Genomic Island-Mediated Horizontal Transfer of the Erythromycin Resistance Gene erm(X) among Bifidobacteria.

Antibiotic resistance is a serious medical issue driven by antibiotic misuse. Bifidobacteria may serve as a reservoir for antibiotic resistance genes (ARGs) that have the potential risk of transfer to pathogens. The erythromycin resistance gene erm(X) is an ARG with high abundance in bifidobacteria, especially in Bifidobacterium longum species. However, the characteristics of the spread and integration of the gene erm(X) into the bifidobacteria genome are poorly understood. In this study, 10 tetW-positive bifidobacterial strains and 1 erm(X)-positive bifidobacterial strain were used to investigate the transfer of ARGs. Conjugation assays found that the erm(X) gene could transfer to five other bifidobacterial strains. Dimethyl sulfoxide (DMSO) and vorinostat significantly promoted the transfer of the erm(X) from strain Bifidobacterium catenulatum subsp. kashiwanohense DSM 21854 to Bifidobacterium longum subsp. suis DSM 20211. Whole-genome sequencing and comparative genomic analysis revealed that the erm(X) gene was located on the genomic island BKGI1 and that BKGI1 was conjugally mobile and transferable. To our knowledge, this is the first report that a genomic island-mediated gene erm(X) transfer in bifidobacteria. Additionally, BKGI1 is very unstable in B. catenulatum subsp. kashiwanohense DSM 21854 and transconjugant D2TC and is highly excisable and has an intermediate circular formation. In silico analysis showed that the BKGI1 homologs were also present in other bifidobacterial strains and were especially abundant in B. longum strains. Thus, our results confirmed that genomic island BKGI1 was one of the vehicles for erm(X) spread. These findings suggest that genomic islands play an important role in the dissemination of the gene erm(X) among Bifidobacterium species. IMPORTANCE Bifidobacteria are a very important group of gut microbiota, and the presence of these bacteria has many beneficial effects for the host. Thus, bifidobacteria have attracted growing interest owing to their potential probiotic properties. Bifidobacteria have been widely exploited by the food industry as probiotic microorganisms, and some species have a long history of safe use in food and feed production. However, the presence of antibiotic resistance raises the risk of its application. In this study, we analyzed the transfer of the erythromycin resistance gene erm(X) and revealed that the molecular mechanism behind the spread of the gene erm(X) was mediated by genomic island BKGI1. To the best of our knowledge this is the first report to describe the transfer of the gene erm(X) via genomic islands among bifidobacteria. This may be an important way to disseminate the gene erm(X) among bifidobacteria.

Modeling of a Soft-Rigid Gripper Actuated by a Linear-Extension Soft Pneumatic Actuator.

Soft robot has been one significant study in recent decades and soft gripper is one of the popular research directions of soft robot. In a static gripping system, excessive gripping force and large deformation are the main reasons for damage of the object during the gripping process. For achieving low-damage gripping to the object in static gripping system, we proposed a soft-rigid gripper actuated by a linear-extension soft pneumatic actuator in this study. The characteristic of the gripper under a no loading state was measured. When the pressure was >70 kPa, there was an approximately linear relation between the pressure and extension length of the soft actuator. To achieve gripping force and fingertip displacement control of the gripper without sensors integrated on the finger, we presented a non-contact sensing method for gripping state estimation. To analyze the gripping force and fingertip displacement, the relationship between the pressure and extension length of the soft actuator in loading state was compared with the relationship under a no-loading state. The experimental results showed that the relative error between the analytical gripping force and the measured gripping force of the gripper was ≤2.1%. The relative error between analytical fingertip displacement and theoretical fingertip displacement of the gripper was ≤7.4%. Furthermore, the low damage gripping to fragile and soft objects in static and dynamic gripping tests showed good performance of the gripper. Overall, the results indicated the potential application of the gripper in pick-and-place operations.

Piezoelectric Shunt Stiffness in Rhombic Piezoelectric Stack Transducer with Hybrid Negative-Impedance Shunts: Theoretical Modeling and Stability Analysis.

