our algorithm in practice, showing that it performs well on various real-world datasets.

Purpose We describe the daily bladder volume change observed by mega-voltage computed tomography (MVCT) during pelvic radiotherapy with potential predictors of increased bladder volume variations. Materials and Methods For 41 patients who received pelvic area irradiation, the volumes of bladder and pelvic body contour were measured twice a day with pre- and post-irradiation MVCT from the 1st to the 10th fraction. The median prescription dose was 20 Gy (range, 18 to 30 Gy) up to a 10th fraction. The upper and lower margin of MVCT scanning was consistent during the daily treatments. The median age was 69 years (range, 33 to 86 years) and 10 patients (24.4%) were treated postoperatively. Results Overall bladder volume on planning computed tomography was 139.7 ± 92.8 mL. Generally, post-irradiation bladder volume (POSTBV) was larger than pre-irradiation bladder volume (PREBV) (p < 0.001). The mean PREBV and POSTBV was reduced after 10 fraction treatments by 21.3% (p = 0.028) and 25.4% (p = 0.007), respectively. The MVCT-scanned body contour volumes had a tendency to decrease as the treatment sessions progressed (p = 0.043 at the 8th fraction and p = 0.044 at the 10th fraction). There was a statistically significant correlation between bladder filling time and PREBV (p = 0.001). Conclusion Daily MVCT-based bladder volume assessment was feasible both intra- and inter-fractionally.