Side Chain Programming Synchronously Enhances the Photothermal Conversion Efficiency and Photodynamic Activity of A-D-A Photosensitizers.

Synchronously improving the photothermal conversion efficiency and photodynamic activity of organic small molecule photosensitizers is crucial for their further wide application in cancer treatment. Recently, the emerging A-D-A photosensitizer-based phototherapy systems have attracted great interest due to their plentiful inherent merits. Herein, we propose a design strategy for A-D-A photosensitizers with synchronously enhanced photothermal conversion and reactive oxygen species (ROS) generation efficiencies. Side chain programming is carried out to design three A-D-A photosensitizers (IDT-H, IDT-Br, IDT-I) containing hexyl, bromohexyl, and iodohexyl side chains, respectively. Theoretical calculations confirm that a bulky iodine atom could weaken the intermolecular π-π stacking and enhance spin-orbit coupling constants of IDT-I. These molecular mechanisms enable IDT-I nanoparticles (NPs) to exhibit 2.4-fold and 1.7-fold higher ROS generation efficiency than that of IDT-H NPs and IDT-Br NPs, respectively, as well as the highest photothermal conversion efficiency. Both the experimental results in vitro and in vivo verify that IDT-I NPs are perfectly qualified for the mission of photothermal and photodynamic synergistic therapy. Therefore, in this contribution, we provide a promising perspective for the design of A-D-A photosensitizers with simultaneously improved photothermal and photodynamic therapy ability.

Integrated microcavity electric field sensors using Pound-Drever-Hall detection.

Discerning weak electric fields has important implications for cosmology, quantum technology, and identifying power system failures. Photonic integration of electric field sensors is highly desired for practical considerations and offers opportunities to improve performance by enhancing microwave and lightwave interactions. Here, we demonstrate a high-Q microcavity electric field sensor (MEFS) by leveraging the silicon chip-based thin film lithium niobate photonic integrated circuits. Using the Pound-Drever-Hall detection scheme, our MEFS achieves a detection sensitivity of 5.2 µV/(m[Formula: see text]), which surpasses previous lithium niobate electro-optical electric field sensors by nearly two orders of magnitude, and is comparable to atom-based quantum sensing approaches. Furthermore, our MEFS has a bandwidth that can be up to three orders of magnitude broader than quantum sensing approaches and measures fast electric field amplitude and phase variations in real-time. The ultra-sensitive MEFSs represent a significant step towards building electric field sensing networks and broaden the application spectrum of integrated microcavities.

End Group Engineering for Constructing A-D-A Fused-Ring Photosensitizers with Balanced Phototheranostics Performance.

Phototheranostics continues to flourish in cancer treatment. Due to the competitive relationships between these photophysical processes of fluorescence emission, photothermal conversion, and photodynamic action, it is critical to balance them through subtle photosensitizer designs. Herein, it is provided a useful guideline for constructing A-D-A photosensitizers with superior phototheranostics performance. Various cyanoacetate group-modified end groups containing ester side chains of different length are designed to construct a series of A-D-A photosensitizers (F8CA1 ∼ F8CA4) to study the structure-property relationships. It is surprising to find that the photophysical properties of A-D-A photosensitizers can be precisely regulated by these tiny structural changes. The results reveal that the increase in the steric hindrance of ester side chains has positive impacts on their photothermal conversion capabilities, but adverse impacts on the fluorescence emission and photodynamic activities. Notably, these tiny structural changes lead to their different aggregation behavior. The molecule mechanisms are detailedly explained by theoretical calculations. Finally, F8CA2 nanoparticles with more balanced photophysical properties perform well in fluorescence imaging-guided photothermal and type I&II photodynamic synergistic cancer therapy, even under hypoxic conditions. Therefore, this work provides a novel practicable construction strategy for desired A-D-A photosensitizers.

Study on the factors of hydrogen sulfide production from lignite bacterial sulfate reduction based on response surface method.

