Intestinal Microbiota Modulates the Antitumor Effect of Oncolytic Virus Vaccines in Colorectal Cancer.

BACKGROUND: Immunotherapies, such as oncolytic viruses, have become powerful cancer treatments, but only some patients with cancer can benefit from them, especially those with advanced-stage cancer, and new therapeutic strategies are needed to facilitate extended survival. The intestinal microbiota may contribute to colorectal cancer (CRC) carcinogenesis and the response to immunotherapy. However, whether and how the intestinal microbiota modulates the effects of oncolytic virus vaccines (OVVs) in CRC remain to be investigated. METHODS: We generated an MC38-gp33 CRC mouse model and treated it with OVV-gp33 in early and advanced stages. Probiotics, fecal microbiota transplantation (FMT), and antibiotics (ABX) were administered to regulate the microbial composition of CRC mice at an advanced stage. The tumor growth rate and survival time of the mice were recorded; 16S rDNA sequencing was used to analyze the microbial composition and flow cytometry was used to detect T-cell subset activity. RESULTS: OVV-gp33 treatment inhibited tumor growth and prolonged survival in the early stage of CRC but did not have a significant effect on the advanced stage of CRC. Moreover, 16S rDNA sequence analysis and flow cytometry showed significant differences in intestinal microbiota composition, microbial metabolites, and T-cell subsets in early and advanced-stage CRC. Probiotic and FMT treatment significantly enhanced the antitumor effect of OVV in the advanced stage of CRC with an increased abundance of activated CD8+ T cells and a decreased ratio of Treg cells, while depletion of the microbiota by ABX eliminated the antitumor activity of OVV with decreased CD8+ T-cell activation and upregulated Treg cells. CONCLUSIONS: These results indicate that the intestinal microbiota and microbial metabolites play an important role in the antitumor effect of OVV in CRC. Furthermore, altering the intestinal microbiota composition can modulate the antitumor and immunomodulatory effects of OVV in CRC.

Ion imprinted differential modulation system based on enhanced optic-fiber evanescent wave for sensitive and label-free detection of trace nickel ions.

An optical system with low cost monitoring, high sensitivity, strong selectivity and much lower nickel ion (Ni2+) content in tap water than the World Health Organization (WHO) standard (1.19 µM) has been prepared by a simple strategy. This proposed ion-imprinted differential modulation system is based on the Bragg grating (FBG) and microfiber interferometer structure, and the interferometer sensing surface is coated with a polydopamine (PDA)/graphene oxide (GO) film to enhance its sensitivity. Combined with the ion imprinting technique, the microfiber interferometer sensor sensitivity can reach 0.32 nm/nM with the detection limit of 0.66 nM in the low concentration range (Ni2+ concentration range is 0 nM-100 nM). The experiment not only studies the principle of microfiber interferometer and FBG and their refractive index and temperature performance, but also shows that the FBG power change has a good fitting relationship with wavelength change. In addition, this system performance by the amount of power difference rather than the amount of wavelength shift, which significantly saves on the high cost weight, and size associated with the use of spectral analyzers in traditional inspection systems. This study provides a novel and easy method to develop new sensors with higher comprehensive performance.

Infrared Spectroscopy of [M(CO2)n]+ (M = Ca, Sr, and Ba; n = 1-4) in the Gas Phase: Solvation-Induced Electron Transfer and Activation of CO2.

Cationic complexes of heavy alkaline earth metal and carbon dioxide [M(CO2)n]+ (M = Ca, Sr, and Ba) are produced by a laser vaporization-supersonic expansion ion source in the gas phase and are studied by infrared photodissociation spectroscopy in conjunction with quantum chemistry calculations. For the n = 1 complexes, the metal-ligand binding arises primarily from the electrostatic interaction with the CO2 ligand bound to the metal (+I) center in an end-on η1-O fashion. The more highly coordinated complexes [M(CO2)n]+ with n ≥ 2 are characterized to involve a [M2+(CO2-)] core ion with the CO2- ligand bound to the metal (+II) center in a bidentate η2-O, O manner. The activation of CO2 in forming a bent CO2- moiety occurs via solvation-induced metal cation-ligand electron transfer reactions. Bonding analyses reveal that the attractive forces between M2+ and CO2- in the core cation come mainly from electrostatic attraction, but the contribution of covalent orbital interactions should not be underestimated. The atomic orbitals of metal dications that are engaged in the orbital interactions are ns and (n - 1)d orbitals.

Novel dual: rod plate system for EOS improves vertebral wedging and permits spinal growth.

