Ginsenoside Rg3 targets glycosylation of PD-L1 to enhance anti-tumor immunity in non-small cell lung cancer.

Background: Reactivate the T cell immunity by PD-1/PD-L1 checkpoint blockade is widely used in non-small cell lung cancer (NSCLC) patients, while the post-translational modification of Programmed death ligand-1 (PD-L1) is commonly existed in various cancer cells, thus increases the complexity and difficulty in therapy development. Ginsenoside Rg3 is an active component of traditional Chinese herb Ginseng with multiple pharmacological effects including immune regulation. However, the effect on the glycosylation of PD-L1 is unknown. Methods: NSCLC cell lines were tested for glycosylation of PD-L1, and the potential mechanisms were investigated. Tumor cell-T cell coculture experiment was conducted and the activation of T cells and cytotoxicity were measured by flow cytometry. In vivo xenograft mouse tumor model was used to investigate the effects of Rg3 on PD-L1-mediated immunosuppression and tumor growth. Results: Here, we identified PD-L1 is widely N-linked glycosylated in NSCLC cell lines, while Rg3 could inhibit the glycosylation of PD-L1 by downregulating the EGFR signaling and further activate GSK3b-mediated degradation, thus resulted in reduced PD-L1 expression. Moreover, the inhibition of PD-L1 glycosylation promoted the activation and cytotoxicity of T cells under coculture condition. In addition, Rg3 could decrease the tumor volume and enhance anti-tumor T cell immunity as evidence by the upregulated expression of Granzyme B and perforin in CD8+T cells, along with elevated serum IL-2, IFN-g and TNF-a level in Rg3-treated mice. Conclusions: These results suggest that Rg3 inhibits PD-L1 glycosylation and thus enhance anti-tumor immunity, which provide new therapeutic insight into drug discovery.

Sensorimotor Processing in Elite and Sub-Elite Adolescent Sprinters during Sprint Starts: An Electrophysiological Study.

Most studies on sprint performance have focused on kinematics and kinetics of the musculoskeletal system for adults, with little research on the central sensorimotor transmission and processes, especially for adolescent sprinters. This study aimed to determine whether differences in the integrity of the central auditory system and audiomotor transmissions between the elite and sub-elite adolescent sprinters may affect their performance in the 100 m time. Twenty-nine adolescent junior high school students, including elite national-class and sub-elite regional-class athletes, were assessed. Visual and auditory evoked potentials (VEP and AEP) as well as electroencephalography (EEG) and electromyography (EMG) were recorded and analyzed during a sprint start. The electrophysiological results clearly reveal differences in central auditory transmission between elite and sub-elite groups, and between sexes. There were significant differences between elite and sub-elite groups, and during a sprint start, the EEG activities for elite female and male athletes showed significant time-dependent differences in peak amplitudes following the three auditory cues (ready, set, and gunshot). These findings can provide coaches with a more comprehensive consideration for sports-specific selection based on the athletes' individual conditions, e.g., sensorimotor neuroplastic training for providing precise and efficient training methods to improve young sprinters' performance.

Stereochemical Control of Redox CoII/CoIII-Cages with Switchable Cotton Effects Based on Labile-Static States.

The structural dynamics of artificial assemblies, in aspects such as molecular recognition and structural transformation, provide us with a blueprint to achieve bioinspired applications. Here, we describe the assembly of redox-switchable chiral metal-organic cages Λ8/Δ8-[Pd6(CoIIL3)8]28+ and Λ8/Δ8-[Pd6(CoIIIL3)8]36+. These isomeric cages demonstrate an on-off chirality logic gate controlled by their chemical and stereostructural dynamics tunable through redox transitions between the labile CoII-state and static CoIII-state with a distinct Cotton effect. The transition between different states is enabled by a reversible redox process and chiral recognition originating in the tris-chelate Co-centers. All cages in two states are thoroughly characterized by NMR, ESI-MS, CV, CD, and X-ray crystallographic analysis, which clarify their redox-switching behaviors upon chemical reduction/oxidation. The stereochemical lability of the CoII-center endows the Λ8/Δ8-CoII-cages with efficient chiral-induction by enantiomeric guests, leading to enantiomeric isomerization to switch between Λ8/Δ8-CoII-cages, which can be stabilized by oxidation to their chemically inert forms of Λ8/Δ8-CoIII-cages. Kinetic studies reveal that the isomerization rate of the Δ8-CoIII-cage is at least an order of magnitude slower than that of the Δ8-CoII-cage even at an elevated temperature, while its activation energy is 16 kcal mol-1 higher than that of the CoII-cage.

