Mechanisms of ferroptosis in Alzheimer's disease and therapeutic effects of natural plant products: A review.

Neurodegenerative diseases, such as Alzheimer's disease (AD), are characterized by massive loss of specific neurons. It is a progressive disabling, severe and fatal complex disease. Due to its complex pathogenesis and limitations of clinical treatment strategies, it poses a serious medical challenge and medical burden worldwide. The pathogenesis of AD is not clear, and its potential biological mechanisms include aggregation of soluble amyloid to form insoluble amyloid plaques, abnormal phosphorylation of tau protein and formation of intracellular neurofibrillary tangles (NFT), neuroinflammation, ferroptosis, oxidative stress and metal ion disorders. Among them, ferroptosis is a newly discovered programmed cell death induced by iron-dependent lipid peroxidation and reactive oxygen species. Recent studies have shown that ferroptosis is closely related to AD, but the mechanism remains unclear. It may be induced by iron metabolism, amino acid metabolism and lipid metabolism affecting the accumulation of iron ions. Some iron chelating agents (deferoxamine, deferiprone), chloroiodohydroxyquine and its derivatives, antioxidants (vitamin E, lipoic acid, selenium), chloroiodohydroxyquine and its derivatives Fer-1, tet, etc. have been shown in animal studies to be effective in AD and exert neuroprotective effects. This review summarizes the mechanism of ferroptosis in AD and the regulation of natural plant products on ferroptosis in AD, in order to provide reference information for future research on the development of ferroptosis inhibitors.

[Effect and safety of double plasma molecular absorption in treatment of patients with severe wasp stings injury: a multicenter historical cohort study].

OBJECTIVE: To compare the effect and safety of continuous veno-venous hemofiltration (CVVH)+double plasma molecular absorption (DPMA)+hemoperfusion (HP), CVVH+HP, and CVVH+plasma exchange (PE) in treatment of patient with severe wasp stings injury. METHODS: Multicenter, historical cohort study and superiority test were used. From July 2020 to October 2022, patients with wasp sting injury and multiple organ damage admitted to the intensive care units (ICU) of five hospitals were consecutively screened and recruited into the CVVH+DPMA+HP group (intervention group). Propensity score matching was used to establish historical cohorts. Patients with severe wasp sting injury who hospitalized from January 2016 to June 2020 in each ICU were collected and matched 1:1 with the intervention group, and divided into CVVH+HP group and CVVH+PE group according to their actual hemopurification protocols (historical control groups). The primary outcome was the acute physiology and chronic health evaluation II (APACHE II) score on days 3 and 7 after initiation of treatment. Secondary outcomes included complications, length of ICU and hospital stays, and all-cause mortality. Multivariate Cox proportional risk regression was used to analyze the prognosis of patients. RESULTS: After propensity score matching, 56 patients in intervention group and each of the two historical control groups were matched successfully. There were no significant differences in age, gender, comorbidities, biochemical test indices and critical illness scores among the groups. After treatment, APACHE II score markedly declined in all groups, and the decrease was faster in the intervention group; treatment with DPMA [hazard ratio (HR) = 1.04, 95% confidence interval (95%CI) was 1.02-1.08, P = 0.00], the decreased levels of body temperature (HR = 1.02, 95%CI was 1.00-1.03, P = 0.02), serum creatine kinase (CK; HR = 0.98, 95%CI was 0.96-1.00, P = 0.05) and myoglobin (MYO; HR = 2.88, 95%CI was 1.24-6.69, P = 0.01) were independent risk factors for APACHE II score decline to the target value (15 scores). There were no significant differences in the incidence of bleeding complications, filter or perfusion thrombosis, blood pressure reduction, catheter-related infection and anaphylaxis among the groups. CONCLUSIONS: CVVH+DPMA+HP regimen can significantly reduce the APACHE II score of patients with severe wasp sting injury, and the efficacy is superior to CVVH+HP and CVVH+PE regimens, with safety.

A Nested Case-Control Study of the Relationship between Salivary Inflammatory Mediators, Periodontal Parameters, and Preterm Birth in a Chinese Population.

