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To facilitate in vivo animal experiments exploring high-frequency nanosecond pulsed magnetic field therapy for tumor treatment, a specialized high-frequency nanosecond pulsed magnetic field generator has been developed. This generator is crafted for ablative subcutaneous tumors in vivo, and its waveform is adjustable, enabling the generation of triangular, trapezoidal, and step-like pulsed magnetic fields. In response to the semi-convex ellipsoidal structure of surface tumors, this article introduces a novel low-inductance stacked spiral coil. Utilizing a genetic algorithm, optimal structural parameters are determined to enable the coil to generate higher magnetic induction intensity in the tumor region under a specified output capacity of the current generator. Subsequently, a six-stage linear transformer driver (LTD)-type nanosecond pulsed current generator with a continuous flow circuit for inductive loads is developed, capable of stably outputting a pulsed current of 800 A. In conclusion, the test results confirm the pulsed current generator’s ability to consistently produce a pulsed current with a repetition frequency of 10 kHz, a pulsewidth of 800 ns, and an amplitude of 800 A on a $2.6~\mu \text{H}$ inductive load. As a result, it can generate triangular, trapezoidal, and step-shaped pulsed magnetic field in the ellipsoidal surface tumor area with a diameter of $10\times 8\times8$ mm. These fields exhibit a width of 800 ns, a maximum operating repetition frequency of 10 kHz, and an average magnetic induction intensity of 0.75 T. This lays the groundwork for the subsequent implementation of animal experiments.

Pulsed magnetic field treatment can enhance cell membrane permeability, allowing large molecular substances that normally cannot pass through the cell membrane to enter the cell. This research holds significant prospects for biomedical applications. However, the mechanism underlying pulsed magnetic field-induced cell permeabilization remains unclear, impeding further progress in research related to pulsed magnetic field. Currently, hypotheses about the mechanism are struggling to explain experimental results. Therefore, this study developed a parameter-adjustable pulsed magnetic field generator and designed experiments. Starting from the widely accepted hypothesis of “induced electric fields by pulsed magnetic field,” we conducted a preliminary exploration of the biophysical mechanisms underlying pulsed magnetic field-induced cell permeabilization. Finally, we have arrived at an intriguing conclusion: under the current technical parameters, the impact of the pulsed magnetic field itself is the primary factor influencing changes in cell membrane permeability, rather than the induced electric field. This conclusion holds significant implications for understanding the biophysical mechanisms behind pulsed magnetic field therapy and its potential biomedical applications.

The noncontact pulsed magnetic field (PMF) treatment can enhance cell membrane permeability, but its efficiency is relatively low. To enhance its efficiency, this article has developed a more optimized PMF generator: this generator can produce a maximum magnetic induction intensity of 1.9 T; and a maximum-induced electric field of approximately 110 V/cm with a uniformity of up to 84%. Importantly, the generator developed in this article can also generate a higher spatial gradient of the magnetic field, approximately 1000 T/m, a capability that was previously lacking in research. Subsequently, by customizing the coil structure and the heat dissipation system, we ensured both temperature control of the treatment plane and a sufficiently large effective treatment volume. Finally, the effectiveness of the PMF generator was confirmed through in vitro cell experiments.

Film capacitors are used as the key energy storage device for high-power pulse generators, and partial discharge (PD) is an important factor leading to insulation degradation and the failure of film capacitors. To accurately evaluate the effect of the rise rate on PD under nanosecond pulse voltage, experiments on the PD characteristics of biaxially oriented polypropylene (BOPP) films under high rise rate (18.3–140 V/ns) nanosecond pulse voltages were carried out. The PDs were mostly concentrated in the rising and falling phases of the nanosecond pulse. Moreover, the repetitive PD inception voltage (RPDIV) first increased and then remained unchanged as the rise time increased, and the PD amplitude and the number of discharges in the rising phase of the nanosecond pulse increased as the rise rate increased, while the discharge time lag decreased gradually. The PD amplitude, the number of discharges, and the discharge time lag in the falling phase of the nanosecond pulse all increased as the rise rate increased. In addition, when the rise rate was less than 50 V/ns, the PD statistical characteristics changed rapidly as the rise rate increased, and when the rise rate was greater than 50 V/ns, the PD statistical characteristics gradually changed more slowly as the rise rate increased.