Negative-capacitance shunted piezoelectric polymer was investigated in depth due to its considerable damping effect. This paper discusses the novel controlled stiffness performance from a rhombic piezoelectric stack transducer with three hybrid negative-impedance shunts, namely, negative capacitance in series with resistance, negative capacitance in parallel with resistance, and negative inductance/negative capacitance (NINC) in series with resistance. An analytical framework for establishing the model of the coupled system is presented. Piezoelectric shunt stiffness (PSS) and piezoelectric shunt damping (PSD) are proposed to analyze the stiffness and damping performances of the hybrid shunts. Theoretical analysis proves that the PSS can produce both positive and negative stiffness by changing the negative capacitance and adjustable resistance. The Routh-Hurwitz criterion and the root locus method are utilized to judge the stability of the three hybrid shunts. The results point out that the negative capacitance should be selected carefully to sustain the stability and to achieve the negative stiffness effect of the transducer. Furthermore, negative capacitance in parallel with resistance has a considerably better stiffness bandwidth and damping performance than the other two shunts. This study demonstrates a novel electrically controlled stiffness method for vibration control engineering.

A Novel PZT Pump with Built-in Compliant Structures.

Different to the traditionally defined valved piezoelectric (PZT) pump and valveless PZT pump, two groups of PZT pumps with built-in compliant structures-with distances between the free ends of 0.2 mm (Group A) and 0 mm (Group B)-were designed, fabricated, and experimentally tested. This type of pump mainly contains a chamber 12 mm in diameter and 1.1 mm in height, a PZT vibrator, and two pairs of compliant structures arranged on the flowing channel. The flow-resistance differences between these two groups of PZT pumps were theoretically and experimentally verified. The relationships between the amplitude, applied voltage and frequency of the PZT vibrators were obtained experimentally, with results illustrating that the amplitude linearly and positively correlates with the voltage, while nonlinearly and negatively correlating to the frequency. The flow rate performance of these two groups was experimentally tested from 110⁻160 Vpp and 10⁻130 Hz. Results showed that the flow rate positively correlates to the voltage, and the optimum flow rate frequency centers around 90 Hz for Group A and 80 Hz for Group B, respectively. The flow rate performances of Group B were further measured from 60⁻100 Hz and 170⁻210 Vpp, and obtained optimal flow rates of 3.6 mL/min at 210 Vpp and 80 Hz when ignoring the siphon-caused backward flow rate. As the compliant structures are not prominently limited by the channel's size, and the pump can be minimized by Micro-electromechanical Systems (MEMS) processing methods, it is a suitable candidate for microfluidic applications like closed-loop cooling systems and drug delivery systems.

Genome-wide identification and expression analysis of the CaLAX and CaPIN gene families in pepper (Capsicum annuum L.) under various abiotic stresses and hormone treatments.

Auxin plays key roles in regulating plant growth and development as well as in response to environmental stresses. The intercellular transport of auxin is mediated by the following four gene families: ATP-binding cassette family B (ABCB), auxin resistant1/like aux1 (AUX/LAX), PIN-formed (PIN), and PIN-like (PILS). Here, the latest assembled pepper (Capsicum annuum L.) genome was used to characterise and analyse the CaLAX and CaPIN gene families. Genome-wide investigations into these families, including chromosomal distributions, phytogenic relationships, and intron/exon structures, were performed. In total, 4 CaLAX and 10 CaPIN genes were mapped to 10 chromosomes. Most of these genes exhibited varied tissue-specific expression patterns assessed by quantitative real-time PCR. The expression profiles of the CaLAX and CaPIN genes under various abiotic stresses (salt, drought, and cold), exogenous phytohormones (IAA, 6-BA, ABA, SA, and MeJA), and polar auxin transport inhibitor treatments were evaluated. Most CaLAX and CaPIN genes were altered by abiotic stress at the transcriptional level in both shoots and roots, and many CaLAX and CaPIN genes were regulated by exogenous phytohormones. Our study helps to identify candidate auxin transporter genes and to further analyse their biological functions in pepper development and in its adaptation to environmental stresses.

Experimental Verification of the Pumping Effect Caused by the Micro-Tapered Hole in a Piezoelectric Atomizer.