Taxonomic study on the genus Mongoloniscus Verhoeff, 1930 (Isopoda, Agnaridae) from China: morphological and phylogenetic analyses.

A combination of morphological traits and DNA data (COI and 28S rRNA partial sequences) was used to study the genus Mongoloniscus Verhoeff, 1930 from China. Four new species are described: M.crenatus Jiang, Li & Huang, sp. nov., M.orientalis Jiang, Li & Huang, sp. nov., M.polyacanthum Jiang, Li & Huang, sp. nov., and M.parvus Jiang, Li & Huang, sp. nov. Following an in-depth examination of the Mongoloniscus species, Lucasioidesvannamei (Arcangeli, 1927), comb. nov. (from Mongoloniscus) is proposed, and M.chevronus Yang & An, 2021, syn. nov. is synonymized with Koreoniscusracovitzai (Arcangeli, 1927). A restrictive criterion for recognizing the genus Mongoloniscus is also provided in the present study.

A Two-Step Fluorescence-Resonance Energy Transfer System Constructed by Platinum(II) Metallacycle Based Molecular Recognition.

Considerable progress in the construction of efficient fluorescence-resonance energy transfer (FRET) systems has promoted the development of artificial energy transfer materials. However, despite recent advances, the exploration of efficient and easy strategies to fabricate novel supramolecular systems with FRET activities is still a challenge. Here, we report that a two-step FRET system was successfully achieved, driven by platinum metallacycle based host-guest interactions. The two-step FRET system is used for the preparation of a white-light-emitting diode and serves as a nanoreactor for the photosynthetic process. This work offers a strategy for the fabrication of FRET systems and opens opportunities for functional materials constructed by platinum(II) metallacycle based host-guest interactions.

SLCO4A1-AS1 regulates laryngeal squamous cell carcinoma cell phenotypes via the Wnt pathway.

AIM: Long non-coding RNAs were widely reported to regulate laryngeal squamous cell carcinoma (LSCC), a prevalent tumor in the head and neck. We aimed to investigate the role of solute carrier organic anion transporter family member 4A1 antisense RNA 1 (SLCO4A1-AS1) in LSCC. MATERIALS & METHODS: CCK-8 and colony formation assays were conducted to examine the viability and proliferation of LSCC cells. The apoptosis of LSCC cells was evaluated using flow cytometry and TUNEL assays. The distribution of SLCO4A1-AS1 in LSCC cells was detected by subcellular fractionation assay. The interaction between molecules was confirmed using luciferase reporter assay. RESULTS: SLCO4A1-AS1 was overexpressed in LSCC tissues and cells. Furthermore, silenced SLCO4A1-AS1 repressed the proliferation and facilitated apoptosis of LSCC cells. Mechanistical investigation revealed that SLCO4A1-AS1 was a competing endogenous RNA (ceRNA) to upregulate SETD7 by binding with miR-7855-p. Additionally, SLCO4A1-AS1 positively regulated the Wnt/ß-catenin signaling pathway by upregulating SETD7. Rescue experiments demonstrated that SLCO4A1-AS1 promoted LSCC proliferation and inhibited LSCC apoptosis by upregulation of SETD7 and activation of the Wnt/ß-catenin pathway. CONCLUSION: SLCO4A1-AS1 promotes proliferation and inhibits apoptosis of LSCC cells by upregulation of SETD7 in a miR-7855-5p dependent way to activate the Wnt/ß-catenin pathway.

First record of the subgenus Hemilepistus (Desertellio) (Isopoda, Agnaridae) from China.

The subgenus Hemilepistus (Desertellio) Verhoeff, 1930 is reported from China for the first time. A new species of the subgenus, H. (D.) gracilentus Li & Jiang sp. nov., is described from Xinjiang Uygur Autonomous Region, northwestern China and H. (D.) ruderalis (Pallas, 1771) is redescribed as a new record for Chinese Fauna, and its polymorphism is verified by using the COI sequences. A key to the worldwide species of the subgenus is provided.