A Cd(II)-based coordination polymer {[Cd2(5-F-1,3-bpeb)2(FBA)4]·H2O}n(CP1) was obtained from Cd(II) salt, 5-fluoro-1,3-bis[2-(4-pyridyl)ethenyl]benzene (5-F-1,3-bpeb), and p-fluorobenzoic acid (HFBA). Within the one-dimensional chain structure of CP1, a pair of 5-F-1,3-bpeb was arranged in a face-to-face style. Upon UV irradiation and heat treatment, multiple cyclobutane isomers, including specific monocyclobutanes (1with an endo-cyclobutane ring in CP1-1and 1′with an exo-cyclobutane ring in CP1-1′) and dicyclobutanes (endo,endo-dicyclobutane 2αin CP1-2α, exo,endo-dicyclobutane 2βin CP1-2β, and exo,exo-dicyclobutane 2γin CP1-2γ) were stereoselectively produced. These isomers could be interconverted inside the CPvia cutting/coupling specific bonds, which may be regarded as a type of molecular surgery. The precision of cutting/coupling relied on the thermal stability of the cyclobutanes and the alignment of the reactive alkene centers. The conversion processes were tracked through nuclear magnetic resonance, in situ powder X-ray diffraction, and IR spectroscopy. This approach can be considered as skeletal editing to construct complex organic compounds directly from one precursor.

Application of nanosecond pulsed electric fields to insulating nanoparticles can be used to prepare oriented high-performance composites, but the mechanism and related laws are still unclear. Therefore, in this article, highly insulating boron nitride nanosheet (BNNS) nanoparticles are selected, their alignment motions under different nanosecond intraburst frequencies (100 Hz–1 MHz) are studied for the first time in both experiments and simulations, and the two sets of results are compared and analyzed. The results show that the simulation results based on COMSOL are in good agreement with the experimental results, the variations in the local orientation angle with time and the local orientation time with intraburst frequency can be expressed by an allometric function, and the variation in the center-to-center distance with time can be described by an exponential decay function. Further experiments show that with the continuous application of the pulsed electric field, short chains of BNNSs continue to move to form longer chains, and long chains of $342~\mu \text{m}$ form under the external application of the pulsed electric field for 3 min. The good agreement between experiments and simulations verifies the strong reliability of the proposed theory and the established mathematical model for predicting the orientation alignment motion of BNNS particles. The theory and simulation method can be used as effective tools to predict the trajectories of nanoparticles under a nanosecond pulsed electric field and their final alignment into chains.

As a non-heat input solid-state joining technology, electromagnetic pulse welding (EMPW) has many advantages in the connection of dissimilar metals. Finite element (FE) methods are often used to design the EMPW equipment, explore the parameters and analyze the transient process. However, it is difficult to reflect the welding effect directly. This work proposed a welding effect evaluation model based on the welding window theory and the Vc-βtrajectory curve obtained in the FE simulation. A FE model coupling the circuit-magnetic-structure field was established in COMSOL software to simulate the EMPW process of the Cu plate and Al plate. The Vc-βtrajectory curve and welding traces were obtained according to the simulation results. An experimental platform WD-28 was used to carry out the welding experiments of Cu–Al plates at different discharging voltages. The welding traces were measured through SEM method and compared with the simulation results. According to the comparative result, the empirical constant of the calculation formula for the lower boundary of the welding window was adjusted into 1.6, so that the evaluation result was consistent with the experimental result. This work can provide a new method for evaluating directly the welding effect through the FE simulation results.

Progress has been achieved in many fields in understanding the biological mechanisms of depression, including genome-wide association analysis, neurotransmitter system function, brain regions and neural networks, inflammatory response, neuroplasticity, neuroimaging, and neuro electrophysiology. These progresses provide a reliable basis for developing the medical and physical therapies for depression. However, the current treatments developed from biological mechanisms can only address less than 60 % of depressive symptoms and have limited efficacy in improving social functioning and reducing recurrence. Studies have explored the non-biological mechanisms of depression in mental fields. These progresses are helpful to develop more interventions that could alleviate depressive symptoms, improve functional impairments, and reduce recurrence, thereby promoting a more comprehensive recovery in depressed patients. However, there is not a systematic and deep review to highlight the non-biological mechanisms of depression.