In this study, we examined the use of a dynamic micro-tapered hole as a micro-scale tapered flow tube valveless piezoelectric pump. Firstly, we obtained photographs of a micro-tapered hole by using an environmental scanning electron microscope (ESEM). Then, we explained the pump effect of the micro-tapered hole, and derived the atomization rate equation. Furthermore, we reported an atomization rate measurement experiment that eliminated the atomization caused by a pressure increase, and demonstrated that a change in the volume of a micro-tapered hole could produce atomization. The experimental results indicate that, under the same voltage, the forward atomization rate is much higher than the reverse atomization rate and that the atomization rate increases with the micro-tapered hole volume. The experimental results show that the atomization of the micro-tapered aperture atomizer is caused by its pumping effect. Moreover, the flow resistance and volume of the micro-tapered hole can affect the atomization rate.

Experimental Study on the Performance of Hydraulic Vibration Assisted Broaching (HVAB) Based on Piezoelectric Sensors.

In order to improve the keyway broaching process and verify the feasibility of vibration-assisted broaching process, an experimental study on a novel hydraulic vibration assisted broaching (HVAB) system with double-valve electro-hydraulic exciter (DVEHE) is proposed in this paper. The performances of HVAB at different excitation frequencies were compared from three aspects: (a) the cutting force under the different vibration frequencies, (b) the surface roughness of the workpiece, and (c) the flank face wear of the tool. For precision on-line measurement of larger broaching forces, four piezoelectric sensors were fixed on the broaching machine. The experimental results show that HVAB can effectively improve the performance of the broaching process, approximately reduce the broaching force by as much as 9.7% compared to conventional broaching (CB) and improve the surface quality of workpiece. Some explanations are offered to support the observations.

Evaluation of Streptococcus thermophilus IFFI 6038 Microcapsules Prepared Using an Ultra-fine Particle Processing System.

Microencapsulation technology has the potential to protect probiotics and to deliver them to the gut, and extrusion is one of the most commonly used methods. However, the rather large diameters of 1~5 mm produced tend to cause oral grittiness and result in low compliance. In this article, Streptococcus thermophilus IFFI 6038 (IFFI 6038) microcapsules were prepared using an ultra-fine particle processing system (UPPS) previously developed by this research group. IFFI 6038 suspension was pumped by a peristaltic pump to the feeding inlet nozzle and then dispersed into micro-droplets by a rotating disk, followed by solidification. Trehalose (16%) was used as a cryoprotectant to protect IFFI 6038 from damage by lyophilization used in the process. Alginate (3%) resulted in IFFI 6038 microcapsules with a median particle diameter (d 50) of 29.32 ± 0.12 µm and a span value of 1.00 ± 0.02, indicating uniform particle size distribution. To evaluate the potential of microencapsulation in protecting IFFI 6038 from the gastric conditions, the viable counts of IFFI 6038 following incubation of IFFI 6038 microcapsules in simulated gastric juices for 120 min were determined and compared with those of free IFFI 6038. The stability of microencapsulated IFFI 6038 upon storage for 3 months at 4°C and 25°C, respectively, was also determined. The results showed that microcapsules prepared by UPPS protected IFFI 6038 from gastric conditions. The results from a rat diarrhea model showed that microcapsules prepared by the UPPS method were able to effectively improve the diarrhea conditions in rats.

Robust laser stripe extraction for three-dimensional reconstruction based on a cross-structured light sensor.

Cross-structured light sensor architecture for 3D reconstruction was established. An improved center of mass method was proposed for laser stripe extraction. For each initial laser stripe center point, the center of mass method was performed along the normal direction that was calculated using the Hessian matrix. The normal directions can be used to divide the laser stripe center points into two categories. Laser stripe extraction experiments showed that the proposed method is fast and robust. 3D reconstruction of a cylinder was used to analyze reconstruction accuracy, with relative accuracy of less than 0.15 mm. 3D reconstruction of a shoe last showed that cross-structured light sensors can obtain more abundant information than single-structured light sensors.

Ocular Cubosome Drug Delivery System for Timolol Maleate: Preparation, Characterization, Cytotoxicity, Ex Vivo, and In Vivo Evaluation.