Fluorinated leaning pillar[6]arene: synthesis, structure and selective iodide anion binding by anion-π interactions.

Anion recognition has continuously attracted significant attention due to its important role in environmental and biological sciences. Here, we have designed and synthesized an electron-deficient fluorinated leaning pillar[6]arene 1 that contains two tetrafluoro-benzene units. The electron-deficient fluorinated leaning pillar[6]arene 1 is capable of selectively recognizing iodide anions to form a host-guest complex with 1 : 1 stoichiometry driven by anion-π interactions. Our work ascribes this selective recognition to the preorganization of macrocycles, suitable cavity size, and the effect of anion-π interactions. The innovative application of this macrocycle offers us a new avenue for the design of selective receptors for anions and electron-deficient macrocyclic arenes.

A third species of Parakermania Vandel, 1973 (Isopoda: Oniscidea: Armadillidae) from China.

Parakermania longa sp. nov., the third species of the woodlouse genus Parakermania Vandel, 1973 is described and illustrated from China. The new species differs from the other two congeners in having a different number of dorsal tubercles, and two well-developed ornamentations on the outer sides of the sixth pereonite going beyond the apex of telson. A key to Parakermania species is provided.

Detection of Aliphatic Aldehydes by a Pillar[5]arene-based Fluorescent Supramolecular Polymer with Vaporchromic Behavior.

The detection of volatile aliphatic aldehydes is of significance because of their chemical toxicity, physical volatility and widespread applications in chemical industrial processes. In this work, the direct detection of aliphatic aldehydes is tackled using a pillar[5]arene-based fluorescent supramolecular polymer with vaporchromic behavior. Thin films with strong orange-yellow fluorescence are prepared by coating the linear supramolecular polymer on glass sheets. When the thin films are exposed to aliphatic aldehydes with different carbon chain lengths, they can selectively sensing n-butyraldehyde (C4 ) and caprylicaldehyde (C8 ), accompanied by fluorescence quenching, indicating that the supramolecular polymer is a highly selective vapochromic response material for aliphatic aldehydes with long alkyl chains.

Integrative taxonomy on the rare sky-island Ligidium species from southwest China (Isopoda, Oniscidea, Ligiidae).

BACKGROUND: The sky-island Ligidium species fauna in southwest China is poorly known. Before this study, six of the seven sky-island species of the genus were known to be endemic to southwest China. In morphology, Ligidium species are often difficult to identify, and an appraisal of integrative taxonomy is needed. RESULTS: We integrated morphology and molecular analyses to delimit Ligidium species. Molecular species delimitation based on distance- and evolutionary models recovered seven-candidate lineages from five gene markers (COI, 12S rRNA, 18S rRNA, 28S rRNA and NAK). We also estimated that the species divergences of sky-island Ligidium in southwest China started in late Eocene (40.97 Mya) to middle Miocene (15.19 Mya). Four new species (L. duospinatum Li, sp. nov., L. acuminatum Li, sp. nov., L. rotundum Li, sp. nov. and L. tridentatum Li, sp. nov.) are described. Morphological confusion among L. denticulatum Shen, 1949, L. inerme Nunomura & Xie, 2000 and L. sichuanense Nunomura, 2002 is clarified by integrative taxonomy. CONCLUSION: This work confirms that an integrative approach to Ligidium taxonomy is fundamental for objective classification, and deduced the uplift of Qinghai-Tibetan Plateau in the late Eocene and middle Miocene as one of the principal reasons for the species divergences of sky-island Ligidium in southwest China. We also inferred that sky-island mountains have a huge reserve of higher Ligidium species diversity.

First record of the genus Hemilepistus (Isopoda: Agnaridae) from China, with description of two new species.

The genus Hemilepistus Budde-Lund, 1879 is reported from China for the first time. Two new species of the subgenus H. (Hemilepistus) are described from Xinjiang Uygur Autonomous Region, northwest China: H. (H.) dushengi sp. nov. and H. (H.) conicus sp. nov. A key to the worldwide species of the subgenus is provided.

Effect and mechanism of BDNF/TrkB signaling on vestibular compensation.

