Progress of researches on Blastocystis hominis infection among patients with inflammatory bowel disease and irritable bowel syndrome / 中国血吸虫病防治杂志

Blastocystis is a common unicellular intestinal protozoa in humans and animals, and the most common clinical manifestations of infections include abdominal pain and diarrhea. Based on the sequence of the small-subunit ribosomal RNA (SSU rRNA) gene, 28 subtypes of B. hominis (ST1 to ST17, ST21 and ST23 to ST32) have been characterized. Previous studies have demonstrated that B. hominis infection is strongly associated with inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other intestinal diseases, which threatens the health and quality of life among patients with B. hominis infection and is considered as an important public health problem. This review summarizes the progress of researches on B. hominis infection among IBD and IBS patients during the past 20 years, so as to provide insights into management of blastocystosis in China.

A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike

A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here we describe a new deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers of spike mutations impact antibody neutralization and pseudovirus infection. We demonstrate this new platform by making libraries of the Omicron BA.1 and Delta spikes. These libraries each contain ~7000 distinct amino-acid mutations in the context of up to ~135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor binding domain, N-terminal domain, and S2 subunit of spike. Overall, this work establishes a high-throughput and safe approach to measure how ~105 combinations of mutations affect antibody neutralization and spike-mediated infection. Notably, the platform described here can be extended to the entry proteins of many other viruses.

Subcutaneous delivery of an antibody against SARS-CoV-2 from a supramolecular hydrogel depot

Prolonged maintenance of therapeutically-relevant levels of broadly neutralizing antibodies (bnAbs) is necessary to enable passive immunization against infectious disease. Unfortunately, protection only lasts for as long as these bnAbs remain present at a sufficiently high concentration in the body. Poor pharmacokinetics and burdensome administration are two challenges that need to be addressed in order to make pre- and post-exposure prophylaxis with bnAbs feasible and effective. In this work, we develop a supramolecular hydrogel as an injectable, subcutaneous depot to encapsulate and deliver antibody drug cargo. This polymer-nanoparticle (PNP) hydrogel exhibits shear-thinning and self-healing properties that are required for an injectable drug delivery vehicle. In vitro drug release assays and diffusion measurements indicate that the PNP hydrogels prevent burst release and slow the release of encapsulated antibodies. Delivery of bnAbs against SARS-CoV-2 from PNP hydrogels is compared to standard routes of administration in a preclinical mouse model. We develop a multi-compartment model to understand the ability of these subcutaneous depot materials to modulate the pharmacokinetics of released antibodies; the model is extrapolated to explore the requirements needed for novel materials to successfully deliver relevant antibody therapeutics with different pharmacokinetic characteristics.

COVID-19 vaccination recruits and matures cross-reactive antibodies to conserved epitopes in endemic coronavirus Spike proteins

The COVID-19 pandemic has triggered the first widespread vaccination campaign against a coronavirus. Most vaccinated subjects are naive to SARS-CoV-2, however almost all have previously encountered other coronaviruses (CoVs) and the role of this immunity in shaping the vaccine response remains uncharacterized. Here we use longitudinal samples and highly-multiplexed serology to identify mRNA-1273 vaccine-induced antibody responses against a range of CoV Spike epitopes and in both phylogenetically conserved and non-conserved regions. Whereas reactivity to SARS-CoV-2 epitopes showed a delayed but progressive increase following vaccination, we observed distinct kinetics for the endemic CoV homologs at two conserved sites in Spike S2: these became detectable sooner, and decayed at later timepoints. Using homolog-specific depletion and alanine-substitution experiments, we show that these distinctly-evolving specificities result from cross-reactive antibodies as they mature against rare, polymorphic residues within these epitopes. Our results reveal mechanisms for the formation of antibodies with broad reactivity against CoVs.

Flexible robust binder-free carbon nanotube membranes for solid state and microcapacitor application.