Glaucoma is an ocular disease featuring increased intraocular pressure (IOP) and its primary treatment strategy is to lower IOP by medication. Current ocular drug delivery in treating glaucoma is confronting a variety of challenges, such as low corneal permeability and bioavailability due to the unique anatomical structure of the human eye. To tackle these challenges, a cubosome drug delivery system for glaucoma treatment was constructed for timolol maleate (TM) in this study. The TM cubosomes (liquid crystalline nanoparticles) were prepared using glycerol monooleate and poloxamer 407 via high-pressure homogenization. These constructed nanoparticles appeared spherical using transmission electron microscopy and had an average particle size of 142 nm, zeta potential of -6.27 mV, and over 85% encapsulation efficiency. Moreover, using polarized light microscopy and small-angle X-ray scattering (SAXS), it was shown that the TM cubosomes have cubic liquid crystalline D-type (Pn3m) structure, which provides good physicochemical stability and high encapsulation efficiency. Ex vivo corneal permeability experiments showed that the total amount of TM cubosomes penetrated was higher than the commercially available eye drops. In addition, in vivo studies revealed that TM cubosomes reduced the IOP in rabbits from 27.8∼39.7 to 21.4∼32.6 mmHg after 1-week administration and had a longer retention time and better lower-IOP effect than the commercial TM eye drops. Furthermore, neither cytotoxicity nor histological impairment in the rabbit corneas was observed. This study suggests that cubosomes are capable of increasing the corneal permeability and bioavailability of TM and have great potential for ocular disease treatment.

Bidirectional causality between idiopathic sudden sensorineural hearing loss and depression: a Mendelian randomization study.

Idiopathic Sudden Sensorineural Hearing Loss (ISSHL) is a sudden onset, unexplained sensorineural hearing loss. Depression is a common mental disorder and a leading cause of disability. Here, We used a two-sample Mendelian randomization approach using pooled statistics from genome-wide association studies of ISSHL (1491 cases, 196,592 controls) and depression (23,424 cases, 192,220 controls) in European populations. This study investigated the bidirectional relationship between single nucleotide polymorphisms associated with depression and ISSHL using inverse variance weighting.Additional sensitivity analyses, such as Mendelian randomization-Egger (MR-Egger), weighted median estimates, and leave-one-out analysis, were performed to assess the reliability of the findings. Significant causal association between genetic susceptibility to ISSHL and depression in a random-effects IVW approach (OR = 1.037, 95% CI = 1.004-1.072, P = 0.030). In contrast, genetic depression was not risk factors for ISSHL (OR = 1.134, 95% CI = 0.871-1.475, P = 0.350). After validation by different MR methods and the sensitivity analysis, all of the above results are consistent. The evidence we have gathered suggests a causal relationship between ISSHL and depression. The presence of the former induces or further exacerbates the latter, whereas a similar situation does not exist when the latter is an influencing factor.

Modelling the controlled drug release of push-pull osmotic pump tablets using DEM.

The push-pull osmotic pump tablet is a promising drug delivery approach, offering advantages over traditional dosage forms in achieving consistent and predictable drug release rates. In the current study, the drug release process of push-pull osmotic pump tablets is modelled for the first time using the discrete element method (DEM) incorporated with a microscopic diffusion-induced swelling model. The effects of dosage and formulation design, such as delivery orifice size, drug-to-polymer ratio, tablet surface curvature, friction between particles and cohesion of polymer particles, on the drug release performance are systematically analysed. Numerical results reveal that an enlarged delivery orifice significantly increases both the total drug release and the drug release rate. Moreover, the larger the swellable particle component in the tablet, the higher the drug release rate. Furthermore, the tablet surface curvature is found to affect the drug release profile, i.e. the final drug release percentage increases with the increasing tablet surface curvature. It is also found that the drug release rate could be controlled by adjusting the inter-particle friction and the cohesion of polymer particles in the formulation. This DEM study offers valuable insights into the mechanisms governing drug release in push-pull osmotic pump tablets.

An experimental study on flow behaviour in suction filling of pharmaceutical powders.

