Methylobacterium infection-induced peritonitis in a patient with renal insufficiency: A case report and literature review.

Clinical pharmacists participated in the drug therapy of peritonitis caused by Methylobacterium infection in a patient with renal insufficiency. Based on the knowledge of clinical pharmacy, the patient's condition and laboratory parameters, the literature, and the pharmacokinetic/pharmacodynamic characteristics of antibiotics, amikacin in combination with ciprofloxacin was suggested for anti-infection therapy. During the treatment, clinical pharmacists timely evaluated the efficacy of antibiotics, monitored the adverse reactions, and provided individualized pharmaceutical care in the patient.

Selective COX-2 inhibitors do not increase gastrointestinal reactions after colorectal cancer surgery: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of selective COX-2 inhibitors in preventing colorectal cancer recurrence has been demonstrated, however it is unknown how safe and successful they will be over the long term. As a result, we looked at the efficacy, safety, and consequences of adding COX-2 inhibitors to the treatment plan afterward. METHODS: In patients with advanced colorectal cancer, we compared the efficacy of celecoxib at two different doses (200 mg twice day and 400 mg twice daily) with placebo. To evaluate the impacts of post-treatment, several datasets from inception to June 2022 were searched. Response rate, illness control rate, and 3-year survival were the main results. And evaluated several safety outcomes, particularly those that were susceptible to adverse events. RESULTS: The study comprised a total of 9 randomized controlled trials (3206 participants). Celecoxib and rofecoxib doidn't significantly improved the 1-3 year remission rate (OR, 1.57 [95% CI: 0.95-2.57]) and disease control rate (OR, 1.08 [95% CI: 0.99-1.17]). Subgroup analysis of different doses showed that 400 mg of celecoxib significantly improved the response rate (OR, 2.82 [95%CI: 1.20-6.61]). 200 mg celecoxib was not significant (OR, 1.28 [95% CI: 0.66-2.49]). Rofecoxib also did not fully improve disease response rates. Celecoxib at any dose improved 3-year survival (OR, 1.21 [95% CI: 1.02-1.45]). It is important to note that COX-2 inhibitors did not significantly enhance the likelihood of adverse events including gastrointestinal or cardiovascular side effects at any dose. CONCLUSIONS: For patients with advanced colorectal cancer, a reasonable chemoprevention regimen can include celecoxib 400 mg twice daily.

Reciprocal positive regulation between BRD4 and YAP in GNAQ-mutant uveal melanoma cells confers sensitivity to BET inhibitors.

Uveal melanoma (UM) is the most common intraocular cancer in adults. UMs are usually initiated by a mutation in GNAQ or GNA11 (encoding Gq or G11, respectively), unlike cutaneous melanomas (CMs), which usually carry a BRAF or NRAS mutation. Currently, there are no clinically effective targeted therapies for UM carrying Gq/11 mutations. Here, we identified a causal link between Gq activating mutations and hypersensitivity to bromodomain and extra-terminal (BET) inhibitors. BET inhibitors transcriptionally repress YAP via BRD4 regardless of Gq mutation status, independently of Hippo core components LATS1/2. In contrast, YAP/TAZ downregulation reduces BRD4 transcription exclusively in Gq-mutant cells and LATS1/2 double knockout cells, both of which are featured by constitutively active YAP/TAZ. The transcriptional interdependency between BRD4 and YAP identified in Gq-mutated cells is responsible for the preferential inhibitory effect of BET inhibitors on the growth and dissemination of Gq-mutated UM cells compared to BRAF-mutated CM cells in both culture cells and animal models. Our findings suggest BRD4 as a viable therapeutic target for Gq-driven UMs that are addicted to unrestrained YAP function.

PTEN loss confers sensitivity to rapalogs in clear cell renal cell carcinoma.