Intelligent reflecting surface (IRS) is a revolutionary technology for achieving spectral- and energy-efficient wireless networks. By adjusting the phase shifts at the IRS, a high passive beamforming gain can be achieved, which is particularly appealing for improving the spectral efficiency of wireless powered communication networks (WPCNs). Inspired by this, we study IRS-aided WPCNs, where the IRS is leveraged to help the energy transmitter (ET) broadcast the energy signals to the distributed devices in the downlink (DL), and meanwhile help the distributed devices forward the information signals to the information receiver (IR) in the uplink (UL). By taking account into the system energy consumption and achievable system throughput, we aim to maximize the energy efficiency (EE) of WPCNs by jointly optimizing phase shifts at the IRS, the beamformer at the ET, time allocation, and the transmit power of devices while guaranteeing the minimum achievable rate requirements for the devices. Since the formulated optimization problem is a nonlinear fractional programming problem, which is non-convex. To tackle this difficulty, an alternating optimization (AO) algorithm is proposed. In particular, a Dinkelbach-based algorithm is proposed to optimize the resource allocation, and a penalty-based algorithm based on the difference of convex (DC) programming and successive convex approximation (SCA) techniques is proposed to solve the phase shift optimization. Simulation results unveil that the IRS is capable of improving the system EE compared to the benchmarks.

Neurodegenerative diseases place a heavy burden on patients, their families, society, and health care systems. The polyphenols in the diet have inherent antioxidant and anti-inflammatory properties that can inhibit oxidative stress and modulate certain neurotransmitters to improve symptoms of neurodegenerative diseases. However, due to the low bioavailability of polyphenols and the difficulty of crossing the blood-brain barrier on their own, it is necessary to use suitable delivery carriers. In this review, we provided an overview of the pathogenesis of neurodegenerative diseases and introduced the therapeutic effects of polyphenols for neurodegenerative diseases. Crucially, we have described a biomimetic strategy, and presented the potential and advantages of the application of different cell membranes in wrapping cargoes, as well as the potential shortcomings that exist. The delivery strategy based on biomimetic cell membrane vesicles improves the application potential of dietary polyphenols in neurodegenerative diseases.

Ameliorating microglia-mediated neuroinflammation is a crucial strategy in developing new drugs for neurodegenerative diseases. Plant compounds are an important screening target for the discovery of drugs for the treatment of neurodegenerative diseases. However, due to the spatial complexity of phytochemicals, it becomes particularly important to evaluate the effectiveness of compounds while avoiding the mixing of cytotoxic substances in the early stages of compound screening. Traditional high-throughput screening methods suffer from high cost and low efficiency. A computational model based on machine learning provides a novel avenue for cytotoxicity determination. In this study, a microglia cytotoxicity classifier was developed using a machine learning approach. First, we proposed a data splitting strategy based on the molecule murcko generic scaffold, under this condition, three machine learning approaches were coupled with three kinds of molecular representation methods to construct microglia cytotoxicity classifier, which were then compared and assessed by the predictive accuracy, balanced accuracy, F1-score, and Matthews Correlation Coefficient. Then, the recursive feature elimination integrated with support vector machine (RFE-SVC) dimension reduction method was introduced to molecular fingerprints with high dimensions to further improve the model performance. Among all the microglial cytotoxicity classifiers, the SVM coupled with ECFP4 fingerprint after feature selection (ECFP4-RFE-SVM) obtained the most accurate classification for the test set (ACC of 0.99, BA of 0.99, F1-score of 0.99, MCC of 0.97). Finally, the Shapley additive explanations (SHAP) method was used in interpreting the microglia cytotoxicity classifier and key substructure smart identified as structural alerts. Experimental results show that ECFP4-RFE-SVM have reliable classification capability for microglia cytotoxicity, and SHAP can not only provide a rational explanation for microglia cytotoxicity predictions, but also offer a guideline for subsequent molecular cytotoxicity modifications.