Die filling is a crucial step in the pharmaceutical tablet manufacturing process. For industrial-scale production using rotary presses, suction filling is typically employed due to its significant efficiency advantages over gravity filling. Despite its widespread use, our understanding of the suction filling process remains limited. Specifically, there is insufficient comprehension of how filling performance is influenced by factors such as suction velocity, filling velocity, and the properties of the powder materials. Building on our previous research, this study aims to further investigate the effects of powder properties and process parameters (e.g., filling velocity, suction velocity, fill depth) on suction filling behaviour. A systematic experimental investigation was conducted using a model suction filling system, considering both cohesive and free-flowing pharmaceutical powders. The effect of fill depth on the suction filling of these powders was examined at different filling and suction velocities. The results demonstrate that two distinctive flow regimes in suction filling can be identified: slow filling and fast filling. These regimes are delineated by a critical filling-to-suction velocity ratio. In the slow filling regime, the filling-to-suction velocity ratio is lower than the critical ratio, meaning that the filling phase is slower than the suction phase. Conversely, the fast filling regime occurs when the filling-to-suction velocity ratio exceeds the critical ratio, implying that the filling phase is faster than the suction phase. This study reveals, for the first time, that when the powder flow pattern during suction filling is dominated by plug flow, full die fill (i.e., the fill ratio equals unity) is achieved in the slow filling regime. However, in the fast filling regime, incomplete die fill is obtained. It is also found that when plug flow prevails during fast filling, the fill ratio has an inverse correlation with the filling-to-suction velocity ratio. This study further reveals that when the plug flow assumption is valid, the filling ratio at various fill-to-suction velocity ratios can be well predicted mathematically. Furthermore, it is also found that once the powder flow pattern differs from the ideal plug flow, which could be induced by the filling conditions and powder cohesion, the fill ratio can be overpredicted.

Dataset of the temperature rise during granular flows in a rotating drum.

This paper provides experimental data on the temperature rise during granular flows in a small-scale rotating drum due to heat generation. All heat is believed to be generated by conversion of some mechanical energy, through mechanisms such as friction and collisions between particles and between particles and walls. Particles of different material types were used, while multiple rotation speeds were considered, and the drum was filled with different amounts of particles. The temperature of the granular materials inside the rotating drum was monitored using a thermal camera. The temperature increases at specific times of each experiment are presented in form of tables, along with the average and standard deviation of the repetitions of each setup configuration. The data can be used as a reference to set the operating conditions of rotating drums, in addition to calibrating numerical models and validating computer simulations.

Numerical analysis of die filling with a forced feeder using GPU-enhanced discrete element methods.

Understanding die filling behaviour of powders is critical in developing optimal formulation and processes in various industries, such as pharmaceuticals and fine chemicals. In this paper, forced die filling is analysed using a graphics processing unit (GPU) based discrete element method (DEM), for which a powder feeder equipped with a wired stirrer is considered. The influences of operating parameters, such as the initial powder bed height, the filling speed, and the stirrer speed, on the die filling performance are systematically explored. It is shown that a larger initial powder bed height leads to a higher filling ratio, which can be attributed to a higher filling intensity; while the deposited particle mass in the die is almost independent of the powder bed height, when the initial fill level is larger than a critical bed height. Additionally, the filling ratio slightly increases with the increase of stirrer speed for cases with a stirrer, while the filling ratios are lower than that without a stirrer, which is attributed to the stirrer occupying some space above the die and reducing the effective discharge area. The obtained results can provide useful information for optimising the feeder system design and the operating condition.

Impact breakage of single pharmaceutical tablets in an air gun.

Milling is commonly used for controlling the size distribution of granules in the pharmaceutical dry granulation process. A thorough understanding of the breakage of single compacts is crucial in unravelling the complex interactions that exist between different pharmaceutical feed materials and the mill process conditions. However, limited studies in the literature have examined the impact breakage of single pharmaceutical compacts. In this study, pharmaceutical powders including the microcrystalline MCC 101, MCC 102 and MCC DG were compressed at different pressures and tablets with different porosities and thicknesses were produced. Impact breakage tests were conducted in an air gun and the tablet impact velocities and breakage patterns were analysed using a Phantom ultrahigh-speed camera. It was observed that the tablet breakage rate and the amount of fines reduced as the tablet porosity decreased. In addition, thin tablets with low porosity exhibited semi-brittle fracture and less intense crack propagation while thick tablets with high porosity primarily disintegrated into fine fragments. Thus, this study provides a better understanding of the breakage behaviour of different pharmaceutical materials and can potentially be used to describe the breakage modes of compacts in the ribbon milling processes.