Rapalogs (everolimus and temsirolimus) are allosteric mTORC1 inhibitors and approved agents for advanced clear cell renal cell carcinoma (ccRCC), although only a subset of patients derive clinical benefit. Progress in genomic characterization has made it possible to generate comprehensive profiles of genetic alterations in ccRCC; however, the correlations between recurrent somatic mutations and rapalog efficacy remain unclear. Here, we demonstrate by using multiple patient-derived ccRCC cell lines that compared to PTEN-proficient cells, PTEN-deficient cells exhibit hypersensitivity to rapalogs. Rapalogs inhibit cell proliferation by inducing G0/G1 arrest without inducing apoptosis in PTEN-deficient ccRCC cell lines. Using isogenic cell lines generated by CRISPR/Cas9, we validate the correlation between PTEN loss and rapalog hypersensitivity. In contrast, deletion of VHL or chromatin-modifying genes (PBRM1, SETD2, BAP1, or KDM5C) fails to influence the cellular response to rapalogs. Our mechanistic study shows that ectopic expression of an activating mTOR mutant (C1483F) antagonizes PTEN-induced cell growth inhibition, while introduction of a resistant mTOR mutant (A2034V) enables PTEN-deficient ccRCC cells to escape the growth inhibitory effect of rapalogs, suggesting that PTEN loss generates vulnerability to mTOR inhibition. PTEN-deficient ccRCC cells are more sensitive to the inhibitory effects of temsirolimus on cell migration and tumor growth in zebrafish and xenograft mice, respectively. Of note, PTEN protein loss as detected by immunohistochemistry is much more frequent than mutations in the PTEN gene in ccRCC patients. Our study suggests that PTEN loss correlates with rapalog sensitivity and could be used as a marker for ccRCC patient selection for rapalog therapy.

BAP1 loss augments sensitivity to BET inhibitors in cancer cells.

The tumor suppressor gene BAP1 encodes a widely expressed deubiquitinase for histone H2A. Both hereditary and acquired mutations are associated with multiple cancer types, including cutaneous melanoma (CM), uveal melanoma (UM), and clear cell renal cell carcinoma (ccRCC). However, there is no personalized therapy for BAP1-mutant cancers. Here, we describe an epigenetic drug library screening to identify small molecules that exert selective cytotoxicity against BAP1 knockout CM cells over their isogenic parental cells. Hit characterization reveals that BAP1 loss renders cells more vulnerable to bromodomain and extraterminal (BET) inhibitor-induced transcriptional alterations, G1/G0 cell cycle arrest and apoptosis. The association of BAP1 loss with sensitivity to BET inhibitors is observed in multiple BAP1-deficient cancer cell lines generated by gene editing or derived from patient tumors as well as immunodeficient xenograft and immunocompetent allograft murine models. We demonstrate that BAP1 deubiquitinase activity reduces sensitivity to BET inhibitors. Concordantly, ectopic expression of RING1A or RING1B (H2AK119 E3 ubiquitin ligases) enhances sensitivity to BET inhibitors. The mechanistic study shows that the BET inhibitor OTX015 exerts a more potent suppressive effect on the transcription of various proliferation-related genes, especially MYC, in BAP1 knockout cells than in their isogenic parental cells, primarily by targeting BRD4. Furthermore, ectopic expression of Myc rescues the BET inhibitor-sensitizing effect induced by BAP1 loss. Our study reveals new approaches to specifically suppress BAP1-deficient cancers, including CM, UM, and ccRCC.

Transcriptome sequencing analysis of primary fibroblasts: a new insight into postoperative abdominal adhesion.

PURPOSE: The specific genes or pathways in fibroblasts responsible for the pathogenesis of postoperative abdominal adhesion (PAA) remain to be elucidated. We aim to provide a new insight into disease mechanisms at the transcriptome level. METHODS: Male Sprague-Dawley rats were used to establish a PAA model. Primary fibroblasts were separated from normal peritoneal tissue (NF) and postoperative adhesion tissue (PF). RNA sequencing was used to analyze the transcriptome in NF and PF. RESULTS: One thousand two hundred thirty-five upregulated and 625 downregulated DEGs were identified through RNA-Seq. A pathway enrichment analysis identified distinct enriched biological processes, among which the most prominent was related to immune and inflammatory response and fibrosis. HE staining and Masson's trichrome staining histologically validated the RNA-Seq results. Six hub genes, ITGAM, IL-1ß, TNF, IGF1, CSF1R and EGFR were further verified by RT-PCR. CONCLUSIONS: Our study revealed the roles of the immune and inflammatory responses and fibrosis in the process of PAA. We also found six hub genes that may be potential therapeutic targets for PPA.

Terahertz magneto-optical response of bismuth-gadolinium-substituted rare-earth garnet film.