Brain-derived neurotrophic factor (BDNF) regulates neuronal plasticity by targeting the tyrosine kinase B receptor (TrkB) receptor, but limited researches concentrate on the role of BDNF/TrkB signaling in vestibular compensation. In this study, rats with unilateral vestibular dysfunction were established by unilateral labyrinthectomy (UL) and infusion with siBDNF or 7, 8-Dihydroxyflavone (7,8-DHF, a TrkB receptor agonist). The behavioral scores of rats with vestibular deficits were determined and the rotarod test was performed after UL. BDNF and TrkB levels after UL were determined by western blot and quantitative reverse transcription PCR (qRT-PCR). 5-bromo-2'-deoxyuridine (BrdU)-positive cells (newly generated cells) and GAD67-positive cells (GABAergic neurons) were identified by immunohistochemistry. Glial fibrillary acidic protein (GFAP) (astrocyte marker)-positive cells were identified and GABA type A receptor (GABAAR) expression was detected by immunofluorescence. We found that after UL, BDNF and TrkB levels were up-regulated with a maximum value at 4 h, and then progressively down-regulated during 4 h ~ 7 d. Blocking BDNF/TrkB signaling inhibited the recovery from vestibular deficits, decreased the numbers of newly generated cells and astrocytes in medial vestibular nucleus (MVN), inferior vestibular nerve (IVN), superior vestibular nerve (SVN) and lateral vestibular nucleus (LVN), and disrupted the balances of GABAergic neurons and GABAAR expressions in the left (lesioned) side and right (intact) side of MVN, whereas activation of BDNF/TrkB signaling caused opposite results. The current study indicated that BDNF/TrkB signaling avails vestibular compensation, depending on the number of newly generated cells and astrocytes, the rebalance of GABAergic neurons, and GABAAR expression in bilateral MVN.

Integrative taxonomy reveals a new species of the genus Burmoniscus (Isopoda, Philosciidae) from the Xuefeng Mountains, China.

Three species of the genus Burmoniscus are identified from the Xuefeng Mountains, central China, by integrating morphological and molecular approaches. Burmoniscuschuanyanensis Li, sp. nov. is described. Morphological photographs of the new species are provided.

Efficacy of High-Flow Nasal Cannula Oxygen Therapy in Patients with Mild Hypercapnia.

OBJECTIVES: To investigate the indications of high-flow nasal cannula (HFNC) oxygen therapy among patients with mild hypercapnia and to explore the predictors of intubation when HFNC fails. METHODS: This retrospective study was conducted based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Adult patients with mild hypercapnia (45 < PaCO2 ≤ 60 mmHg) received either HFNC or non-invasive ventilation (NIV) oxygen therapy. Propensity score matching (PSM) was implemented to increase between-group comparability. The Kaplan-Meier method was used to estimate overall survival and cumulative intubation rates, while 28-day mortality and 48-h and 28-day intubation rates were compared using the Chi-squared test. The predictive performances of HR/SpO2 and the ROX index (the ratio of SpO2/FiO2 to respiratory rate) at 4 h were assessed regarding HFNC failure, which was determined if intubation was given within 48 h after the initiation of oxygen therapy. The area under the receiver operating characteristic curve (AUC) for HR/SpO2 and the ROX index were calculated and compared. RESULTS: A total of 524,520 inpatient hospitalization records were screened, 106 patients in HFNC group and 106 patients in NIV group were successfully matched. No significant difference in 48-h intubation rate between the HFNC group (the treatment group) and the NIV group (the control group) (14.2% vs. 8.5%, p = 0.278); patients receiving HFNC had higher 28-day intubation rate (26.4% vs. 14.2%, p = 0.029), higher 28-day mortality (17.9% vs. 8.5%, p = 0.043), and longer ICU length of stay (4.4 vs. 3.3 days, p = 0.019), compared to those of NIV group. The AUC of HR/SpO2 at 4 h after the initiation of HFNC yielded around 0.660 for predicting 48-h intubation, greater than that of the ROX index with an AUC of 0.589 (p < 0.01). CONCLUSION: Patients with impending respiratory failure had lower intubation rate, shorter ICU length of stay, and lower mortality when treated mild hypercapnia with NIV over HFNC. As opposed to the ROX index, a modest, yet improved predictive performance is demonstrated using HR/SpO2 in predicting the failure of HFNC among these patients.