Powder flow during linear and rotary die filling.

In the pharmaceutical industry, linear die filling is widely employed in R&D, while rotary die filling is very common in commercial production. It is not clear if powder die filling behaviour in a linear die filling system is representative of the flow performance in a rotary tablet press. In this study, a linear die filling system and a rotary die filling system were used to examine flow behaviours of both poor-flowing and free-flowing powders. It was found that the performance of poor-flowing powder in the linear die filling system is slightly better than that in the rotary die filling system, while the performance of free-flowing powders in the linear die filling system is similar to that in the rotary die filling system. Hence, it is suitable to use the linear die filling system to estimate the flow behaviour during rotary die filling with free-flowing powders, but caution needs to be taken when poor-flowing powders are used.

The effects of screw-to-roll speed ratio on ribbon porosity during roll compaction.

Dry granulation through roll compaction is a technology commonly used in the pharmaceutical industry for producing roll compacted ribbons. The significance of the feed screw speed and roll speed during ribbon production was highlighted in recent publications. However, previous studies focused primarily on the individual effects of either the feed screw speed or roll speed on ribbon porosity, and the synergetic effect of these parameters was rarely examined. The aim of this study therefore was to investigate the effects of the screw-to-roll speed ratio on the porosity of roll compacted ribbons, produced at different roll compaction conditions using the microcrystalline cellulose MCC, Avicel PH-102 feed material. It was observed that ribbon porosity decreased linearly with increasing screw-to-roll speed ratio. Furthermore, an increase in the speed ratio led to an increase in the roll gap and mass throughput while a decrease in the screw constant was observed. Thus, this study demonstrates that the screw-to-roll speed ratio can be treated as one of the critical process parameters for controlling ribbon porosity and can also be used to determine the optimum operating regimes during roll compaction.

Impact of feed material properties on the milling of pharmaceutical ribbons: A PBM analysis.

Dry granulation is commonly used in the pharmaceutical industry for compressing heat and moisture sensitive feed materials into compacts, subsequently followed by milling. Population balance models (PBMs) are often used to explore the effects of milling conditions on the granule size distribution (GSD) but limited studies have investigated the effects of the feed material and ribbon properties on the resulting GSD. In this work, a variety of feed materials and ribbons with different mechanical properties were used to validate a mass-based bi-modal breakage function developed in a previous study (Olaleye et al., 2019). Ribbon like tablets (referred to as ribblets) with a range of precisely controlled porosities were produced using an Instron machine and pharmaceutical excipients including the microcrystalline cellulose MCC 101, MCC DG and a DCPA/MCC mixture. Roll compacted ribbons were also produced using MCC 102 and MCC DG excipients. The ribblets and ribbons were milled in an impact-dominated cutting mill and PBM parameters were obtained from the ribblet milling data. Mechanistic models related to the feed ribbon property were then developed. It was found that the PBM with the mass-based bi-modal breakage function can accurately predict the GSDs of both the milled ribblets and roll compacted ribbons. The model developed was successfully linked to ribbon properties such as porosity for the first time and the model parameter a that reflects the fines mode in the bi-modal breakage function increased linearly with ribblet porosity. This work demonstrates the versatility of the developed PBM and provides a systematic approach for describing the ribbon milling process.

Data on rotary die filling performance of various pharmaceutical powders.

As one of critical process steps during pharmaceutical tabletting, rotary die filling is still not well understood. To address this issue, a model rotary die filling system with a paddle feeder was developed to closely mimic the industrial process. Using this model system, the performance of various pharmaceutical powders at different turret and paddle speeds was evaluated, and the dependence of fill variation on process conditions and material properties was examined. A comprehensive dataset was created and reported here to show the effects of material and process parameters on the die filling performance and the filling consistency. It is believed that the data can also be used for data-driven process modelling and for developing robust machine learning models for pharmaceutical manufacturing.