We report the magneto-optical Faraday response of bismuth-gadolinium-substituted rare-earth iron garnet at terahertz frequencies ranging from 100 GHz to 1.2 THz. The maximum transmittance of ±45° component is about 60% near the frequency point of 0.63 THz. When the external magnetic field change from -100 mT to +100 mT, the Faraday rotation angle is between -6° and +7.5°. The overall change of ellipticity is relatively small. The maximum value of the Verdet constant is about 260 °/mm/T at 0.1 THz and then gradually decreases to 80 °/mm/T at 1.2 THz. Within the considered frequency range, the thick film exhibits magnetically tunable, non-reciprocal characters and a strong magneto-optical effect within a small external magnetic field at room temperature, which will be widely used for the terahertz isolators, circulators, nonreciprocal phase shifters, and magneto-optical modulators.

Terahertz magneto-optical effect of wafer-scale La: yttrium iron garnet single-crystal film with low loss and high permittivity.

The wafer-scale La:YIG single crystal thick films were fabricated on a three-inch gadolinium gallium garnet (GGG) substrate by liquid phase epitaxy method. The terahertz (THz) optical and magneto-optical properties of La:YIG film were demonstrated by THz time domain spectroscopy (THz-TDS). The results show that a high refractive index of approximately 4.09 and a low absorption coefficient of 10-50 cm-1 from 0.1 to 1.6 THz for this La:YIG film. Moreover, the THz Faraday rotation effect of La:YIG film was measured by the orthogonal polarization detection method in THz-TDS system, which can be actively manipulated by a weak longitudinal magnetic field of up to 0.155 T. With 5 samples stacked together, the Faraday rotation angle varies linearly from -15° to 15°, and the Verdet constant of La:YIG is about 100 °/mm/T within the saturation magnetization. This magneto-optical single crystal thick film with large area shows low loss, high permittivity and strong magneto-optical effect in the THz regime, which will be widely used in magneto-optical polarization conversion, nonreciprocal phase shifter and isolator for THz waves.

Piezoelectricity of single-atomic-layer MoS2 for energy conversion and piezotronics.

The piezoelectric characteristics of nanowires, thin films and bulk crystals have been closely studied for potential applications in sensors, transducers, energy conversion and electronics. With their high crystallinity and ability to withstand enormous strain, two-dimensional materials are of great interest as high-performance piezoelectric materials. Monolayer MoS2 is predicted to be strongly piezoelectric, an effect that disappears in the bulk owing to the opposite orientations of adjacent atomic layers. Here we report the first experimental study of the piezoelectric properties of two-dimensional MoS2 and show that cyclic stretching and releasing of thin MoS2 flakes with an odd number of atomic layers produces oscillating piezoelectric voltage and current outputs, whereas no output is observed for flakes with an even number of layers. A single monolayer flake strained by 0.53% generates a peak output of 15 mV and 20 pA, corresponding to a power density of 2 mW m(-2) and a 5.08% mechanical-to-electrical energy conversion efficiency. In agreement with theoretical predictions, the output increases with decreasing thickness and reverses sign when the strain direction is rotated by 90°. Transport measurements show a strong piezotronic effect in single-layer MoS2, but not in bilayer and bulk MoS2. The coupling between piezoelectricity and semiconducting properties in two-dimensional nanomaterials may enable the development of applications in powering nanodevices, adaptive bioprobes and tunable/stretchable electronics/optoelectronics.

Optical Imaging and Spectroscopic Characterization of Self-Assembled Environmental Adsorbates on Graphene.

Topographic studies using scanning probes have found that graphene surfaces are often covered by micron-scale domains of periodic stripes with a 4 nm pitch. These stripes have been variously interpreted as structural ripples or as self-assembled adsorbates. We show that the stripe domains are optically anisotropic by imaging them using a polarization-contrast technique. Optical spectra between 1.1 and 2.8 eV reveal that the anisotropy in the in-plane dielectric function is predominantly real, reaching 0.6 for an assumed layer thickness of 0.3 nm. The spectra are incompatible with a rippled graphene sheet but would be quantitatively explained by the self-assembly of chainlike organic molecules into nanoscale stripes.

Adiposity and risks of colorectal and small intestine cancer in Chinese adults: a prospective study of 0.5 million people.

