Real-world effectiveness and predictors of super-responders to dupilumab in a Chinese uncontrolled asthma cohort.

Background: Dupilumab has been shown to be effective in clinical trials for moderate-to-severe uncontrolled asthma. However, the efficacy of dupilumab in the real world and the prediction of treatment response have not been well studied in patients with asthma. Objective: To investigate the efficacy of dupilumab and explore predictors of super-responders in a Chinese retrospective cohort. Methods: From January 2021 through December 2022, the patients with uncontrolled asthma who were treated with dupilumab for 4 months were included. Symptom control, type 2 inflammatory biomarkers, and lung function were collected at baseline and follow-up for efficacy assessment. Super-responders were defined as exacerbation-free, off maintenance of oral corticosteroids (mOCS), and with a score of the five-item Asthma Control Questionnaire (ACQ-5) of <0.5. The uni- and multivariable logistic regressions were used to construct predictive models for super-responders based on baseline features. Results: A total of 53 patients were included. After 4 months treatment, the median (interquartile range [IQR]) ACQ-5 score decreased from 1.8 (1.6-2.4) to 0.4 (0.2-0.8) (p < 0.001), the median (IQR) number of exacerbations, from 0.0 (0.0-1.0) to 0.0 (0.0-0.0) (p = 0.005). The median (IQR) dose of mOCS (prednisone equivalent) decreased from 15.0 mg/day (8.8-22.5 mg/day) to 2.5 mg/day (0.0-10.0 mg/day) (p = 0.008) in nine patients who were receiving mOCS. All efficacy assessment parameters, including sputum eosinophil were significantly improved, while blood eosinophil count did not decline (530 cells/mm³ [300-815 cells/mm³] versus 560 cells/mm³ [220-938 cells/mm³], p = 0.710). After taking dupilumab, 25 of 53 patients (47.2%) achieved a super-response. The age of onset < 42 years (odds ratio [OR] 7.471 [95% confidence interval {CI}, 1.286-43.394) and the baseline fractional exhaled nitric oxide (FeNO) of 25-50 ppb (OR 35.038 [95% CI, 3.104-395.553]) predicted super-responders, which showed a C-index of 0.822 (95% CI, 0.697-0.947). Conclusion: Dupilumab significantly improved symptom control, type 2 inflammatory markers, and lung function in Chinese patients with uncontrolled asthma. Airway eosinophils, rather than blood eosinophils, can be a reliable indicator of therapeutic efficacy. The early-onset asthma as well as the medium-high level of baseline FeNO contributed to the prediction of super-responders.

Dielectrophoresis-electrophoresis transition during the photovoltaic manipulation of water microdroplets on LiNbO3:Fe platform.

The abrupt behaviors of microdroplets during the LN-based photovoltaic manipulation may cause the transient instability and even failure of the microfluidic manipulation. In this paper, we perform a systematical analysis on the responses of water microdroplets to laser illumination on both naked and PTFE-coated LN:Fe surface, and find that the abrupt repulsive behaviors of the microdroplets are due to the electrostatic transition from the dielectrophoresis (DEP) to electrophoresis (EP) mechanism. Charging of the water microdroplets through the Rayleigh jetting from electrified water/oil interface is suggested as the cause of the DEP-EP transition. Fitting the kinetic data of the microdroplets to the models describing the motion of the microdroplets under the photovoltaic field yields the charging amount depending on the substrate configuration (∼1.7 × 10-11 and 3.9 × 10-12 C on the naked and PTFE-coated LN:Fe substrates), and also reveals the dominance of the EP mechanism in the co-existence of the DEP and EP mechanisms. The outcome of this paper will be quite important to the practicalization of the photovoltaic manipulation in LN-based optofluidic chips.

Hydrophobic-substrate based water-microdroplet manipulation through the long-range photovoltaic interaction from a distant LiNbO3:Fe crystal.

Development of photovoltaic water-microdroplet manipulation using LN:Fe crystals has to meet the requirement of the hybrid and heating-avoided design of biological lab-on-chips. To fulfill this, we demonstrate a successful manipulation of a water microdroplet on a hydrophobic substrate by utilizing the long-range photovoltaic interaction from a distant LN:Fe crystal (see Visualization 1). The maximal manipulation distance (MMD) is found to be dependent on the laser-illumination intensity at the LN:Fe crystal and it can be tuned up to a sub-centimeter level (∼4 mm). Basing on the two-center model of light-induced charge transport in the LN:Fe crystal, we establish an analytic model to describe the force balance during the microdroplet manipulation under a long-range photovoltaic interaction. Either shortening the manipulation distance or increasing the illumination intensity can enhance the photovoltaic interaction and increase the velocity of the microdroplet being manipulated. An abrupt shape change followed by a fast repelling movement of the water microdroplet is observed under a strong photovoltaic interaction (see Visualization 2).