Bacterial sulfate reduction (BSR) is one of the key factors leading to the anomalous accumulation of hydrogen sulphide in coal mines. Environmental factors such as temperature and pH play a crucial role in the metabolism and degradation of coal by sulfate-reducing bacteria (SRB). In this study, coal samples were selected from Shengli Coal Mine, and SRB strains were isolated and purified from mine water using a dilution spread-plate anaerobic cultivation method. Based on single-factor experiments and response surface methodology (RSM), the impact of temperature, pH, oxidation-reduction potential (ORP), chemical oxygen demand to sulfate ratio (COD/SO42-) on the generation of hydrogen sulphide during brown coal BSR was analyzed. The results showed that the anaerobic degradation of coal by SRB was inhibited by either too high or too low a temperature to produce hydrogen sulfide, and the greatest production of hydrogen sulfide occurred at a temperature of about 30 °C; The greatest production of hydrogen sulfide occurred at an initial ambient pH of 7.5; COD/SO42- ratio of around 2.0 is most conducive to hydrogen sulphide generation; the lower ORP value is more favorable for hydrogen sulfide generation. The optimal conditions obtained by RSM were: temperature of 30.37 °C, pH of 7.64 and COD/SO42- of 1.96. Under these conditions, the hydrogen sulfide concentration was 56.79 mg/L, the pH value was 8.40, the ORP value was -274 mV, and the SO42- utilization rate was 58.04%. The RSM results showed that temperature, ambient pH and COD/SO42- had a significant effect on hydrogen sulfide production, and the degree of effect was: ambient pH > temperature > COD/SO42-.

End Group Nonplanarization Enhances Phototherapy Efficacy of A-D-A Fused-Ring Photosensitizer for Tumor Phototherapy.

Enhancing the phototherapy efficacy of organic photosensitizers through molecular design is a fascinating but challenging task. Herein, we propose a simple design strategy to first realize the generation of superoxide anion radical (O2•-) by A-D-A fused-ring photosensitizers. Through replacing one cyano group of traditional end group with an ester group, we designed a novel nonplanar end group (A unit) to synthesize a novel A-D-A photosensitizer F8CA. In a comparison with its counterpart F8CN with the traditional end group, F8CA displays more loose packing and larger spin-orbit coupling constants. The F8CA nanoparticles showed higher photodynamic activities with the generation capability of singlet oxygen (1O2), hydroxyl radical (•OH), and O2•-, while F8CN nanoparticles could only generate 1O2 and •OH. In addition, F8CA nanoparticles still remain high photothermal conversion efficiency (61%). As a result, F8CA nanoparticles perform well in hypoxia-tolerant tumor phototherapy. This study brings an effective design thought for A-D-A photosensitizers.

A nanoplatform for mild-temperature photothermal and type I & II photodynamic therapy in the NIR-II biowindow.

In the current work, we synthesized an A-D-A smallmolecule photosensitizer, denoted as DPTTIC, and a dual PEG-functionalized pillararene, denoted as WP5-8C-2PEG, and used them to construct novel DPTTIC nanoparticles (NPs) displaying NIR II absorption. Under 980 nm-wavelength laser irradiation, DPTTIC NPs performed well in mild-temperature photothermal and type I & II photodynamic anti-tumor therapy.

A-DA'D-A fused-ring small molecule-based nanoparticles for combined photothermal and photodynamic therapy of cancer.

New nanoparticles (Y6 NPs) based on the A-DA'D-A fused-ring conjugated small molecule Y6 have been prepared for the combined photothermal and photodynamic therapy of cancer. Y6 NPs show excellent light absorption from 300 to 900 nm, a good photothermal conversion efficiency of 57% and reactive oxygen species generation capability. The high photothermal conversion ability and superior photodynamic activity of Y6 NPs endow them with great potential for cancer therapy.

Illuminating the efficiency of CO2 emissions in China's mining sector: evidence from meta-frontier Malmquist index models.