Objective Cerebral infarction has a poor prognosis and causes a serious burden on families and society. Recombinant tissue plasminogen activator (rt-PA) and urokinase (UK) are commonly used thrombolytic agents in the clinic. However, direct and powerful clinical trial evidence to determine the therapeutic effect of rt-PA and UK on intravenous thrombolysis is lacking.Methods In this study, 180 patients with acute cerebral infarction were treated with rt-PA or UK. The National Institutes of Health Stroke Scale (NIHSS) scores, Barthel index, bleeding complications, and biomarkers were evaluated.Results No significant differences in NIHSS or Barthel scores were found between the groups. However, UK increased the risk of intracranial haemorrhage compared with rt-PA. rt-PA had increased activity in reducing serum levels of MMP-9 than UK.Conclusion Intravenous thrombolysis with rt-PA and UK in the time window of acute cerebral infarction can achieve similar therapeutic effects, but rt-PA can further reduce the risk of cerebral haemorrhage and is relatively safer than UK.

Unprecedented interheteromacrocyclic hosts charge transfer (CT) crystals were generated by cooling organic solutions containing p-dimethoxybenzene-constituted pillar[5]arene (P5A) and p-benzoquinone-constituted pillar[5]quinone (P5Q). Despite the weak CT interaction known between p-dimethoxybenzene and p-benzoquinone and the lack of formation of CT complexes between P5Aand P5Qin the solution phase, CT cocrystals between P5Aand P5Qwere formed with solvent molecules included into the hosts’ cavities. Such a cocrystallization arises from an elegant synergy between the CT interaction and solvent-binding-promoted crystallization. The interhetero hosts CT crystals were studied by optical and electron microscopic techniques, X-ray powder diffraction, solid-state NMR, UV–vis, IR spectroscopic studies, and X-ray single-crystal studies. The solvent complexation was critical for formation of the supramolecular CT microcrystals. The CT absorption bands faded upon removing the solvent molecules under vacuum, but they could be recovered by reuptake of the solvent molecules. Intriguingly, the CT absorption bands and uptake kinetics are distinguishably different for various organic solvents, thus providing a unique way to distinguish between different commonly used chemicals.

A multihydroquinone ether dialdehyde derivative 2was incidentally obtained through an unexpected ring opening of pillar[4]arene[1]quinone 1. And the Prato reaction of 2with [60]fullerene led to [60]fullerene bisadducts, from which trans-4cyclic regioisomer 3was isolated and characterized. The fulleropillar[4]arene 3showed a larger cavity and can accommodate a viologen derivative C12V2+with a much stronger affinity than permethyl pillar[5]arene (MP5) and pillar[4]arene[1]quinone 1.

To obtain a pure product without the isomer byproducts is a goal that many chemists are pursuing. As one kind of very important synthesis method, the photochemical reaction is simple and straightforward yet low-selective. In this work, a coordination interaction-based oriented synthesis strategy has been proposed to realize the precise stereochemical control of the isomeric cyclic compounds in the photocycloaddition reaction. Through fixing the reactants via coordination interactions, the arrangements and configurations of the reactants can be adjusted, thereby successfully producing all of the related photocycloaddition products without isomer byproducts for the first time. This work not only provides a new route to synthesize the pure cyclic compounds but also expands the application of the photocycloaddition reaction.

An efficient protocol for C–C coupling has been developed using three iodo-bridged copper(I) complexes as catalysts. Complexes [CuI(bpy)]2(1), [CuI(phen)]2·DMF (2), and [CuI(Mephen)]2(3) were successfully synthesized via solvothermal method (bpy = 2,2′-dipyridyl, phen = 1,10-phenanthroline, and Mephen = 2,9-dimethylphenanthroline). The self-coupling reaction of phenylboronic acid was selected as a model reaction to evaluate the catalytic property of the complexes. Moreover, this method tolerates various substituents on the arylboronic acids such as halogens, carbonyls, and nitro groups. It shows that the iodo-bridged Cu(I) center serves as the active site to activate molecular oxygen during the catalytic process. The result illustrates that these complexes were found to be excellent catalysts for self-coupling of arylboronic acids under mild conditions.

A convenient photoelectrochemical sensor was constructed based on the synergistic contributions of an ultrathin BiOCl nanosheet and anchored TiO2nanoparticles to detect the organophosphorus pesticide chlorpyrifos. As expected, the fabricated heterostructure showed a distinct improvement in photocurrent intensity compared with pristine BiOCl and TiO2. This remarkable enhancement may be attributed to the separation and transfer of photogenerated charge carries, which benefit from intimate interfacial interactions between the ultrathin BiOCl nanosheets and TiO2nanoparticles. Based on the robust photocurrent signal, a novel PEC sensor was established for the sensitive and selective detection of chlorpyrifos. The as-fabricated PEC sensor demonstrates many advantages such as a wide linear range of 1–12 μM, a low detection limit of 0.11 μM, S/N = 3, and remarkable convenience, which provides a general format for chlorpyrifos detection in green vegetable analysis.