Efficient Broadband Yellow-Green Emission of Vacancy Halide Double Perovskites Through the Ion-Exchanged Strategy.

Broadband high-efficiency luminescent materials have become a hot spot in lead-free perovskite research. There are relatively few broadband yellow-green phosphors with both ultraviolet and blue excitation ranges, which make them more suitable for phosphor-converted white LEDs. Through the ion-exchanged strategy, Cs2Hf1-xTexCl6 (CH1-xTxC) vacancy halide double perovskites were successfully prepared at room temperature. Using different excitation ranges of CH1-xTxC, two types of high-quality white LEDs are obtained. By combining density functional theory calculations and experiments, it is proved that this bright broadband yellow-green emission (photoluminescence quantum yield of 83.46%) is not only derived from the ion transitions of Te4+ but also exhibits the inherent characteristics of self-trapped exciton emission. Our results not only broaden the application fields of lead-free halide perovskites but also provide further insights into the luminescence mechanism.

Internal Cylinder Identification Based on Different Transmission of Longitudinal and Shear Ultrasonic Waves.

We have built a Fizeau fiber interferometer to investigate the internal cylindrical defects in an aluminum plate based on laser ultrasonic techniques. The ultrasound is excited in the plate by a Q-switched Nd:YAG laser. When the ultrasonic waves interact with the internal defects, the transmitted amplitudes of longitudinal and shear waves are different. The experimental results show that the difference in transmission amplitudes can be attributed to the high frequency damping of internal cylinders. When the scanning point is close to the internal defect, the longitudinal waves attenuate significantly in the whole defect area, and their amplitude is always smaller than that of shear waves. By comparing the transmitted amplitudes of longitudinal and shear waves at different scanning points, we can achieve a C scan image of the sample to realize the visual inspection of internal defects. Our system exhibits outstanding performance in detecting internal cylinders, which could be used not only in evaluating structure cracks but also in exploring ultrasonic transmission characteristics.

Photovoltaic splitting of water microdroplets on a y-cut LiNbO3:Fe crystal coated with oil-infused hydrophobic insulating layers.

We demonstrate the successful photovoltaic splitting of water microdroplets on a $y$y-cut ${{\rm LiNbO}_3}:{\rm Fe}$LiNbO3:Fe substrate coated with an oil-infused hydrophobic layer. The temporal evolution of the microdroplet contact angle upon a central illumination and the distinct behaviors of two sub-droplets during a following boundary illumination reveal that both electrowetting and electroosmotic effects induced by the dipolar photovoltaic potential on the substrate contribute to the water microdroplet splitting. The reciprocal relationship between the splitting time and the illumination intensity verifies the inherent photovoltaic nature of the water microdroplet splitting. The splitting time is found to be linearly dependent on the initial microdroplet size. These points are quite important to the practicalization of lithium niobate (LN)-based microfluidic chips in the biological field.

All-optical splitting of dielectric microdroplets by using a y-cut-LN-based anti-symmetrical sandwich structure.

We demonstrate an all-optical active mode of dielectric microdroplet splitting in a sandwich structure consisting of two anti-symmetrical y-cut LN:Fe substrates. The dynamic process of the microdroplet splitting and the simulation of the electrostatic interaction inside the sandwich gap show that the combination of two anti-symmetrical substrates are capable to provide a sufficient dielectrophoretic force and to reduce the unbalance of the drag forces for a stable and efficient splitting of the microdroplet. The dependences of the splitting time on the illumination intensity and the initial microdroplet size are also studied, and the results show that the microdroplet splitting process is fully governed by the establishment of the superposed photovoltaic field inside the sandwich gap. A key ratio Er/E0, representing the microdroplet splitting difficulty for a given sandwich structure, is found linearly dependent on the initial microdroplet size. These points are quite important to the integration of splitting functionality on the LN-based microfluidic chip.

Visible-light-assisted condensation of ultrasonically atomized water vapor on LiNbO3:Fe crystals.