Immunotherapy-Associated Pancreatic Adverse Events: Current Understanding of Their Mechanism, Diagnosis, and Management.

Immune checkpoint inhibitors (ICIs) such as anti-programmed death-1 (PD-1) and its ligand PD-L1 and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibodies, are involved in T cell-mediated immune response augmentation and promote anti-tumor immunity. Cancer patients treated with combination of immunotherapy, chemotherapy, radiotherapy, and targeted therapy exhibit superior clinical outcomes and tolerance compared with patients treated with monotherapies. However, immutherapy is associated with several concomitant immune-related adverse events (irAEs). For instance, IrAEs interferes with function of gastrointestinal tract, endocrine, dermatological, nervous system and musculoskeletal systems. ICIs-associated pancreatic injury might causes decrease in endocrine and exocrine pancreatic function, resulting in metabolic and nutritional disorders. Clinicians who administer immune checkpoint inhibitors to cancer patients are diagnosed with hyperglycemia, abdominal pain and steatorrhea. Currently, the precise mechanism of ICIs-associated pancreatic injury has not been fully explored. This paper summarizes incidence, diagnosis, clinical characteristics, potential mechanisms, and treatment management patterns of ICIs-associated pancreatic AEs based on previous studies. In addition, possible management approaches of these adverse effects are presented in this paper. in the findings summarized in this paper lay a basis for management of ICIs-associated pancreatic AEs and expanding future immunotherapy applications.

[Impact of post-thoracotomy analgesia with dexmedetomidine and morphine on immunocytes: a randomized clinical trial]. / Impacto da analgesia pós­toracotomia com dexmedetomidina e morfina em imunócitos: estudo randomizado.

OBJECTIVE: This study aimed to investigate the impact of post-thoracotomy analgesia with dexmedetomidine and morphine on immunocytes. METHODS: A total of 118 patients with post-thoracotomy Patient-Controlled Intravenous Analgesia (PCIA) in our hospital from March 2016 to July 2018 were randomly selected and divided into the Composite (COM) Group (57 patients administered with dexmedetomidine [1.0 µg.kg-1 body weight] and morphine [0.48 mg.kg-1 body weight]) and the Morphine (MOR) Group (61 patients administered with morphine [0.48 mg.kg-1]). The values of lymphocyte subsets (CD3+, CD4+, and CD8+) and Natural Killer cells in the peripheral blood of these two groups were detected by FACSCalibur flow cytometry at different time points (before anesthesia induction [T0], immediately after tracheal extubation [T1], 12 hours after surgery [T2], 24 hours after surgery [T3], 48 hours after surgery [T4], 72 hours after surgery [T5], and 7 days after surgery [T6]). The doses of morphine at T3 to T5 and the adverse reactions between the two groups were also recorded and compared. RESULTS: The CD3+ level and the CD4+/CD8+ ratio at T2 to T5 and the CD4+ level and NK cells at T3 to T5 were significantly higher in the COM Group than in the MOR Group (p < 0.05). The postoperative morphine dose and the incidence of postoperative itching, nausea, and vomiting were significantly lower in the COM Group than in the MOR Group (p < 0.05). CONCLUSIONS: Dexmedetomidine combined with morphine for post-thoracotomy PCIA can improve the function of immunocytes, reduce morphine consumption, and reduce the adverse reactions during analgesia induction.

First record of the genus Tetracona Meyrick (Lepidoptera, Crambidae) from China, with description of a new species.

The genus Tetracona has two species with an Australian distribution. The present study aims to record the genus from China for the first time and to add a third species, T. multispina Jie & Li, sp. nov. to the genus. The new species can be distinguished from the congeners by the antemedial line connecting the postmedial line near the dorsum in the hindwing, and the phallus with a cluster of spine-like cornuti in the male genitalia. Images of the habitus, tympanal organs and male genitalia are provided for the new species.