Eucalyptusdimers A–C, three dimeric phellandrene-derived meroterpenoids featuring an unprecedented, fused skeleton between two phellandrene and two acylphloroglucinol subunits, along with one biogenetically related intermediate, (±)-eucalyprobusone A, were isolated from the fruits of Eucalyptus robusta. Their structures and absolute configurations were elucidated using spectroscopic data, X-ray crystallography, and electronic circular dichroism analysis. The isolated meroterpenoids were evaluated for their anti-inflammatory, acetylcholinesterase inhibitory, and protein tyrosine phosphatase 1B inhibitory effects.

Janus heteronanostructures (HNs), as an important class of anisotropic nanomaterials, could facilitate synergistic coupling of diverse functions inherited by their comprised nanocomponents. Nowadays, synthesizing deterministically targeted Janus HNs remains a challenge. Here, a general yet scalable technique is utilized to fabricate an array of programmable Janus HNs based on anodic aluminum oxide binary-pore templates. By designing and employing an overetching process to partially expose four-edges of one set of nanocomponents in a binary-pore template, selective deposition and interfacing of the other set of nanocomponents is successfully achieved along the exposed four-edges to form a densely packed array of Janus HNs on a large scale. In combination with an upgraded two-step anodization, the synthesis provides high degrees of freedom for both nanocomponents of the Janus HNs, including morphologies, compositions, dimensions, and interfacial junctions. Arrays of TiO2–Au and TiO2/Pt NPs–Au Janus HNs are designed, fabricated, and demonstrated about 2.2 times photocurrent density and 4.6 times H2evolution rate of that obtained from their TiO2counterparts. The enhancement was mainly determined as a result of localized surface plasmon resonance induced direct hot electron injection and strong plasmon resonance energy transfer near the interfaces of TiO2nanotubes and Au nanorods. This study may represent a promising step forward to pursue customized Janus HNs, leading to novel physicochemical effects and device applications.

Aluminium oxide was deposited on silicon, silicon carbide and epitaxial graphene grown on silicon carbide by atomic layer deposition using a standard MOCVD equipment. The morphology and the electrical properties of the aluminium oxide layers on both substrates were determined and compared to aluminium oxide layers deposited with a standard atomic layer deposition equipment. The high-k material fabricated with the developed MOCVD process show comparable or better properties compared to the standard atomic layer deposition process.

•The MOFs were exfoliated into single- or double-layer nanosheets.•The nanosheet of MOFs expose a large number of active sites for detection of FA.•MOFs nanosheets can be used as fluorescent test paper to visual detection of FA.

Plasmonic nanostructures have been widely incorporated into different semiconductor materials to improve solar energy conversion. An important point is how to manipulate the incident light so that more light can be efficiently scattered and absorbed within the semiconductors. Here, by using a tunable three-dimensional Au pillar/truncated-pyramid (PTP) array as a plasmonic coupler, a superior optical absorption of about 95% within a wide wavelength range is demonstrated from an assembled CdS/Au PTP photoanode. Based on incident photon to current efficiency measurements and the corresponding finite difference time domain simulations, it is concluded that the enhancement is mainly attributed to an appropriate spectral complementation between surface plasmon resonance modes and photonic modes in the Au PTP structure over the operational spectrum. Because both of them are wavelength-dependent, the Au PTP profile and CdS thickness are further adjusted to take full advantage of the complementary effect, and subsequently, an angle-independent photocurrent with an enhancement of about 400% was obtained. The designed plasmonic PTP nanostructure of Au is highly robust, and it could be easily extended to other plasmonic metals equipped with semiconductor thin films for photovoltaic and photoelectrochemical cells.