Optically massive trapping of the moisture in the air into an adjacent surface is a potential technique in the fields of bacterial adhesion and microfluidic generation, which is quite important to the development of LN-based biological lab-on-chips. Here we demonstrate on a LiNbO3:Fe substrate the visible-light-assisted condensation of the water vapor in a flowing stream created by an ultrasonic atomizer. Through analyzing the dynamic processes of the visible-light-assisted water condensation at different illumination intensities, it is found that the extent of the water condensation, the bending angle of water vapor trails and the interaction range of the condensation effect are highly dependent on the illumination intensity. According to these findings and the simulated trajectories of the water vapor stream at different illumination intensities, we propose that this visible-light-assisted water condensation is an aggregation process of tiny water droplets driven by the dielectrophoretic interaction of inhomogeneous photovoltaic field and also an electrostatic screening course of photovoltaic charges through the charged evaporation of condensed water. The prolonged condensation of water vapor after a high-intensity illumination and that of oil vapor at a super-low evaporation rate are also studied, and the agreement between the simulation and experimental results reinforces the above mechanism. The reported technique, employing the inexpensive, safe-for-cell visible laser beam, is quite convenient for the controllable generation of various biological microdroplets, and thus it is promising for the microfluidic functionality integration of LN-based biological lab-on-chips.

Direct laser writing combined with a phase-delay probe.

We develop on lithium niobate crystals a photorefractive direct-laser-writing approach, in which we combine in one beam both direct writing and phase-delay probing functionalities to extract the in situ information of the refractive index or the electrostatic field. The phase-delay signal, predicted well by the photorefractive theory, is used as feedback for tuning the exposure time or scanning speed of the focused laser in order to control the refractive index change (Δn) at single points and scanning lines. Different features found in creating Δn at the points and lines are explained by the different photorefractive responses in the two cases.

Meconium peritonitis due to fetal appendiceal perforation: two case reports and a brief review of the literature.

BACKGROUND: Meconium peritonitis is an infrequent congenital disease usually caused by perforation of the fetal digestive tract. Meconium peritonitis resulting from intrauterine appendiceal perforation has been rarely reported and is often overlooked during pregnancy. We herein report two cases of fetal appendiceal perforation. CASE PRESENTATION: Two neonates were found to have intestinal distension and gradually increasing ascites antenatally. After birth, diagnostic abdominal punctures revealed meconium peritonitis. Urgent surgery showed both neonates had developed gangrenous appendicitis in utero. Pathological examination supported the diagnosis of fetal appendiceal perforation in both neonates, and one also had deformity of cecal duplication. In the present report, we also review the presentation, diagnosis, pathology, management, and recent literature of fetal appendiceal perforation. CONCLUSION: Meconium peritonitis due to fetal appendiceal perforation is extremely rare, and preoperative diagnosis is almost impossible. However, clinicians should be aware of abnormal gastrointestinal manifestations in the fetus during the antenatal examination. For neonates with severe meconium peritonitis, an early operation with careful intraoperative exploration is necessary.

Gastroschisis in monochorionic male twins.

We report a case of gastroschisis in male twins. Both twins were preterm and low birth weight, with intestinal malrotation; they were diagnosed by antenatal ultrasound at 20 weeks of gestation. Immediately after delivery, they underwent evaluation and early surgical one-stage repair under anesthesia. One of the twins was found to have duodenal perforation at laparotomy, at the horizontal part near Treitz ligament. Both twins stayed in hospital for 30 days and were in good health at discharge.

Photo-assisted splitting of dielectric microdroplets in a LN-based sandwich structure.

We demonstrate an active and controllable photo-assisted splitting of dielectric microdroplets inside a LiNbO3-based sandwich structure by utilizing the pyroelectric and photovoltaic effects of LiNbO3 crystals. Basing on electrostatic simulation results, the mechanism of the photo-assisted splitting is explained; meanwhile, the microdoplet pre-polarizing and the inclined electrostatic force induced by the photovoltaic charges inside the sandwich structure are emphasized. We also study the dependence of the splitting part size on the substrate temperature variation, the irradiation intensity, and the duration. Featured dependence is found to follow the theoretical curve predicted by the compensation between the photo-excited and bound surface charges.

Photo-assisted proton exchange and chemical etching on Fe-doped lithium niobate crystals.