CO2 emission reduction has become a binding target in China's economic and social development. The mining industry is China's primary energy consumer and therefore has an important influence on China's CO2 emissions. Herein, we conduct a comprehensive analysis of data from the Chinese mining industry between 2004 and 2015. And we employ meta-frontier data envelopment analysis to analyse the CO2 emission efficiency of the Chinese mining industry and identify the driving factors that influence the observed dynamic changes in CO2 emission efficiency. The main practical conclusions of our research are as follows: (1) the CO2 emission efficiency of China's mining industry had grown continuously during the study period; (2) during the study period, the CO2 emission efficiency of China's mining industry did not change consistently with changes in different geographical regions; (3) the overall efficiency of management in China's mining sector was low; (4) the small and medium enterprises (SMEs) in China's mining sector played a significant role in the improvement of the CO2 emission efficiency. The empirical results provide constructive policy implications that should be considered by the policy makers for the more sustainable development of China's mining sector.

Pillar[5]arene-Based [2]Rotaxane: Synthesis, Characterization, and Application in a Coupling Reaction.

Mechanically interlocked molecules are a class of smart supramolecular species because of their interesting topological structure and application in various areas, such as biology and nanoscience. In this work, we used "multicomponent reaction" to fabricate a new [2]rotaxane based on pillar[5]arene from different small-sized molecules. The molecular structure of the obtained [2]rotaxane R was confirmed by 1H and 13C NMR, high-resolution electrospray ionization mass spectrometry, two-dimensional nuclear Overhauser effect spectroscopy, and density functional theory studies. Interestingly, the [2]rotaxane-based organometallic cross-linked catalyst (Pd@R) was easily constructed via the coordination between triazole groups and Pd(NO3)2. Pd@R proved to be a good catalyst for the Suzuki-Miyaura coupling reaction with excellent stability and repeatability.

"Claw hand with a unilateral onset" as a regional variant of Guillain-Barre' syndrome: A case report.

RATIONALE: Although distal nerves located at sites prone to compression are susceptible to autoimmune attack, Guillain-Barre' syndrome (GBS) with exclusive hand muscle involvement is rarely found in clinics. All reported patients presented with a special variant - finger extensor weakness, especially claw hand caused by predominant ulnar extensor involvement. Similar to typical GBS, these patients showed bilateral symmetric onset with rapid clinical progression. PATIENT CONCERNS: A 62-year-old man with GBS was admitted to our hospital with unilateral onset of claw hand. He showed relatively slow progression and did not develop bilateral symmetric claw hands until 6 weeks later. DIAGNOSES: Eventually the patient was diagnosed as having a regional variant of GBS by neuronal electrophysiology and cerebrospinal fluid examinations. INTERVENTIONS: This patient was treated with intravenous thrombolysis within 4.5 hours of onset. Eventually he was diagnosed as having a regional variant of GBS and was treated with gamma-globulin (400 mg/kg/d) for 5 consecutive days via intravenous infusion. OUTCOMES: The patient had a slow recovery with persistent mild finger extensor weakness. LESSONS: This patient presented with unilateral onset of claw hand, and the diagnosis of acute ischemic stroke could not be excluded because of a short time window; hence, he was treated with intravenous thrombolysis within 4.5 hours of onset. Eventually he was diagnosed as having a regional variant of GBS. It is important that GBS should also be considered in patients with unilateral hand weakness and unknown aetiology in the early stages of disease.

A Discrete Platinum(II) Amphiphile: Construction, Characterization, and Controllable Self-Assembly in Different Solvents.

"Coordination-driven self-assembly" offers us an efficient method to fabricate 3D metallacages and 2D metallacycles with controllable shape and size via simple building blocks. Herein, a new discrete platinum(II) amphiphile (AOM), which contains hydrophilic tris(ethylene oxide) chains and a hydrophobic porphyrin unit, was constructed successfully by using "coordination-driven self-assembly". From various characterization methods, such as UV-vis spectroscopy, dynamic light scattering, transmission electron microscopy, scanning electron microscopy, and small-angle X-ray scattering, we found that AOM can self-assemble into vesicles, curved vesicles with open ends, and at last stable bilayer nanotubes in aqueous solution at room temperature and flexible cross-linked structures at about 60 °C. In contrast, AOM formed rigid bilayer nanosheets of micrometers in width and millimeters in length in n-hexane. We hope this investigation will pave the way for the fabrication of controllable soft materials.