BACKGROUND: Uncertainty remains about the associations of adiposity with intestinal cancer in China and by its anatomical subtype. METHODS: The prospective China Kadoorie Biobank recorded 3024 incident cases of colorectal (CRC) and 143 cases of small intestine (SIC) cancer during a 10-year follow-up among 509 568 participants without prior cancer at baseline. Cox regression was used to estimate adjusted hazard ratios (HRs) for specific cancers associated with adiposity. RESULTS: Overall mean body mass index (BMI) was 23.7 kg/m2. BMI was positively associated with CRC (HR per SD 1.10 [95% CI 1.06-1.14]), colon (1.13 [1.07-1.18]), and rectal (1.07 [1.02-1.13]) cancer. For waist circumference, the corresponding HRs per SD were 1.14 (1.10-1.18), 1.18 (1.13-1.24), and 1.11 (1.05-1.16), respectively. The adjusted HRs were somewhat greater in men than women. Adiposity was positively, but non-significantly, associated with SIC risk. CONCLUSIONS: Among relatively lean Chinese adults, adiposity was associated with risks of colon and rectal cancer, with the associations somewhat stronger in men than women.

Hydrogels with precisely controlled integrin activation dictate vascular patterning and permeability.

Integrin binding to bioengineered hydrogel scaffolds is essential for tissue regrowth and regeneration, yet not all integrin binding can lead to tissue repair. Here, we show that through engineering hydrogel materials to promote α3/α5ß1 integrin binding, we can promote the formation of a space-filling and mature vasculature compared with hydrogel materials that promote αvß3 integrin binding. In vitro, α3/α5ß1 scaffolds promoted endothelial cells to sprout and branch, forming organized extensive networks that eventually reached and anastomosed with neighbouring branches. In vivo, α3/α5ß1 scaffolds delivering vascular endothelial growth factor (VEGF) promoted non-tortuous blood vessel formation and non-leaky blood vessels by 10 days post-stroke. In contrast, materials that promote αvß3 integrin binding promoted endothelial sprout clumping in vitro and leaky vessels in vivo. This work shows that precisely controlled integrin activation from a biomaterial can be harnessed to direct therapeutic vessel regeneration and reduce VEGF-induced vascular permeability in vivo.

One-step synthesis, electronic structure, and photocatalytic activity of earth-abundant visible-light-driven FeAl2O4.

The development of inexpensive visible-light-driven photocatalysts is an important prerequisite for realizing the industrial application of photocatalysis technology. In this paper, an earth-abundant FeAl2O4 photocatalyst is prepared via facile solution combustion synthesis. Density functional theory and the scanning Kelvin probe technique are employed to ascertain the positions of the energy bands and the Fermi level. Phenol is taken as a model pollutant to evaluate the photocatalytic activity of FeAl2O4. The scavenger experiment results, ˙OH-trapping fluorescence technique, and electron spin resonance measurements confirm that the superoxide anion radical is the main active species generated in the photocatalytic process, which also further corroborates the proposed electronic structure of FeAl2O4. The degradation experiments and O2 temperature programmed desorption results over various samples verify that the crystallinity degree is a more important factor than the oxygen adsorption ability in determining photocatalytic activity.

Probing Interlayer Interactions in Transition Metal Dichalcogenide Heterostructures by Optical Spectroscopy: MoS2/WS2 and MoSe2/WSe2.

We have applied optical absorption spectroscopy to investigate van der Waals heterostructures formed of pairs of monolayer transition metal dichalcogenide crystals, choosing MoS2/WS2 and MoSe2/WSe2 as test cases. In the heterostructure spectra, we observe a significant broadening of the excitonic transitions compared to the corresponding features in the isolated layers. The broadening is interpreted as a lifetime effect arising from decay of excitons initially created in either layer through charge transfer processes expected for a staggered band alignment. The measured spectral broadening of 20 meV - 35 meV implies lifetimes for charge separation of the near band-edge A and B excitons in the range of 20-35 fs. Higher-lying transitions exhibit still greater broadening.

Graphene plasmon enhanced vibrational sensing of surface-adsorbed layers.