We report the photo-assisted proton exchange and chemical etching on Fe-doped LiNbO(3) crystals. Selective proton exchange and chemical etching are realized through the 455nm-laser irradiation on the crystal surface in pyrophosphoric acid. Optical microscopy and Micro-IR spectroscopy analysis show that the hydrogen incorporation is confined spatially by the laser irradiation. Moreover, under the laser irradiation, + z surface is found to be more easily etched than -z surface. This unexpected etching anisotropy is attributed to the photogalvanic effect of the crystal.

Atomically precise doping of monomanganese ion into coreless supertetrahedral chalcogenide nanocluster inducing unusual red shift in Mn(2+) emission.

We report a simple and yet effective method to introduce Mn(2+) ions into semiconducting nanoclusters with atomically precise control. Our method utilizes one type of micrometer-sized crystals, composed of well-defined isolated supertetrahedral chalcogenide nanoclusters (∼2 nm, [Cd6In28S52(SH)4]) whose core metal site is unoccupied in as-synthesized pristine form. This unique model structure with vacant core site makes it possible to achieve ordered distribution of Mn(2+) dopants, and at the same time effectively preclude the formation of Mn(2+) clusters in the host matrix. A two-step synthesis strategy is applied to realize an atomically precise doping of Mn(2+) ion into the core site of the nanoclusters, and to achieve uniform distribution of Mn(2+) dopants in the crystal lattice. The PL, X-ray photoelectron (XPS), as well as the electron paramagnetic resonance (EPR) spectra reveal the successful incorporation of Mn(2+) ion into the core site of the nanocluster. Different from the pristine host material with weak green emission (∼490 nm), the Mn(2+)-doped material shows a strong red emission (630 nm at room temperature and 654 nm at 30 K), which is significantly red-shifted relative to the orange emission (∼585 nm) observed in traditional Mn(2+)-doped II-VI semiconductors. Various experiments including extensive synthetic variations and PL dynamics have been performed to probe the mechanistic aspects of synthesis process and resultant unusual structural and PL properties. The quaternary semiconductor material reported here extends the emission window of Mn(2+)-doped II-VI semiconductor from yellow-orange to red, opening up new opportunities in applications involving photonic devices and bioimaging.

Effect of copper toxicity on root morphology, ultrastructure, and copper accumulation in Moso bamboo (Phyllostachys pubescens).

A hydroponic culture experiment was conducted to study the effect of copper toxicity on root morphology, ultrastructure, and copper accumulation in Moso bamboo (Phyllostachys pubescens). Root ultrastructure of Moso bamboo was studied by transmission electron microscopy and scanning electron microscopy. Application of 200 µM Cu resulted in an accumulation of 810 mg kg(-1) dry weight and 91 mg kg(-1) dry weight Cu in roots and shoots, respectively. The majority of the plants did not survive the application of 400 µM Cu. Biomass production declined consistently with application of each additional increment of Cu. Root growth was more severely inhibited than shoot growth. Cu adversely affected the root morphology of the plants, however, root surface area and number of root tips increased slightly at low levels of Cu. Root cell ultrastructure and organelles changed significantly under Cu stress, in particular, cell walls, mitochondria, and xylem parenchyma were affected.

Food emulsions stabilized by proteins and emulsifiers: A review of the mechanistic explorations.

The stability of food emulsions is the basis for other properties. During their production and processing, emulsions tend to become unstable due to their thermodynamic instability, and it is usually necessary to add emulsifiers and proteins to stabilize emulsions. It becomes crucial to study the intrinsic mechanisms of emulsifiers and proteins and their joint stabilization of food emulsions. This paper summarizes the research on intrinsic mechanisms of food emulsions stabilized by emulsifiers and proteins in recent years. The destabilization and stabilization of emulsions are related to the added surfactants. The properties, type, and concentration of emulsifiers determine the stability of emulsions, and the emulsifiers can be classified into different types (e.g., ionic or nonionic, solid or liquid) according to their properties and sources. The physicochemical properties of proteins (e.g., spatial conformation, hydrophobicity) and the composition of proteins can also determine the stability of emulsions, and emulsions stabilized by emulsifiers and proteins together not only depend on these factors but also have a great relationship with the mutual combination and competition between the two. The instability and stability of emulsions are related to factors such as interfacial interaction forces, the rheological nature of the interface, and the added surfactant.

Metformin targets c-MYC oncogene to prevent prostate cancer.