BACKGROUND: To determine whether single-stage, growth-friendly instrumentation with a plate-rod spinal system (PRSS) can substantially correct the deformity of EOS at surgery and continue to rectify the deformity throughout the growth period. METHODS: An observational study of 35 children with EOS treated by PRSS between February 2000 and October 2010 during a mean follow-up of 72 months. The mean age at surgery was 7 years. X-rays were taken preoperatively and postoperatively and at each follow-up. The Cobb angle, the apical vertebral wedge angle (AVWA), remaining rod lengths, maximal thoracic kyphosis and total T1-S1 heights were measured and compared. RESULTS: Thirty-one patients, 9 boys and 22 girls, with a mean age of 7 years were completed follow-up. The Cobb angle changed from 64° to 36° after initial surgery and 26° at the last follow-up. The mean AVWA was 15° postoperatively and 5° at the last follow-up. The mean rod tail reserve length decreased from 53 mm immediately after surgery to 12 mm at the last follow-up. The mean preoperative maximum thoracic kyphosis was 41° and changed to 35° and 30° postoperatively and at latest follow-up, respectively. The mean preoperative T1-S1 height for all 32 patients was 52 mm acute lengthening and 122 mm of lengthening by the end of follow-up, respectively. CONCLUSION: The PRSS provided immediate correction of most of the deformity at surgery and continued to rectify remaining scoliosis during the growth period. AVWA may be a useful method for monitoring the function of the PRSS in EOS.

Infrared photodissociation spectroscopy of mass-selected [TaO3(CO2)n]+ (n = 2-5) complexes in the gas phase.

We report a joint experimental and theoretical study on the structures of gas-phase [TaO3(CO2)n]+ (n = 2-5) ion-molecule complexes. Infrared photodissociation spectra of mass-selected [TaO3(CO2)n]+ complexes were recorded in the frequency region from 2200 to 2450 cm-1 and assigned through comparing with the simulated infrared spectra of energetically low-lying structures derived from quantum chemical calculations. With the increasing number of attached CO2 molecules, the larger clusters show significantly enhanced fragmentation efficiency and a strong band appears at around 2350 cm-1 near the free CO2 antisymmetric stretching vibration band, indicating only a small perturbation of CO2 molecules on the secondary solvation sphere while higher frequency bands corresponding to the core structure remain largely unaffected. A core structure [TaO3(CO2)3]+ is identified to which subsequent CO2 ligands are weakly attached and the most favorable cluster growth path is verified to proceed on the triplet potential energy surface higher in energy than that of ground states. Theoretical exploration reveals a two-state reactivity (TSR) scenario in which the energetically favored triplet transition state crosses over the singlet ground state to form a TaO3+ core ion, providing new information on the cluster formation correlated with the reactivity of tantalum metal oxides towards CO2.

Benzodiazepine-Receptor Agonist Utilization in Outpatients with Anxiety Disorder: A Retrospective Study Based on Electronic Healthcare Data from a Large General Tertiary Hospital.

Benzodiazepine-receptor agonists (BZRAs), including benzodiazepines (BZDs) and drugs related to BZDs (Z-drugs), are commonly used for anxiety, but often have side effects. We retrospectively investigated the utilization and prescription characteristics of BZRAs for patients with anxiety disorders in a large tertiary care general hospital between 2018 and 2021, based on electronic healthcare records. We also examined the pattern of simultaneous consumption of multiple BZRA drugs, and the diseases coexisting with anxiety that are associated with this. The numbers of patients and BZRA prescriptions increased over the 4 years. Moreover, 7195 prescriptions from 694 patients contained two or more BZRAs, of which 78.08% contained both BZDs and Z-drugs, 19.78% contained multiple BZDs, and 2.14% contained multiple Z-drugs. For anxiety patients with concomitant Alzheimer's disease or Parkinson's disease, and dyslipidemia, they were more likely to consume multiple BZRAs simultaneously, whereas patients with concomitant insomnia, depression, hypertension, diabetes, or tumors were less likely to consume multiple BZRAs (all p < 0.05). Furthermore, older patients who consume multiple BZRAs simultaneously may have higher probabilities of long-term drug use. Better interventions supporting standardized BZD utilization may be needed to minimize the side effects of inappropriate BZRA administration.

Direct observation on argon tagging nitrobenzene radical anion in gas phase: Infrared photodissociation spectroscopy and theoretical calculation.