We characterize the influence of graphene nanoribbon plasmon excitation on the vibrational spectra of surface-absorbed polymers. As the detuning between the graphene plasmon frequency and a vibrational frequency of the polymer decreases, the vibrational peak intensity first increases and is then transformed into a region of narrow optical transparency as the frequencies overlap. Examples of this are provided by the carbonyl vibration in thin films of poly(methyl methacrylate) and polyvinylpyrrolidone. The signal depth of the plasmon-induced transparency is found to be 5 times larger than that of light attenuated by the carbonyl vibration alone. The plasmon-vibrational mode coupling and the resulting fields are analyzed using both a phenomenological model of electromagnetically coupled oscillators and finite-difference time-domain simulations. It is shown that this coupling and the resulting absorption enhancement can be understood in terms of near-field electromagnetic interactions.

Exciton binding energy and nonhydrogenic Rydberg series in monolayer WS(2).

We have experimentally determined the energies of the ground and first four excited excitonic states of the fundamental optical transition in monolayer WS_{2}, a model system for the growing class of atomically thin two-dimensional semiconductor crystals. From the spectra, we establish a large exciton binding energy of 0.32 eV and a pronounced deviation from the usual hydrogenic Rydberg series of energy levels of the excitonic states. We explain both of these results using a microscopic theory in which the nonlocal nature of the effective dielectric screening modifies the functional form of the Coulomb interaction. These strong but unconventional electron-hole interactions are expected to be ubiquitous in atomically thin materials.

Valley splitting and polarization by the Zeeman effect in monolayer MoSe2.

We have measured circularly polarized photoluminescence in monolayer MoSe2 under perpendicular magnetic fields up to 10 T. At low doping densities, the neutral and charged excitons shift linearly with field strength at a rate of ∓0.12 meV/T for emission arising, respectively, from the K and K' valleys. The opposite sign for emission from different valleys demonstrates lifting of the valley degeneracy. The magnitude of the Zeeman shift agrees with predicted magnetic moments for carriers in the conduction and valence bands. The relative intensity of neutral and charged exciton emission is modified by the magnetic field, reflecting the creation of field-induced valley polarization. At high doping levels, the Zeeman shift of the charged exciton increases to ∓0.18 meV/T. This enhancement is attributed to many-body effects on the binding energy of the charged excitons.

Infrared-induced adult colloid milium treated with fractionated CO2 laser.

Adult colloid milium is a rare cutaneous deposition disorder that frequently involves areas of chronic sun exposure. The most common clinical presentation exhibits multiple, firm, and amber-colored papules that cluster to form large plaques. Histologically, there are masses of amorphous, eosinophilic material expanding the papillary dermis, and at times extending into the mid-dermis, with adjacent solar elastosis. When this disorder affects the face, disfiguring is of great concern and treatment is often sought. Attempts to safely remove colloid milium are generally unsuccessful. Dermabrasion has been reported to be effective. The present authors present a case with extensive facial colloid milium successfully ablated by the fractionated CO2 laser.

Bond graph modeling and validation of an energy regenerative system for emulsion pump tests.

The test system for emulsion pump is facing serious challenges due to its huge energy consumption and waste nowadays. To settle this energy issue, a novel energy regenerative system (ERS) for emulsion pump tests is briefly introduced at first. Modeling such an ERS of multienergy domains needs a unified and systematic approach. Bond graph modeling is well suited for this task. The bond graph model of this ERS is developed by first considering the separate components before assembling them together and so is the state-space equation. Both numerical simulation and experiments are carried out to validate the bond graph model of this ERS. Moreover the simulation and experiments results show that this ERS not only satisfies the test requirements, but also could save at least 25% of energy consumption as compared to the original test system, demonstrating that it is a promising method of energy regeneration for emulsion pump tests.

Probing symmetry properties of few-layer MoS2 and h-BN by optical second-harmonic generation.

We have measured optical second-harmonic generation (SHG) from atomically thin samples of MoS2 and h-BN with one to five layers. We observe strong SHG from materials with odd layer thickness, for which a noncentrosymmetric structure is expected, while the centrosymmetric materials with even layer thickness do not yield appreciable SHG. SHG for materials with odd layer thickness was measured as a function of crystal orientation. This dependence reveals the rotational symmetry of the lattice and is shown to provide a purely optical method of determining the orientation of crystallographic axes. We report values for the nonlinearity of monolayers and odd-layers of MoS2 and h-BN and compare the variation as a function of layer thickness with a model that accounts for wave propagation effects.