Respiratory electrophysiologic studies in chronic obstructive pulmonary disease.

Respiratory failure is common during acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). Phrenic nerve conduction (PNC), transcranial magnetic stimulation (TMS), and cervical magnetic stimulation (CMS) are of great value in identifying the feature and site of AE-COPD.PNC, TMS, and CMS were performed in 20 AE-COPD patients with respiratory failure, and re-examined after weaning. Latencies and amplitudes of the diaphragmatic compound muscle action potential (dCMAP), motor evoked potential of the diaphragm (dMEP) evoked by TMS and CMS, and central motor conduction time (CMCT) were measured. Blood gas analysis and serum electrolyte levels were also evaluated. The results were compared with those from 20 healthy subjects.AE-COPD patients showed prolonged CMCT and latencies of dCMAP and dMEP, decreased amplitudes of dCMAP and dMEP evoked by CMS, while CMCT and the latency of dMEP evoked by TMS were shortened after weaning. Significant correlation was identified between arterial blood gas analysis, serum electrolyte levels, disease duration, the duration of mechanical ventilation and the electrophysiological findings in AE-COPD patients prior to weaning.The central and peripheral respiratory pathway is involved in AE-COPD. Central respiratory pathway function is improved after weaning in AE-COPD patients with respiratory failure.

Impact of impaired glucose regulation on the functions of large and small fibers of peripheral nerves

Background/aim: This article analyzes the incidence and characteristics of peripheral neuropathy in patients with impaired glucose regulation (IGR). Materials and methods: A total of 120 IGR patients and 60 healthy controls were enrolled. All subjects underwent nerve conduction study (NCS) of large fibers and skin sympathetic response (SSR) and contact heat pain evoked potential (CHEP) testing of small fibers with a Medtronic Keypoint machine (Medoc Ltd., Israel). IGR patients were evaluated using the Michigan Neuropathy Screening Instrument (MNSI). Results: The abnormal rates (MNSI >2) in IGR patients and NCS and SSR evaluations were 18.3%, 22.5%, and 39.2%, respectively. All abnormal NCS findings were accompanied with abnormal SSR findings. Compared with the control group, the sensory nerve action potential wave of the posterior tibial and sural nerve was decreased in the IGR group (P = 0.01, P = 0.00), the SSR wave was reduced in the upper and lower limbs (P = 0.002, P = 0.00), and the CHEP wave was decreased in opisthenar and shank (P = 0.00). Compared with the control group, the CHEP wave was decreased in the shank in the normal SSR group (P < 0.05) and in the opisthenar and shank in the normal NCS group (P < 0.05). Conclusion: IGR patients have peripheral neuropathy characterized by impaired functions of large and small fibers focused on small fiber and lower limb sensory nerves. CHEP can detect small fiber damage earlier than SSR and NCS.

Plumbagin inhibits amyloid-ß-induced neurotoxicity: regulation of oxidative stress and nuclear factor erythroid 2-related factor 2 activation.