Background: To explore whether salivary inflammatory mediators and periodontal indices at different gestational stages can be taken as indicators of preterm birth (PTB). Methods: This nested case-control study enrolled systemically healthy pregnant women at 9 to 36 weeks of gestation. Periodontal indices were measured at the enrollment date, and interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor (TNF-α), prostaglandin E2 (PGE2), and 8-hydroxy-deoxyguanosine (8-OHdG) in the saliva were determined by enzyme-linked immunosorbent assay (ELISA). The birth outcome was recorded. Results: PTB occurred in 26 women. A total of 104 matched women with full-term birth (FTB) were used as controls. The PTB women enrolled at 24-28 gestational weeks displayed a significantly greater bleeding index (BI), probing pocket depth (PD), PD ≥ 4 mm sites (%), saliva-TNF-α, and saliva-PGE2 (P < 0.05). BI and PGE2 in the saliva were found to be positively associated with PTB (OR = 4.79, P = 0.048, 95%CI = 1.014 to 22.628; OR = 1.07, P = 0.04, 95%CI = 1.004 to 1.135, respectively). The areas under the receiver operating characteristic curve (ROC) of BI and saliva-PGE2 were 0.82 and 0.78, respectively, and that of the combined detection was 0.91, which was larger than either marker alone, although the differences were not significant (P > 0.05). Conclusions: The combination of BI and PGE2 in saliva at 24-28 gestational weeks could be a predictor of PTB in asymptomatic women. However, the results should be further explored with larger sample size.

Beam quality measurement of high power laser by using an involute pinhole array.

A novel method for power-in-the-bucket (PIB) measurement of high power laser beams is proposed. The laser beam spot was first sampled by a rotating involute pinhole array and then collected by using a photodetector placed behind the pinholes. The spatial-temporal distribution and calibrated PIB curve of the laser beam can be obtained. The spatial and temporal resolution is 20 µm and 5 ms, respectively. Compared with conventional methods, the proposed measurement method is simple, convenient, and accurate, which is suitable for high power laser beams with jitter.

Association between periodontal indexes and biomarkers in gingival crevicular fluid and preterm birth in pregnancy: a nested case-control study.

OBJECTIVES: This study aimed to investigate the association between periodontal indexes and biomarkers in gingival crevicular fluid (GCF) and preterm birth (PTB) in pregnancy, as well as to assess the clinical value of these indexes as predictors of PTB. METHODS: A nested case-control study was conducted. A total of 300 systematically healthy pregnant women were selected within 36 weeks of gestation and grouped according to the enrolled weeks. Periodontal indexes, including probing depth (PD), bleeding index (BI), gingival index (GI), and five biomarkers in GCF, including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and 8-hydroxy-2-deoxyguanosine (8-OHdG) were measured at the enrolled date. The detailed birth outcome was recorded. RESULTS: Only women at 24-28 weeks of gestation per PTB case (four full-term births) were selected as controls subjects, PTB displayed significantly greater GI, BI, and 8-OHdG (P<0.05). Logistic regression analysis revealed that BI and 8-OHdG were the dependent risk factors of PTB (OR=5.90, P=0.034; OR=1.18, P=0.045, respectively). The areas under the receiver operating characteristic curve (ROC) of BI and 8-OHdG were 0.80 and 0.69, and that of the combined detection was 0.82, which was larger than the individual detection, although the differences were not significant (P>0.05). CONCLUSIONS: Increased BI and 8-OHdG at 24-28 weeks of gestation are risk factors for PTB. Their combined detection may have some value in the prediction of PTB, but further studies with a larger sample size are needed to explore it and thus provide experiment evidence for establishing an early warning system for PTB in pregnant women with periodontal disease.

Silicon nitride/titanium oxide hybrid waveguide design enabling broadband athermal operation.

This paper presents a special design of a new kind of silicon nitride/titanium oxide hybrid waveguide with multi-layer materials laminate structure aiming at broadband athermal operation. By incorporating three layers of titanium oxide whose thermo-optic coefficient (TOC) is negative in the waveguide core and upper cladding regions, the thermal drift of the conventional strip waveguide induced by the positive TOC of silicon nitride is fully compensated, with the effective TOC of the hybrid waveguide achieving zero at 1550 nm and only varying extremely slightly within ±6×10-7/K in the wavelength band from 1350 to 1850 nm. In addition, due to the inherent alternate growth manner of titanium dioxide and silicon nitride thin layers, this new kind of multi-layer material laminate structure waveguide holds the potential of avoiding the challenging growth of low-stress crack-free single-layer silicon nitride film thick enough for realizing an anomalous dispersion waveguide. Furthermore, we numerically demonstrate the different influences of the temperature change on optical frequency comb generation between the traditional waveguide and the hybrid waveguide, and we find that the athermal hybrid waveguide is much more temperature insensitive than the strip waveguide.

Investigation of the local dispersion change in anomalous dispersion microcavity and quantitative analysis of the phase-matching in Kerr comb generation.

We numerically simulate Kerr comb generation in an anomalous dispersion microcavity by modal expansion method and demonstrate that the initiation of comb generation is affected by the change of local dispersion possibly caused by avoided mode crossings. We also quantitatively analyze the instantaneous phase matching of different modes and reveal the characteristics of energy distribution in different modes in the dynamics of comb generation. We demonstrate that the local dispersion change can control the Kerr comb to transform between Type I and Type II combs. We also find that local dispersion is closely related to the stability of the power of Kerr comb lines, something that can change the dynamical state of the system near the Hamiltonian-Hopf bifurcation under an anomalous dispersion regime from a quasi-periodic oscillation state to a periodic state (Turing patterns).