We present a liquid phase post synthesis self-assemble protocol that transforms trillions of carbon nanotubes (CNTs) in powder form into densely packed flexible, robust and binder-free macroscopic membranes with a hierarchical pore structure. We employ charge transfer engineering to spontaneously disperse the CNTs in a liquid medium. The processing protocol has limited or no impact on the intrinsic properties of the CNTs. As the thickness of the CNT membrane is increased, we observed a gradual transition from high flexibility to buckling and brittleness in the flexural properties of the membranes. The binder-free CNT membranes have bulk mass density greater than that of water (1.0 g cm-3). We correlate the mass of the CNTs in the membrane to the thickness of the membrane and obtained a bulk mass density of ∼1.11 g cm-3 ± 0.03 g cm-3. We demonstrate the use of the CNT membranes as electrode in a pristine and oxidized single/stacked solid-state capacitor as well as pristine interdigitated microcapacitor that show time constant of ∼32 ms with no degradation in performance even after 10 000 cycles. The capacitors show very good temperature dependence over a wide range of temperatures with good cycling performance up to 90 °C. The specific capacitance of the pseudocapacitive CNT electrode at room temperature was 72 F g-1 and increased to 100 F g-1 at 70 °C. The leakage current of bipolar stacked solid state capacitor was ∼100 nA cm-2 at 2.5 V when held for 72 h.

Epidemiological characteristics and related risk factors on placental abruption in Hebei province / 中华流行病学杂志

Objective: The aim of this study was to assess the risk factors and epidemiological characteristics of placental abruption (PA) in Hebei province. Methods: A cross-sectional survey was conducted to collect data on 218 880 pregnant women who were hospitalized in 22 hospitals which were under a monitoring program, in Hebei province, from January 1, 2013 to December 31, 2016. Data regarding epidemiological characteristics as time distribution, population distribution and related risk factors of placental abruption were gathered and analyzed. Results: In this cohort study, 218 880 women were included, with 669 (0.31%) of the pregnant women having PA. The overall prevalence rates were higher in the South than in the north parts of the area and higher in more developed regional economic centers. The average age of women having the episode was (27.87±4.50) years and presented "J" distribution on the prevalence of maternal age. Results from the multivariate regression analysis showed that the following factors were independently at risk for placental abruption: pregnancy the including hypertension (OR=1.65, 95%CI: 1.09-2.50), mild preeclampsia (OR=3.65, 95%CI: 2.40-5.56), severe preeclampsia (OR=4.72, 95%CI: 3.86-5.76) and anemia (OR=2.41, 95%CI: 2.05-2.83) which were all increased in pregnant women with PA compared with the normal female population without placental abruption. Conclusions: Placental abruption seemed to be associated with a moderate increasing risk of age, and was seen higher in those population older than 35 or younger than 20 year-olds. It was suggested that appropriate inoculation programs should be taken in different regions, especially on high-risk groups. Health education on related disease was of great significance for improving the prenatal outcome.

Factors associated with illicit drug use intention in secondary vocational school students based on theory of triadic influence / 中华流行病学杂志

Objective: To explore the factors associated with illicit drug use (IDU) intention in secondary vocational school students based on theory of triadic influence (TTI), and provide theoretical foundation for IDU prevention education. Methods: A total of 8 870 students were selected from secondary vocational schools in 5 cities in China through multistage cluster sampling. A self-administered questionnaire was used to collect the information about students' sensation seeking (SS), parental monitoring (PM), perceived availability of drug (PAD), social benefit expectancies(SBE), refusal efficacy (RE) and social norms and IDU intention. Based on the TTI, the logistic regression model was used to analyze the factors associated with IDU. Results: Among the intrapersonal stream of influence, the higher levels of SS was the risk factor associated with IDU (OR=1.71, 95%CI: 1.22-2.41, P<0.01), medium RE level (OR=0.18, 95%CI: 0.14-0.23, P<0.001) and high RE level (OR=0.17, 95%CI: 0.13-0.22, P<0.001) were the protective factors for IDU intention. Among the interpersonal stream of influence, medium PM level (OR=0.46, 95%CI: 0.37- 0.56, P<0.001) and high PM level (OR=0.33, 95%CI: 0.24-0.46, P<0.001) were the protective factors for IDU intention, perceived others' drug use as well as perceived others' approval of substance use were risk factors for IDU intentions (P<0.001); Among sociocultural environmental stream of influence, perceived easy availability of drugs (OR=3.47, 95%CI: 2.69-4.48, P<0.001) and perceived SBE of drugs (OR=2.04, 95%CI: 1.69-2.46, P<0.001) were risk factors for IDU intentions (P<0.001). Conclusions: High levels of SS and SBE, perceived easier availability of substance, perceived others' substance use and perceived others' approval of substance use positively predict the students' intention of IDU. IDU prevention education for adolescents should be focused on the above factors, and parental supervision and students' refuse skills should be improved.