ß-Amyloid (Aß) species probably exert neurotoxic effects in Alzheimer's disease. In the present study, the effect of antioxidant plumbagin was tested against Aß25-35-induced neurotoxicity in the SH-SY5Y cell line. Cell viability was determined using an MTT assay. Antioxidant status was analyzed through antioxidant enzyme activities, nuclear factor erythroid 2-related factor 2 (Nrf-2), and its downstream protein expressions. Inflammatory response was determined through nuclear factor-κB (NF-κB) pathway and cytokine expressions. Aß25-35 showed a decrease in cell viability in a concentration-dependent manner. The IC50 value was found to be 17 µM. Pretreatment with plumbagin prevented Aß25-35-induced toxicity by improving the cell viability up to 96%. Plumbagin inhibited Aß25-35-induced oxidative stress by decreasing reactive oxygen species and lipid peroxidation. Aß25-35-induced redox imbalance caused decreased Nrf-2 expression, with downregulation Nrf-2 target proteins heme oxygenase 1 and NAD(P)H dehydrogenase (quinone 1) during Aß25-35 treatment. However, plumbagin improved the antioxidant defense system by increasing Nrf-2 expression with concomitant upregulation in heme oxygenase 1 and NAD(P)H dehydrogenase (quinone 1). Aß25-35 induced inflammatory response through upregulated NF-κB, cyclooxygenase-2, and inducible nitric oxide synthase levels. Plumbagin exerted anti-inflammatory effects by decreasing NF-κB, cyclooxygenase-2, and inducible nitric oxide synthase levels. Aß25-35-induced increases in proinflammatory cytokine (interleukin-8, interleukin-6, and monocyte chemoattractant protein-1) expressions were suppressed by plumbagin pretreatment. Altogether, the present study indicates that plumbagin prevents redox status and inflammatory activation during Aß25-35-induced toxicity by modulating the antioxidant defense system and Nrf-2 signaling.

Organ- and cell-specific immune responses are associated with the outcomes of intracerebral hemorrhage.

Severe brain injury significantly influences immune responses; however, the levels at which this influence occurs and which neurogenic pathways are involved are not well defined. Here, we used MRI to measure spleen volume and tissue diffusion changes in patients with intracerebral hemorrhage (ICH). We observed increased capillary exchange and spleen shrinkage by d 3 post-ICH, with recovery by d 14. The extent of spleen shrinkage was associated with brain hematoma size, and a reduced progression of perihematomal edema was observed in the presence of severe spleen shrinkage. At the cellular level, lymphopenia was present in patients with ICH at admission and persisted up to 14 d. Lymphopenia did not parallel the observed spleen alteration. In addition, patients with ICH with infection had significant deficiencies of T and NK cells and poor functional outcomes. Finally, in mouse models of ICH, spleen shrinkage could be related to innervations from adrenergic input and the hypothalamus-pituitary-adrenal (HPA) axis. In sum, the profound impact of ICH on the immune system involves the coordinated actions of sympathetic innervation and the HPA axis, which modulate spleen shrinkage and cellular immunity.-Zhang, J., Shi, K., Li, Z., Li, M., Han, Y., Wang, L., Zhang, Z., Yu, C., Zhang, F., Song, L., Dong, J.-F., La Cava, A., Sheth, K. N., Shi, F.-D. Organ- and cell-specific immune responses are associated with the outcomes of intracerebral hemorrhage.

Inhibition of miR-143 during ischemia cerebral injury protects neurones through recovery of the hexokinase 2-mediated glucose uptake.

Ischemic stroke, a major cause of death, is caused by occlusion of a blood vessel, resulting in significant reduction in regional cerebral blood flow. MiRNAs are a family of short noncoding RNAs (18-22 nts) and bind the 3'-UTR of their target genes to suppress the gene expression post-transcriptionally. In the present study, we report that miR-143 is down-regulated in rat neurones but highly expressed in astrocytes. In vivo middle cerebral artery occlusion (MCAO) and ex vivo oxygen-glucose deprivation (OGD) results showed that miR-143 was significantly induced by ischemia injury. Meanwhile, we observed suppression of glucose uptake and lactate product of rat brain and primary neurones after MCAO or OGD. The glycolysis enzymes hexokinase 2 (HK2), PKM2, and LDHA were inhibited by MCAO or OGD at protein and mRNA levels. In addition, overexpression of miR-143 significantly inhibited HK2 expression, glucose uptake, and lactate product. We report that HK2 is a direct target of miR-143. Importantly, restoration of HK2 in miR-143 overexpressing rat neurones recovered glucose uptake and lactate product. Our results demonstrated inhibition of miR-143 during OGD could protect rat neuronal cells from ischemic brain injury (IBI). In summary, the present study reveals a miRNA-mediated neuron protection during IBI, providing a new strategy for the development of therapeutic agents against IBI.