Design of a polymer-filled silicon nitride strip/slot asymmetric hybrid waveguide for realizing both flat dispersion and athermal operation.

An asymmetric strip/slot hybrid silicon nitride waveguide is designed to simultaneously realize athermal operation and flat dispersion. The slot filling and upper cladding materials are negative thermal-optical coefficient (TOC), low refractive index polyurethane acrylate, while the left and right cladding layers are positive TOC, high refractive index silicon nitride. With suitable waveguide parameter selection, an optimum strip/slot hybrid silicon nitride waveguide exhibits an effective TOC of 1.263×10-7/K at 1550 nm, flattened dispersion in the wavelength range from 1200 to 1800 nm with the maximum dispersion of 30.51 ps/(nm·km), and a minimum of 10.89 ps/(nm·km). The proposed hybrid waveguide has great potential in building up broadband athermal microresonator optical frequency combs.

Sex Hormones Enhance Gingival Inflammation without Affecting IL-1ß and TNF-α in Periodontally Healthy Women during Pregnancy.

Hormones (progesterone and estradiol) change greatly during pregnancy; however, the mechanism of hormonal changes on gingival inflammation is still unclear. This study is to evaluate the effects of hormonal changes during pregnancy on gingival inflammation and interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in gingival crevicular fluid (GCF). 30 periodontally healthy pregnant women were evaluated in the first, second, and third trimesters. 20 periodontally healthy nonpregnant women were evaluated twice (once per subsequent month). Clinical parameters including probing pocket depth (PPD), bleeding index (BI), gingival index (GI), clinical attachment level (CAL), and plaque index (PLI) were recorded. GCF levels of IL-1ß and TNF-α and serum levels of progesterone and estradiol were measured. From the data, despite low PLI, BI and GI increased significantly during pregnancy; however, no significant changes in PLI, CAL, IL-1ß, or TNF-α GCF levels were observed. Although IL-1ß, not TNF-α, was higher in pregnant group than in nonpregnant group, they showed no correlation with serum hormone levels during pregnancy. GI and BI showed significant positive correlation with serum hormone levels during pregnancy. This study suggests that sex hormone increase during pregnancy might have an effect on inflammatory status of gingiva, independent of IL-1ß and TNF-α in GCF.

Influence of connection type on the biomechanical behavior of distal extension mandibular removable partial dentures supported by implants and natural teeth.

Few studies are performed to evaluate the influence of connection type on the stress distribution of distal extension mandibular removable partial dentures (RPDs) supported by both implants and natural teeth. In this study, five three-dimensional finite element models were prepared to simulate mandibular bilateral partially edentulous arches. Four were RPDs supported by both implants and natural teeth, and the other one was RPDs supported only by natural teeth. The maximum equivalent (EQV) stress values of bone around implants, the abutments, and the mucosa displacements of the related supporting structures were measured. It was found that a non-rigid telescopic coping was more favorable to protect the implant than a rigid telescopic coping. Compared with other connection types, the easy resilient attachment (ERA) system seemed to be effective to associate implant without complications. However, the results obtained in the present study should be cautiously interpreted in the clinic.

Relationship between gingival inflammation and pregnancy.

An increase in the prevalence and severity of gingival inflammation during pregnancy has been reported since the 1960s. Though the etiology is not fully known, it is believed that increasing plasma sex steroid hormone levels during pregnancy have a dramatic effect on the periodontium. Current works of research have shown that estrogen and progesterone increasing during pregnancy are supposed to be responsible for gingivitis progression. This review is focused not only on epidemiological studies, but also on the effects of progesterone and estrogen on the change of subgingival microbiota and immunologic physiological mediators in periodontal tissue (gingiva and periodontal ligament), which provides current information about the effects of pregnancy on gingival inflammation.

Theoretical role of adjunctive implant positional support in stress distribution of distal-extension mandibular removable partial dentures.

This preliminary study evaluated the adjunctive supporting role of diverse implant positions on stress distribution in a Class I removable partial denture (RPD) design. Nine three-dimensional finite element models were prepared to simulate mandibular RPD designs with three different loading conditions applied. Implant supported designs demonstrated lower stress value concentrations and mucosal displacement.

Design of a silicon Mach-Zehnder modulator with a U-type PN junction.

We have developed a silicon depletion-mode modulator featuring a novel U-type PN junction that enables a substantial improvement in electro-optical modulation efficiency. Through electrical, optical, and manufacturing process simulations, an ultralow VπL of 0.63 V·cm is exhibited with 3 V reverse bias. The high modulation efficiency enables a high extinction ratio (ER) of >17 dB with only a 1 mm phase shifter when the excess loss at the "on" state is 2 dB. The ER can maintain >12 dB at ∼28 GHz operation with a 3 V peak-to-peak voltage due to the small voltage attenuation of the short phase shifter.