Role of indoleamine 2,3-dioxygenase in an inflammatory model of murine gingiva.

BACKGROUND AND OBJECTIVE: Indoleamine 2,3-dioxygenase (IDO) is one of the major pathways for metabolism of tryptophan in a variety of cells, including immune cells. Increasing evidence indicates that IDO is a critical player in establishing the balance between immunity and tolerance and ultimately in the maintenance of homeostasis. By inducing inflammation in gingival tissue, we tested the hypothesis that IDO is a pivotal player in regulating the immune and inflammatory responses of gingiva. MATERIAL AND METHODS: We utilized the IDO knockout mouse model in conjunction with lipopolysaccharide (LPS)-induced inflammation. Accordingly, wild-type and IDO knockout mice were injected with LPS or vehicle in the anterior mandibular gingiva, twice over a 2-wk period, which was followed by procurement of gingival tissue for histopathology and preparation of tissue for flow cytometry-based studies. RESULTS: Clinical and histological examinations revealed a marked adverse impact of IDO deficiency on gingival inflammation. These observations were consistent with a more marked increase in the number of cells positive for the proinflammatory cytokine interleukin (IL)-17, but no significant change in the number of cells positive for the anti-inflammatory cytokine IL-10, in LPS-treated IDO knockout mice. Consistent with the more marked proinflammatory impact of IDO deficiency, the percentage of regulatory T cells was much reduced in gingival tissue of LPS-treated IDO knockout mice than in gingival tissue of wild-type mice. These proinflammatory changes were accompanied with a prominent increase in apoptotic and necrotic cell death in gingival tissue of IDO knockout mice compared with wild-type mice. CONCLUSION: Collectively, our findings support a major role for IDO in the development of gingival inflammation, as an example of an inflammatory condition, and lay the foundation for subsequent studies to explore it as a novel immunotherapy target.

Influence of evanescent wave on birefringent microplates.

Mechanical action caused by the optical forces connected with the canonical momentum density associated with the local wavevector or Belinfante's spin angular momentum is experimentally verified. The helicity-dependent and the helicity-independent forces determined by spin momenta of different nature open attractive prospects for the use of optical structures for manipulating minute quantities of matter of importance in nanophysics, nanooptics and nanotechnologies, precision chemistry and pharmacology and in numerous other areas. Investigations in this area reveal new, extraordinary manifestations of optical forces, including the helicity-independent force caused by the transverse helicity-independent spin or vertical spin of a diagonally polarized wave, which was not observed and exploited up to recently. The main finding of our study consists in a direct experimental demonstration of the physical existence and mechanical action of this recently discovered extraordinary transverse component of the spin here arising in an evanescent light wave due to the total internal reflection of a linearly polarized probing beam with azimuthal angle 45° at the interface between the birefringent plate and air, which is oriented perpendicularly to the wavevector of an evanescent wave and localized over the boundary of the transparent media with polarization-dependent refraction indices.