TNF-Alpha in Peripheral Neuropathy Patients with Impaired Glucose Regulation.

Impaired glucose regulation (IGR) is the prestate of diabetes; about 1/3 of IGR patients will develop to diabetes finally. In this study, we investigated the serum tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels in peripheral neuropathy impaired patients with impaired glucose regulation (IGR). A total of 70 IGR patients received the conventional nerve conduction test, including 30 patients with peripheral neuropathy (PN) and 40 patients without peripheral neuropathy (NPN). The other 40 healthy individuals were recruited as controls. The serum TNF-α and IL-6 in IGR patients were higher than in control group, and serum TNF-α and IL-6 levels in IGR-PN group were higher than in IGR-NPN group (27.7 ± 17.8 versus 13.1 ± 6.7 pg/mL and 18.1 ± 17.7 versus 6.4 ± 3.7 pg/mL, resp., both p < 0.05). Multifactors logistic regression analysis showed that TNF-α (OR = 0.893; p = 0.009) was an independent factor affecting whether IGR could combine with peripheral neuropathy. TNF-α and IL-6 could aggregate peripheral neuropathy in impaired glucose regulation patients; TNF-α might be independent risk factor for peripheral neuropathy in glucose regulation impaired patients.

Absence of split hand in the flail arm variant of ALS.

Flail arm syndrome (FAS), a variant of amyotrophic lateral sclerosis (ALS), has many similarities with upper limb onset ALS (UL-ALS). This study analyzed the compound muscle action potentials (CMAPs) recorded from abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles in patients presenting these two types of ALS variants, compared to normal controls. The APB/ADM CMAP amplitude ratio was lower in the UL-ALS group (mean±SEM: 0.56±0.37), consistent with a split hand, compared to the FAS (1.05±0.29) or control (1.11±0.30) groups. An abnormally reduced APB/ADM CMAP amplitude ratio (<0.6) was found in 40% of UL-ALS patients and 11% of FAS patients. However, absent CMAP in the APB or extremely low APB/ADM CMAP amplitude ratio (<0.25) were observed only in UL-ALS patients (27%) and could be used as diagnostic criteria to differentiate UL-ALS from FAS variant.

Neuroprotection against vascular dementia after acupuncture combined with donepezil hydrochloride: P300 event related potential.

Acupuncture can be used to treat various nervous system diseases. Here, 168 vascular dementia patients were orally administered donepezil hydrochloride alone (5 mg/day, once a day for 56 days), or combined with acupuncture at Shenting (DU24), Tianzhu (BL10), Sishencong (Extra), Yintang (Extra), Renzhong (DU26), Neiguan (PC6), Shenmen (HT7), Fengchi (GB20), Wangu (GB12) and Baihui (DU20) (once a day for 56 days). Compared with donepezil hydrochloride alone, P300 event related potential latency was shorter with an increased amplitude in patients treated with donepezil hydrochloride and acupuncture. Mini-Mental State Examination score was also higher. Moreover, these differences in P300 latency were identified within different infarcted regions in patients treated with donepezil hydrochloride and acupuncture. These findings indicate that acupuncture combined with donepezil hydrochloride noticeably improves cognitive function in patients with vascular dementia, and exerts neuroprotective effects against vascular dementia.

Sensory Guillain-Barré syndrome: A case report.

A 58-year-old female exhibited the onset of symmetrical sensory abnormalities of the face and extremities. The neurological examination revealed normal muscle strength with abated or absent tendon reflexes. The patient experienced symmetrical glove- and stocking-type pinprick sensations in the distal extremities and a loss of temperature sensation, but had normal proprioception and vibration senses and joint topesthesia. The lumbar puncture showed protein cell separation at the fifth week after the onset of symptoms. At the same time-point, the electrophysiological examination showed demyelination changes involving the trigeminal nerve and the somatic motor nerve. Needle electromyography revealed normal results. The clinical symptoms ceased progression at the fourth week after symptom onset, and began to improve from the sixth. This case was considered to be sensory Guillain-Barré syndrome, which was characterized by its cranial nerve involvement.