Ultra-compact and fabrication-tolerant polarization rotator based on a bend asymmetric-slab waveguide.

We propose and analyze a polarization rotator based on a bend asymmetric-slab waveguide on the silicon-on-insulator platform. The device can be fabricated using standard complementary metal-oxide-semiconductor process involving only two dry etching steps. Compared with the formerly reported polarization rotators based on two-step etching, our introduced device demonstrates a significant improvement for fabrication tolerance. Furthermore, an ultra compact structure of ~5 µm conversion length, an insertion loss of only 0.5 dB, and an extinction ratio of >40 dB for both TE to TM polarization conversion and TM to TE polarization conversion are exhibited. Operation wavelength and the influence of environmental temperature on our device are also discussed.

Ultracompact polarization splitter-rotator based on an asymmetric directional coupler.

An ultracompact polarization splitter-rotator based on an asymmetric directional coupler has been designed and analyzed. The device consists of one channel waveguide and one vertical slot waveguide, which couple to each other to form the asymmetric directional coupler. The coupling length is only 17.4 µm, and the polarization extinction ratio, with its largest value of 18 dB, is more than 15 dB in the operating wavelength range from 1515 to 1560 nm. The TM-to-TE conversion efficiency can reach up to 95% (0.02 dB) at 1550 nm wavelength.

Bistability and self-pulsation phenomena in silicon microring resonators based on nonlinear optical effects.

Bistability (BS) and self-pulsation (SP) phenomena in silicon microring resonators (MRR) with intense CW light injection are studied. Several nonlinear optical effects including Kerr effect, two-photon absorption, free carrier absorption and free carrier dispersion are taken into account. The threshold optical intensity of BS and SP is derived from the coupled mode theory and a linear stability analysis method. The influences of MRR's parameters (carrier lifetime, linear loss and radius) and light injection conditions (input power, wavelength detuning) on the characteristics of SP (modulation depth and oscillating frequency) are analyzed and discussed. It is shown that, SP occurs only if the carrier lifetime ranges from several ps to several-hundred ps and the input light intensity is higher than 106W/cm². The modulation depth of SP can be as large as 8dB and the associated oscillating frequency is in the range from several GHz to beyond 10 GHz.

Design and fabrication of a photonic crystal channel drop filter based on an asymmetric silicon-on-insulator slab.

We report on the design and fabrication of a photonic crystal (PC) channel drop filter based on an asymmetric silicon-on-insulator (SOI) slab. The filter is composed of two symmetric stick-shape micro-cavities between two single-line-defect (W1) waveguides in a triangular lattice, and the phase matching condition for the filter to improve the drop efficiency is satisfied by modifying the positions and radii of the air holes around the micro-cavities. A sample is then fabricated by using electron beam lithography (EBL) and inductively coupled plasma (ICP) etching processes. The measured Q factor of the filter is about 1140, and the drop efficiency is estimated to be 73% +/- 5% by fitting the transmission spectrum.

Small molecule antagonists of the CC chemokine receptor 4 (CCR4).

The identification, optimization, and structure-activity relationship (SAR) of small-molecule CCR4 antagonists is described. An initial screening hit with micromolar potency was identified that was optimized to sub-micromolar binding potency by enantiomer resolution, halogenation of the naphthalene ring, and extension of the alkyl chain linker between the central piperidine ring and the terminal aryl group. An antagonist was identified that showed good cross-reactivity against the mouse receptor and inhibited CCR4-based cell recruitment in dose-dependent fashion.

Submicrosecond rearrangeable nonblocking silicon-on-insulator thermo-optic 4x4 switch matrix.

A rearrangeable nonblocking silicon-on-insulator-based thermo-optic 4x4 switch matrix is designed and fabricated. A spot-size converter is integrated to reduce the insertion loss, and a new driving circuit is designed to improve the response speed. The insertion loss is less than 10 dB, and the response time is 950 ns.

On-line beam diagnostic method for high energy laser with large beam profile.

A novel on-line beam diagnostic method for continuous-wave high energy laser (HEL) is presented. The system based on this method is mainly consisted of a scanning circular reflector and a photodetector array disposed spatially. Laser beam passes through the system except a little part of whole beam is sampled and reflected into the detector array by the circular reflector. Through the arithmetic of spatial mapping and image restoration with the output signal of detector array, the spatial-temporal distribution parameters of the laser beam are obtained. The HEL beam of several hundred millimeters in diameter can be on-line measured with spatial resolution of 2 mm and temporal resolution of 30~50ms.