A cross-sectional study on the biopsychosocial factors influencing quality of life and adherence to treatment of people living with HIV (PLHIV) in the National Capital Region / The Health Sciences Journal

Introduction@#This study investigated the association of selected biopsychosocial factors (i.e., CD4 cell count, self-stigma, and social stigma) with the quality of life and adherence to treatment of people living with HIV in the National Capital Region.@*Methods@#A cross-sectional study design was conducted to document the health status and behavior of respondents affiliated with a clinic in Quezon City. Participants answered an online questionnaire containing the Berger HIV Stigma Scale, WHO-QOL for HIV, and HIV Treatment Adherence SelfEfficacy Scale. Bivariate analyses and prevalence risk ratios were used to determine the association of selected biopsychosocial factors with quality of life and adherence to treatment.@*Results@#One hundred respondents were analyzed, of which 42% had CD4 cell counts < 350 cells/mm3, 43% had high self-stigma and 36% had high social stigma while 11% had poor QOL and 7% had poor ATT. There was no significant association of CD4 cell count, self-stigma and social stigma with quality of life and with adherence to treatment.@*Conclusion@#A weak association was noted between poor QOL and low CD4 cell counts and among those who felt higher social stigma, but the relationships were not significant. The association between poor ATT and the selected biopsychosocial factors was not significant.

Additional approaches to solving the phase problem in optics.

The paper presents principal approaches to diagnosing the structure-forming skeleton of a complex optical field. Analysis of optical field singularity algorithms, depending on intensity discretization and image resolution, has been carried out. An optimal approach is chosen, which allows us to get much closer to the solution of the phase problem of localization speckle-field special points. The use of a "window" 2D Hilbert transform for reconstruction of the phase distribution of the intensity of a speckle field is proposed. It is shown that the advantage of this approach consists in the invariance of a phase map to a position change of the kernel of transformation and in a possibility to reconstruct the structure-forming elements of the skeleton of an optical field, including singular points and saddle points. We demonstrate the possibility to reconstruct the equi-phase lines within a narrow confidence interval and introduce an additional algorithm for solving the phase problem for random 2D intensity distributions.

[Biosynthesis of secondary metabolites in methanotrophs: biochemical and genetic aspects (review)].

The review summarizes the data on the metabolic potential of methanotrophs as producers of biopolymers, alternative biofuel, bioprotectants, and other secondary metabolites. The work provides the examples of modern 'omic' technologies used for genetic engineering of efficient methanotrophic producers.

[THE CLINICAL COURSE OF THE ISOLATED EFFECTS OF EXTENSIVE SMALL INTESTINE RESECTION IN THE LATE POSTOPERATIVE PERIOD].

UNLABELLED: The purpose is the postoperative period study of clinical and functional status of patients after small intestine resection, which was performed in different volume MATERIAL AND METHODS: 91 patients with sequelae of small intestine resection in different terms after the operation were surveyed. Patients were assessed for clinical symptoms on a scale "Method of evaluating intestinal failure after gastric resection", in our own modifications, clinical-laboratory and biochemical blood examination, ultrasound examination of abdominal cavity and kidneys, x-ray examination of the gastrointestinal tract, esophagogastroduodenoscopy with histological examination of the mucosa. We determined the scatology, the consistency of the feces on the Bristol scale, concentration and profile of short chain fatty acids in coprofiltrates. Blood serum Citrulline was determined using high performance liquid chromatography on the chromatograph "Stayer". The degree of nutritional risk was assessed using screen questionnaire NRS-2002 RESULTS: Analysis of clinical, anthropometric and laboratory data showed that patients with residual stumps of the small intestine more than 2 meters have a distinct tendency to stabilize their condition, confirmed by the level of citrulline in the serum. At the same time complete adaptation does not occur, because the main reason of the operation is adhesive intestinal obstruction with chronic relapsing course. Patients with stumps of the small intestine less than 2 m have highly individual adaptation, which may be due to a small sample of patients in this group. The detected changes in the concentration and profile of coprofiltrat short-chain fatty acids allow differentiated approach to therapy of diarrhea syndrome as the main clinical manifestations of the effects of isolated small intestine resection.