Several physico-chemical effects and properties in the solid state involve nanoscale interactions between adjacent materials and morphologies. Arrays of binary nanostructures can generate intimate interactions between different sub-components, but fabricating binary nanostructures is challenging. Here, we propose a concept to achieve diverse binary nanostructure arrays with high degrees of controllability for each of the sub-components, including material, dimension and morphology. This binary nanostructuring concept originates with a distinctive binary-pore anodized aluminium oxide template that includes two dissimilar sets of pores in one matrix, where the openings of the two sets of pores are towards opposite sides of the template. Using the same growth mechanism, the binary-pore template can be extended to multi-pore templates with more geometrical options. We also present photoelectrodes, transistors and plasmonic devices made with our binary nanostructure arrays using different combination of materials and morphologies, and demonstrate superior performances compared to their single-component counterparts.

Maximizing solar energy utilization is a persistent challenge in photocatalysis, which determines sustainable solar-driven photocatalytic process. Photothermal-coupled photocatalysis is considered as a promising solution to tackle the issues of sustainable energy scarcity and environmental pollution by harvesting the full-spectrum solar energy. Herein, a highly efficient photothermal-accelerated photocatalysis system is elaborately established, in which the assembled carbonized stick/Nb2C MXene evaporator can heat water into vapor and the integrated g-C3N4photocatalyst further enables high-efficiency photocatalytic hydrogen production. The designed hyperboloid wood-based architecture possesses a multiphase interface of water steam/ catalyst/ hydrogen to reduce the transport resistance of hydrogen gas in liquid and ultimately maximize the output of hydrogen energy. Consequently, this coupled photothermal-photocatalytic system achieves a stable solar evaporation rate of 2.16 kg m-1h-1under one sun irradiation and highly efficient hydrogen-evolving rate of 3096 μmol g-1h-1. This work paves a way to explore the improvement of photocatalytic hydrogen production by synergic photothermal effect for potential applications in renewable solar energy utilization and hydrogen production.

To pursue high photocatalytic activity in visible-light region, the Fe(III) modified BiOCl ultrathin nanosheet (Fe(III)@BOC NS) has been firstly synthesized via a facile solvothermal approach. The morphological and compositional characterizations reveal that the thickness of the as-prepared Fe(III)@BOC NS is less than 5 atomic layer with the exposure of active [001] facets. And the Fe(III) doping and surface grafting result in a 0.58eV down-shift of the BiOCl conduction band minimum extending the light absorption from ultraviolet light to visible light region, as well as a promoted interfacial charge transfer upon visible light irradiation. Meanwhile, the Fe(III) modification introduces unique active sites on the surface of ultrathin nanosheet facilitating the surface reaction. Moreover, both of the appropriate self-induced electric field of [001] facets, and the shortened charge carrier diffusion length of ultrathin nanosheet enhance the separation and transfer efficiency of charge carriers. Therefore, by taking those advantages, we experimentally demonstrate that the Fe(III)@BOC NS is a high-efficiency visible-light photocatalyst for both of environment remediation and water splitting.

Background: Helicobacter pylori(H. pylori) eradication plays a crucial role in gastric cancer prevention, but the antimicrobial resistance of H. pyloriis obstructing this elimination process. In this study, we developed nanoclusters (NCs) from Zn0.3Fe2.7O4nanoparticles using a poly(ethylene glycol)-b-poly(ε-caprolactone)-based nanocarrier as an innovative antibiotic-independent H. pylorimanagement. Results: The nanocluster showed minimal toxicity and maximal biocompatibility. With a low concentration (50 µg/mL) of NCs under a short time period (~ 2 min) of near-infrared (808 nm) irradiation, we kept the culture medium temperature to 41 °C for 20 min with continuous irradiation. The heated NCs exhibited efficient photothermal effects and resulted in an excellent inhibition of H. pylorigrowth, adhesion and ability to induce vacuolization in eukaryotic cells in in vitro investigation. Transmission electron microscopy showed a dramatic morphologic change after NCs photothermia on H. pylori, including cell wall and membrane rupture, as well as ribosome damage. Besides, levofloxacin and clarithromycin resistance was decreased after photothermal treatment in H. pyloriNCTC 11637 and/or clinical strains, however metronidazole resistance was unchanged. We also discovered a significant decrease in the biofilm formation of H. pyloriunder the NCs-based photothermal application, while efflux pump function was unchanged. Conclusions: Based on this novel NCs-based photothermal approach, we were able to demonstrate in vitro a significant inhibition of both H. pylorigrowth and molecular toxicity, and its improvement in antibiotic sensitivity alone with the eradication of H. pyloribiofilms previously believed to be tolerant to conventional antibiotics.