UNLABELLED: Prostate cancer (PCa) is the second leading cause of cancer-related death in American men and many PCa patients develop skeletal metastasis. Current treatment modalities for metastatic PCa are mostly palliative with poor prognosis. Epidemiological studies indicated that patients receiving the diabetic drug metformin have lower PCa risk and better prognosis, suggesting that metformin may have antineoplastic effects. The mechanism by which metformin acts as chemopreventive agent to impede PCa initiation and progression is unknown. The amplification of c-MYC oncogene plays a key role in early prostate epithelia cell transformation and PCa growth. The purpose of this study is to investigate the effect of metformin on c-myc expression and PCa progression. Our results demonstrated that (i) in Hi-Myc mice that display murine prostate neoplasia and highly resemble the progression of human prostate tumors, metformin attenuated the development of prostate intraepithelial neoplasia (PIN, the precancerous lesion of prostate) and PCa lesions. (ii) Metformin reduced c-myc protein levels in vivo and in vitro. In Myc-CaP mouse PCa cells, metformin decreased c-myc protein levels by at least 50%. (iii) Metformin selectively inhibited the growth of PCa cells by stimulating cell cycle arrest and apoptosis without affecting the growth of normal prostatic epithelial cells (RWPE-1). (iv) Reduced PIN formation by metformin was associated with reduced levels of androgen receptor and proliferation marker Ki-67 in Hi-Myc mouse prostate glands. Our novel findings suggest that by downregulating c-myc, metformin can act as a chemopreventive agent to restrict prostatic neoplasia initiation and transformation. SUMMARY: Metformin, an old antidiabetes drug, may inhibit prostate intraepithelial neoplasia transforming to cancer lesion via reducing c-MYC, an 'old' overexpressed oncogene. This study explores chemopreventive efficacy of metformin in prostate cancer and its link to cMYC in vitro and in vivo.

Water oxidation using a cobalt monolayer prepared by underpotential deposition.

Development of electrocatalysts for the conversion of water to dioxygen is important in a variety of chemical applications. Despite much research in this field, there are still several fundamental issues about the electrocatalysts that need to be resolved. Two such problems are that the catalyst mass loading on the electrode is subject to large uncertainties and the wetted surface area of the catalyst is often unknown and difficult to determine. To address these topics, a cobalt monolayer was prepared on a gold electrode by underpotential deposition and used to probe its efficiency for the oxidation of water. This electrocatalyst was characterized by atomic force microscopy, grazing-incidence X-ray diffraction, and X-ray photoelectron spectroscopy at various potentials to determine if changes occur on the surface during catalysis. An enhancement of current was observed upon addition of PO4(3-) ions, suggesting an effect from surface-bound ligands on the efficiency of water oxidation. At 500 mV overpotential, current densities of 0.20, 0.74, and 2.4 mA/cm(2) for gold, cobalt, and cobalt in PO4(3-) were observed. This approach thus provided electrocatalysts whose surface areas and activity can be accurately determined.

A chemically-responsive nanojunction within a silver nanowire.

The formation of a nanometer-scale chemically responsive junction (CRJ) within a silver nanowire is described. A silver nanowire was first prepared on glass using the lithographically patterned nanowire electrodeposition method. A 1-5 nm gap was formed in this wire by electromigration. Finally, this gap was reconnected by applying a voltage ramp to the nanowire resulting in the formation of a resistive, ohmic CRJ. Exposure of this CRJ-containing nanowire to ammonia (NH(3)) induced a rapid (<30 s) and reversible resistance change that was as large as ΔR/R(0) = (+)138% in 7% NH(3) and observable down to 500 ppm NH(3). Exposure to water vapor produced a weaker resistance increase of ΔR/R(0,H(2)O) = (+)10-15% (for 2.3% water) while nitrogen dioxide (NO(2)) exposure induced a stronger concentration-normalized resistance decrease of ΔR/R(0,NO(2)) = (-)10-15% (for 500 ppm NO(2)). The proposed mechanism of the resistance response for a CRJ, supported by temperature-dependent measurements of the conductivity for CRJs and density functional theory calculations, is that semiconducting p-type Ag(x)O is formed within the CRJ and the binding of molecules to this Ag(x)O modulates its electrical resistance.

Investigation of Optoelectronic Functional Crystals: Crystal Growth, Properties and Applications.

Optoelectronic functional crystals facilitate the conversion of light and electricity, inspiring breakthroughs in the fabrication of optoelectronic devices [...].