DNA-binding studies of AV-153, an antimutagenic and DNA repair-stimulating derivative of 1,4-dihydropiridine.

UNLABELLED: The ability to intercalate between DNA strands determines the cytotoxic activity of numerous anticancer drugs. Strikingly, intercalating activity was also reported for some compounds considered to be antimutagenic. The aim of this study was to determine the mode of interaction of DNA with the antimutagenic and DNA repair-stimulating dihydropyridine (DHP) AV-153. DNA and AV-153 interactions were studied by means of UV/VIS spectroscopy, fluorimetry and infrared spectroscopy. Compound AV-153 is a 1,4 dihydropyridine with ethoxycarbonyl groups in positions 3 and 5. Computer modeling of AV-153 and DNA interactions suggested an ability of the compound to dock between DNA strands at a single strand break site in the vicinity of two pyrimidines, which was confirmed in the present study. AV-153 evidently interacted with DNA, as addition of DNA to AV-153 solutions resulted in pronounced hyperchromic and bathochromic effects on the spectra. Base modification in a plasmid by peroxynitrite only minimally changed binding affinity of the compound; however, induction of single-strand breaks using Fenton's reaction greatly increased binding affinity. The affinity did not change when the ionic strength of the solution was changed from 5 to 150 mM NaCl, although it increased somewhat at 300 mM. Neither was it influenced by temperature changes from 25 to 40°C, however, it decreased when the pH of the solution was changed from 7.4 to 4.7. AV-153 competed with EBr for intercalation sites in DNA: 116 mM of the compound caused a two-fold decrease in fluorescence intensity. FT-IR spectral data analyses indicated formation of complexes between DNA and AV-153. The second derivative spectra analyses indicated interaction of AV-153 with guanine, cytosine and thymine bases, but no interaction with adenine was detected. CONCLUSIONS: The antimutagenic substance AV-153 appears to intercalate between the DNA strands at the site of a DNA nick in the vicinity of two pyrimidines.

Self-action of continuous laser radiation and Pearcey diffraction in a water suspension with light-absorbing particles.

Water suspension of light-absorbing nano-sized particles is an example of a medium in which non-linear effects are present at moderate light intensities favorable for optical treatment of organic and biological objects. We study experimentally the phenomena emerging in a thin layer of such a medium under the action of inhomogeneous light field formed due to the Pearcey diffraction pattern near a microlens focus. In this high-gradient field, the light energy absorbed by the particles induces inhomogeneous distribution of the medium refraction index, which results in observable self-diffraction of the incident light, here being strongly sensitive to the medium position with respect to the focus. This technique, based on the complex spatial structure of both the incident and the diffracted fields, can be employed for the detection and measurement of weak non-linearities.

Self-diffraction of continuous laser radiation in a disperse medium with absorbing particles.

We study the self-action of light in a water suspension of absorbing subwavelength particles. Due to efficient accumulation of the light energy, this medium shows distinct non-linear properties even at moderate radiation power. In particular, by means of interference of two obliquely incident beams, it is possible to create controllable phase and amplitude gratings whose contrast, spatial and temporal parameters depend on the beams' coherence and power as well as the interference geometry. The grating characteristics are investigated via the beams' self-diffraction. The main mechanism of the grating formation is shown to be thermal, which leads to the phase grating; a weak amplitude grating also emerges due to the particles' displacements caused by the light-induced gradient and photophoretic forces. These forces, together with the Brownian motion of the particles, are responsible for the grating dynamics and degradation. The results and approaches can be used for investigation of the thermal relaxation and kinetic processes in liquid suspensions.

Circular motion of particles suspended in a Gaussian beam with circular polarization validates the spin part of the internal energy flow.