The infrared photodissociation spectroscopy was applied to characterize nitrobenzene radical anion (NB-). NB- tagged by argon [NB(Ar)-] was prepared by a mixture of nitrobenzene/Ar through a supersonic ion source and then selected by a time-of-flight mass spectrometer. Eight strong peaks observed at 977.9, 999.6, 1059.8, 1275.7, 1309.7, 1339.7, 1367.6 and 1581.7 cm-1 in the fingerprint region were assigned to NB(Ar)-, corresponding to CC bending, CC stretching, CC bending + symmetric O-N stretching vibration, antisymmetric O-N and CC stretching vibration, antisymmetric O-N stretching and CH rocking vibration, CC stretching + antisymmetric O-N stretching vibration, C-N stretching vibration, and symmetric CC stretching vibration. Most interestingly, the distinguishable CH stretching vibrations were observed at 3006.5, 3048.6 and 3084.5 cm-1 absorptions. Combined with density functional theoretical (DFT) calculation, five tagging argon NB- isomers were optimized and analyzed with no imaginary frequency. The results indicated that most bond lengths in NB- become longer than those of neutral NB, except for the C1-C2/C4-C5 bonds, which are only slightly shorter than those of neutral NB, and the C-N bond, which is 0.085 A shorter in the anion. The NB- tagged by argon located on the nitro group had no change on bond parameters with Ar-tagging or not theoretically. Natural population analysis (NPA) show that the negative natural charges are mainly distributed on both oxygen atoms. And the one electron resonates between the nitro group and benzene ring. N-O bonds in NB- become much more polar than those of the neutral NB. This paper proved the usefulness to characterize NB(Ar)- and further explore the structures of NBn- (n > 1) clusters by infrared photodissociation spectroscopy combining with the time-of-flight mass spectrometer.

Analysis of injury and pain scores during fusion surgery for multisegmental lumbar spinal stenosis in elderly patients.

INTRODUCTION: Lumbar stenosis has become a common disease. Controversies exist regarding fusion surgery. MATERIAL AND METHODS: The patients were divided into groups per the method of fusion received: the posterolateral fusion group (group P) and the intervertebral fusion group (group I). The patients were further divided into groups based on the number of fusion segments: the 2-segment group (P2 and I2), the 3-segment group (P3 and I3), and the 4-segment group (P4 and I4). The operative time, intraoperative blood loss, blood transfusion volume, and postoperative drainage volume were summarized. In particular, wound healing appearance and management were observed. RESULTS: The operation time and blood transfusion volume of the P2 and P3 groups were significantly less than those of the I2 and I3 groups (p < 0.05). The postoperative drainage volume of group I4 was less than that of group P4 (p < 0.05). Postoperative numeric rating scale (NRS) scores of P2 and P3 groups were lower than those of I2 and I3 groups (p < 0.05), while the NRS scores of P4 group were higher than those of I4 group (p < 0.05). CONCLUSIONS: Posterolateral and intervertebral fusion techniques can be used in the surgical treatment of elderly patients with lumbar spinal stenosis. The posterolateral fusion method should be used when three or fewer segments require surgery. The intervertebral fusion method should be used when four segments require surgery.

Triple bonding between beryllium and nitrogen in HNBeCO.

The HNBeCO complex is generated via the reaction of a beryllium atom with a HNCO molecule in a solid neon matrix, which is identified via infrared absorption spectroscopy with isotopic substitutions. The complex is characterized to have a linear structure with a very short Be-N bond distance. Bonding analyses indicate that the complex involves an unprecedented HNBeCO triple bond consisting of two degenerate electron-sharing π bonds and a dative σ bond with the π bonds being much stronger than the σ bond.

Infrared spectroscopy of Be(CO2)4+ in the gas phase: electron transfer and C-C coupling of CO2.

Beryllium-carbon dioxide cation complexes Be(CO2)n+ are produced by a laser vaporization-supersonic expansion ion source in the gas phase. Mass-selected infrared photodissociation spectroscopy supplemented by theoretical calculations confirms that Be(CO2)4+ is a coordination saturated complex that can be assigned to a mixture of two isomers. The first structure involves a bent CO2- ligand that is bound in a monodentate η1-O coordination mode. Another isomer has a metal oxalate-type C2O4- moiety with a C-C hemibond.

Spinal Biomechanical Modelling in the Process of Lumbar Intervertebral Disc Herniation in Middle-Aged and Elderly.