Impact of post-thoracotomy analgesia with dexmedetomidine and morphine on immunocytes: a randomized clinical trial / Impacto da analgesia pós-toracotomia com dexmedetomidina e morfina em imunócitos: estudo randomizado

Abstract Objective This study aimed to investigate the impact of post-thoracotomy analgesia with dexmedetomidine and morphine on immunocytes. Methods A total of 118 patients with post-thoracotomy Patient-Controlled Intravenous Analgesia (PCIA) in our hospital from March 2016 to July 2018 were randomly selected and divided into the Composite (COM) Group (57 patients administered with dexmedetomidine [1.0 µg.kg-1 body weight] and morphine [0.48 mg.kg-1 body weight]) and the Morphine (MOR) group (61 patients administered with morphine [0.48 mg.kg-1]). The values of lymphocyte subsets (CD3+, CD4+, and CD8+) and Natural Killer cells in the peripheral blood of these two groups were detected by FACSCalibur flow cytometry at different time points (before anesthesia induction [T0], immediately after tracheal extubation [T1], 12 hours after surgery [T2], 24 hours after surgery [T3], 48 hours after surgery [T4], 72 hours after surgery [T5], and 7 days after surgery [T6]). The doses of morphine at T3 to T5 and the adverse reactions between the two groups were also recorded and compared. Results The CD3+ level and the CD4+/CD8+ ratio at T2 to T5 and the CD4+ level and NK cells at T3 to T5 were significantly higher in the COM Group than in the MOR Group (p< 0.05). The postoperative morphine dose and the incidence of postoperative itching, nausea, and vomiting were significantly lower in the COM Group than in the MOR Group (p< 0.05). Conclusions Dexmedetomidine combined with morphine for post-thoracotomy PCIA can improve the function of immunocytes, reduce morphine consumption, and reduce the adverse reactions during analgesia induction.

Resumo Objetivo Estudar o impacto em linfócitos causado pelo uso da dexmedetomidina associada à morfina para analgesia pós-toracotomia. Método Um total de 118 pacientes utilizando Analgesia Intravenosa Controlada pelo Paciente (AICP) pós-toracotomia em nosso hospital, de março de 2016 a julho de 2018, foram selecionados aleatoriamente e divididos em dois grupos: o Grupo Combinado [COM, 57 pacientes que receberam dexmedetomidina (1,0 µg.kg-1 de peso corpóreo) associada à morfina (0,48 mg.kg-1 de peso corpóreo)] e o Grupo Morfina [MOR, 61 pacientes, que receberam somente morfina (0,48 mg.kg-)]. Os valores dos subconjuntos de linfócitos (CD3+, CD4+ e CD8+) e das células NK no sangue periférico desses dois grupos foram medidos por citometria de fluxo FACSCalibur em diferentes momentos do estudo [antes da indução anestésica (T0), imediatamente após extubação traqueal (T1), 12 horas após a cirurgia (T2), 24 horas após a cirurgia (T3), 48 horas após a cirurgia (T4), 72 horas após a cirurgia (T5) e 7 dias após a cirurgia (T6)]. As doses de morfina do momento T3 ao T5 e as reações adversas entre os dois grupos também foram registradas e comparadas. Resultados O nível de CD3+ e a razão CD4+/CD8+ de T2 a T5, e o nível de CD4+ e as células NK de T3 a T5 do Grupo COM foram significantemente maiores (p< 0,05) quando comparados ao Grupo MOR. A dose de morfina no pós-operatório e a incidência de prurido, náusea e vômito no pós-operatório foram significantemente menores no grupo MOR (p< 0,05). Conclusões Dexmedetomidina combinada com morfina para AICP no período pós-toracotomia pode melhorar a função dos linfócitos, reduzir o consumo de morfina e diminuir reações adversas durante a analgesia.

The geographical distribution patterns of Chrysoteuchia Hübner in China and description of a new species (Lepidoptera, Crambidae).

The geographical distribution patterns of Chrysoteuchia Hübner in China are analysed with MaxEnt and ArcGIS based on known localities and nineteen environmental variables. The results suggest that southeastern China is a highly suitable area, and Bio11 (mean temperature of the coldest quarter), Bio12 (annual precipitation) and Bio18 (precipitation of the warmest quarter) are revealed to be the main variables affecting the present distribution patterns. Among them, Bio18 is the strongest predictor with a 24.3% contribution. Furthermore, a new species from Tibet is added to the genus, Chrysoteuchialandryi sp. nov., and the male of C.curvicavus is described for the first time. Images of adults and their genitalia are illustrated, and two maps showing the geographical distribution patterns of Chrysoteuchia in China are provided.