Non-spherical dielectric microparticles were suspended in a water-filled cell and exposed to a coherent Gaussian light beam with controlled state of polarization. When the beam polarization is linear, the particles were trapped at certain off-axial position within the beam cross section. After switching to the right (left) circular polarization, the particles performed spinning motion in agreement with the angular momentum imparted by the field, but they were involved in an orbital rotation around the beam axis as well, which in previous works [Y. Zhao et al, Phys. Rev. Lett. 99, 073901 (2007)] was treated as evidence for the spin-to orbital angular momentum conversion. Since in our realization the moderate focusing of the beam excluded the possibility for such a conversion, we consider the observed particle behavior as a demonstration of the macroscopic "spin energy flow" predicted by the theory of inhomogeneously polarized paraxial beams [A. Bekshaev et al, J. Opt. 13, 053001 (2011)].

Comparative effects of angiotensin receptor blockade and ACE inhibition on the fibrinolytic and inflammatory responses to cardiopulmonary bypass.

The effects of angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor blockade (ARB) on fibrinolysis and inflammation after cardiopulmonary bypass (CPB) are uncertain. This study tested the hypothesis that ACE inhibition enhances fibrinolysis and inflammation to a greater extent than ARB in patients undergoing CPB. One week to 5 days before surgery, patients were randomized to ramipril 5 mg/day, candesartan 16 mg/day, or placebo. ACE inhibition increased intraoperative bradykinin and tissue-type plasminogen activator (t-PA ) concentrations as compared to AR B. Both ACE inhibition and AR B decreased the need for plasma transfusion relative to placebo, but only ACE inhibition decreased the duration of hospital stay. Neither ACE inhibition nor AR B significantly affected concentrations of plasminogen activator inhibitor-1 (PAI -1), interleukin (IL )-6, IL -8, or IL -10. ACE inhibition enhanced intraoperative fibrinolysis without increasing the likelihood of red-cell transfusion. By contrast, neither ACE inhibition nor ARB affected the inflammatory response. ACE inhibitors and ARBs may be safely continued until the day of surgery.

Orbital rotation without orbital angular momentum: mechanical action of the spin part of the internal energy flow in light beams.

The internal energy flow in a light beam can be divided into the "orbital" and "spin" parts, associated with the spatial and polarization degrees of freedom of light. In contrast to the orbital one, experimental observation of the spin flow seems problematic because it is converted into an orbital flow upon tight focusing of the beam, usually applied for energy flow detection by means of the mechanical action upon probe particles. We propose a two-beam interference technique that results in an appreciable level of spin flow in moderately focused beams and detection of the orbital motion of probe particles within a field where the transverse energy circulation is associated exclusively with the spin flow. This result can be treated as the first demonstration of mechanical action of the spin flow of a light field.

A facile, branched DNA assay to quantitatively measure glucocorticoid receptor auto-regulation in T-cell acute lymphoblastic leukemia / 癌症

Glucocorticoid (GC) steroid hormones are used to treat acute lymphoblastic leukemia (ALL) because of their pro-apoptotic effects in hematopoietic cells. However, not all leukemia cells are sensitive to GC, and no assay to stratify patients is available. In the GC-sensitive T-cell ALL cell line CEM-C7, auto-up-regulation of RNA transcripts for the glucocorticoid receptor (GR) correlates with increased apoptotic response. This study aimed to determine if a facile assay of GR transcript levels might be promising for stratifying ALL patients into hormone-sensitive and hormone-resistant populations. The GR transcript profiles of various lymphoid cell lines and 4 bone marrow samples from patients with T-cell ALL were analyzed using both an optimized branched DNA (bDNA) assay and a real-time quantitative reverse transcription-polymerase chain reaction assay. There were significant correlations between both assay platforms when measuring total GR (exon 5/6) transcripts in various cell lines and patient samples, but not for a probe set that detects a specific, low abundance GR transcript (exon 1A3). Our results suggest that the bDNA platform is reproducible and precise when measuring total GR transcripts and, with further development, may ultimately offer a simple clinical assay to aid in the prediction of GC-sensitivity in ALL patients.