Lumbar disc herniation is one of the common clinical diseases of the lower lumbar spine in orthopedics. The purpose is to remove the herniated disc nucleus pulposus tissue, remove the compressed part of the disease, and relieve symptoms, such as nerve pain. In the past, biomechanics research mostly relied on in vitro measurements, but the complicated internal environment of the human body prevented us from further measurement and research. However, with the development of computer technology, the use of computer CT scanning, software three-dimensional reconstruction, and displacement study three-dimensional spine biomechanics method makes the research of biomechanics into in vitro simulation stage and has gradually become the focus of current research. The postoperative biomechanics was simulated and the comparison model was established at the same time. At the same time, we combined the clinical follow-up data and studied the clinical data for the treatment of postoperative recurrence of lumbar disc herniation. We compared and analyzed the initial operation method and the experimental results and obtained the prevention of recurrence. The results showed that when one inferior articular process was removed, the lumbar spine appeared unstable to rotate to the opposite side; when one inferior articular process was completely removed, the movement of the lumbar spine in all directions was unstable. Better research on the biomechanical properties of the spine will help the diagnosis and treatment of clinical lumbar disc herniation. Therefore, when performing posterior lumbar spine surgery, not only should the exposure of the surgical field and thorough decompression be considered, but also the biomechanical properties of the lumbar spine should be comprehensively evaluated.

Highly Coordinated Heteronuclear Calcium-Iron Carbonyl Cation Complexes [CaFe(CO)n ]+ (n=5-12) with d-d Bonding.

Heteronuclear calcium-iron carbonyl cation complexes in the form of [CaFe(CO)n ]+ (n=5-12) are produced in the gas phase. Infrared photodissociation spectroscopy in conjunction with quantum chemical calculations confirm that the n=10 complex is the coordination saturated ion where a Fe(CO)4 fragment is bonded with a Ca(CO)6 fragment through two side-on bridging carbonyl ligands. Bonding analysis indicates that it is best described by the bonding interactions between a [Ca(CO)6 ]2+ dication and an [Fe(CO)4 ]- anion forming a Fe→Ca d-d dative bond in the [(CO)6 Ca-Fe(CO)4 ]+ structure, which enriches the pool of experimentally observed complexes of calcium that mimic transition metal compounds. The molecule is the first example of a heteronuclear carbonyl complex featuring a d-d bond between calcium and a transition metal.

Formation and Characterization of BeFe(CO)4 - Anion with Beryllium-Iron Bonding.

Heteronuclear BeFe(CO)4 - anion complex is generated in the gas phase, which is detected by mass-selected infrared photodissociation spectroscopy in the carbonyl stretching frequency region. The complex is characterized to have a Be-Fe bonded Be-Fe(CO)4 - structure with C3v symmetry and all of the four carbonyl ligands bonded on the iron center. Quantum chemical studies indicate that the complex has a quite short Be-Fe bond. Besides one electron-sharing σ bond, there are two additional, albeit weak, Be ← Fe(CO)4 - dative π bonding interactions. The findings imply that metal-metal bonding between s-block and transition metals is viable under suitable coordination environment.

A Homoleptic Beryllium Carbonyl Complex with an End-On and Side-On Bridging Carbonyl Ligand.

Homoleptic dinuclear beryllium carbonyl cation complexes have been produced and characterized in the gas phase. Infrared photodissociation spectroscopic and theoretical results confirm that Be2 (CO)5 + is a coordination saturated complex that can be assigned to a mixture of two almost isoenergetic structural isomers. Besides a beryllium-beryllium single-bonded (OC)2 Be-Be(CO)3 + isomer, another structure involving an unusual end-on and side-on bridging carbonyl ligand with very low carbonyl stretching frequency is identified.

Beryllium Atom Mediated Dinitrogen Activation via Coupling with Carbon Monoxide.

The reactions of laser-ablated beryllium atoms with dinitrogen and carbon monoxide mixtures form the end-on bonded NNBeCO and side-on bonded (η2 -N2 )BeCO isomers in solid argon, which are predicted by quantum chemical calculations to be almost isoenergetic. The end-on bonded complex has a triplet ground state while the side-on bonded isomer has a singlet electronic ground state. The complexes rearrange to the energetically lowest lying NBeNCO isomer upon visible light excitation, which is characterized to be an isocyanate complex of a nitrene derivative with a triplet electronic ground state. A bonding analysis using a charge- and energy decomposition procedure reveals that the electronic reference state of Be in the NNBeCO isomers has an 2s0 2p2 excited configuration and that the metal-ligand bonds can be described in terms of N2 →Be←CO σ donation and concomitant N2 ←Be→CO π backdonation. The results demonstrate that the activation of N2 with the N-N bond being completely cleaved can be achieved via coupling with carbon monoxide mediated by a main group atom.

Infrared Photodissociation Spectroscopy of Mass-Selected Cu2O2(CO)n+ Clusters in the Gas Phase.

Stoichiometric Cu2O2(CO)n+ (n = 3-7) clusters were generated via a laser vaporization supersonic cluster source in the gas phase and identified by infrared photodissociation spectroscopy in the C-O stretching region. The infrared spectra were interpreted, and the cluster structures were determined by density functional calculations. The ground states of the Cu2O2(CO)n+ complexes were formed by a dicopper superoxide carbonyl with [(OC)xCuOOCu(CO)y]+ (x + y = n) structures in which the CO ligands coordinate a zigzag Cu(OO)Cu+ core. The structural characterization for the Cu(OO)Cu+ core-based clusters is crucial in order to correctly understand the associated reactions catalyzed by metal clusters.

Side-On Bonded Beryllium Dinitrogen Complexes.

The preparation and spectroscopic identification of the complexes NNBe(η2 -N2 ) and (NN)2 Be(η2 -N2 ) and the energetically higher lying isomers Be(NN)2 and Be(NN)3 are reported. NNBe(η2 -N2 ) and (NN)2 Be(η2 -N2 ) are the first examples of covalently side-on bonded N2 adducts of a main-group element. The analysis of the electronic structure using modern methods of quantum chemistry suggests that NNBe(η2 -N2 ) and (NN)2 Be(η2 -N2 ) should be classified as π complexes rather than metalladiazirines.

Reactions of Transition-Metal Carbyne Cations with Ethylene in the Gas Phase.

The reactions of iridium- and osmium-carbyne hydride cations [HIrCH]+ and [HOsCH]+ with ethylene have been studied using mass spectrometry with isotopic-labeling in the gas phase. The carbyne reactivity is compared with that of the rhodium, cobalt, and iron analogues [TMCH2]+ (TM = Fe, Co, and Rh), which were determined to have the carbene structures. Besides the cycloaddition/dehydrogenation reaction in forming the [TMC3H4]+ + H2 (TM = Ir and Os) products, a second reaction pathway producing the [TMC2H2]+ ion and CH4 via triple hydrogen atom transfer reactions to the carbyne carbon is observed to be the major channel. The latter channel is not observed in the rhodium, cobalt, and iron carbene cation reactions. Quantum-chemical calculations indicate that the distinct reactivity is not due to different initial structures of the reactants. Both reaction channels are predicted to be thermodynamically exothermic and kinetically facile for the carbyne cations, and the reactions proceed with the initial formation of a carbene intermediate via hydride-carbyne coupling. The latter channel is also exothermic but kinetically unfavorable for the rhodium, cobalt, and iron carbene cations.

Label-Free Detection of Cancer Biomarkers Using an In-Line Taper Fiber-Optic Interferometer and a Fiber Bragg Grating.

A compact and label-free optical fiber sensor based on a taper interferometer cascaded with a fiber Bragg grating (FBG) is proposed and experimentally demonstrated for detection of a breast cancer biomarker (HER2). The tapered fiber-optic interferometer is extremely sensitive to the ambient refractive index (RI). In addition, being insensitive to the RI variation, the FBG can be applied as a temperature thermometer due to its independent response to the temperature. Surface functionalization to the sensor is carried out to achieve specific targeting of the unlabeled biomarkers. The result shows that the proposed sensor presents a low limit-of-detection (LOD) of 2 ng/mL, enabling its potentials of application in early diagnosis on the breast cancer.

Knockdown of COPS3 Inhibits Lung Cancer Tumor Growth in Nude Mice by Blocking Cell Cycle Progression.

COPS3 encodes the third subunit of the COP9 signalosome and its aberrant expression is associated with many RITE ("Region of Increased Tumor Expression") genes in lung cancer tissues. To elucidate the specific role of COPS3 in lung cancer, we examined its expression in lung cancer tissues by immunohistochemical staining. We found that COPS3 was overexpressed in most of the lung cancer samples examined, particularly in small cell carcinoma and squamous cell carcinoma. The expression of COPS3 protein was positively correlated with the level of Ki-67 cell proliferation index (p=0.001) and negatively related to the degree of tumor differentiation (p=0.012). In a xenograft tumor model in nude mice, shRNA-knockdown of COPS3 significantly reduced tumor growth. In lung adenocarcinoma A549 cells, shRNA-knockdown of COPS3 induced cell cycle arrest at G0/G1 phase by upregulating the cell cycle regulator protein P21 and downregulating cyclin B1 and CDK4. These data suggest that COPS3 may promote tumor growth by regulating cell-cycle associated proteins.